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Title
ウシ発情周期中に発育する第1卵胞波主席卵胞の生理学的
性質 ― 発育動態、機能および受胎性に及ぼす影響 ―( 本
文(Fulltext) )
Author(s)
三浦, 亮太朗
Report No.(Doctoral
Degree)
博士(獣医学) 甲第440号
Issue Date
2015-03-13
Type
博士論文
Version
ETD
URL
http://repository.lib.gifu-u.ac.jp/handle/123456789/51006
※この資料の著作権は、各資料の著者・学協会・出版社等に帰属します。
࢘ࢩⓎ᝟࿘ᮇ୰࡟Ⓨ⫱ࡍࡿ
➨ 1 ༸⬊Ἴ୺ᖍ༸⬊ࡢ⏕⌮Ꮫⓗᛶ㉁
㸫Ⓨ⫱ືែࠊᶵ⬟࠾ࡼࡧཷ⫾ᛶ࡟ཬࡰࡍᙳ㡪㸫
2014 ᖺ
ᒱ㜧኱Ꮫ኱Ꮫ㝔㐃ྜ⋇་Ꮫ◊✲⛉
㸦ᖏᗈ␆⏘኱Ꮫ㸧
୕ᾆ ுኴᮁ
┠ḟ
➨㸯❶ ⥴ゝ 1
➨㸰❶ ➨ 1 ༸⬊Ἴ୺ᖍ༸⬊㸦W1DF㸧ࡢⓎ⫱ືែ㸪᤼༸๓ᚋࡢᶵ⬟࠾ࡼࡧ᤼༸ᚋ࡟
ᙧᡂࡉࢀࡿ㯤యࡢᛶ㉁
9
2㸫1. ᗎㄽ
10
2㸫2. ヨ㦂 1㸸༸⬊ἼⓎ⌧࠿ࡽ 7 ᪥┠ࡲ࡛ࡢ W1DF ࡜ W2DF ࡢⓎ⫱ືែ࠾ࡼࡧ
10
༸⬊ቨ⾑ὶࡢẚ㍑
2㸫3. ヨ㦂 2㸸Ⓨ᝟࠾ࡼࡧ᤼༸ㄏ㉳᫬࡟࠾ࡅࡿ W1DF ࡜ W2DF ࡢⓎ⫱ືែ㸪
༸⬊ቨ⾑ὶ࠾ࡼࡧ⾑୰ E2 ⃰ᗘࡢẚ㍑
14
2㸫4. ヨ㦂 3㸸W1DF ࡜ W2DF ࡟࠾ࡅࡿ᤼༸๓ࡢ༸⬊ෆࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥ⃰ᗘ
࠾ࡼࡧ㢛⢏ᒙ⣽⬊࡛Ⓨ⌧ࡋ࡚࠸ࡿᅉᏊࡢẚ㍑ 16
2㸫5. ヨ㦂 4㸸W1DF ࡜ W2DF ࡢ᤼༸ᚋ࡟ᙧᡂࡉࢀࡿ㯤యࡢᙧែ㸪㯤య⾑ὶ
21
࠾ࡼࡧ⾑୰ P4 ⃰ᗘ᥎⛣ࡢẚ㍑
2㸫6. ⤖ᯝ 23
2㸫7. ⪃ᐹ 26
2㸫8. ᑠᣓ 32
ᅗ࣭⾲ 33
i
➨㸱❶ ➨ 1 ༸⬊Ἴ୺ᖍ༸⬊㸦W1DF㸧ࡢⓎ⫱ࢆไᚚࡍࡿせᅉ 3㸫1. ᗎㄽ
57
58
3㸫2. ヨ㦂 1㸸༸⬊ἼⓎ⌧࠿ࡽ 7 ᪥┠ࡢ W1DF ࡢ┤ᚄ࡜⾑୰ P4 ⃰ᗘࡢ┦㛵㛵ಀ
࠾ࡼࡧ W1DF ࡜㯤యࡢඹᏑࡲࡓࡣ㠀ඹᏑ㛵ಀࡀ W1DF ࡢ┤ᚄ࡟ཬࡰࡍ
58
ᙳ㡪
3㸫3. ヨ㦂 2㸸W1DF ࡜㯤యࡢඹᏑࡲࡓࡣ㠀ඹᏑ㛵ಀࡀ༸⬊ἼⓎ⌧᪥࠿ࡽ 5 ᪥┠
ࡲ࡛ࡢ W1DF ࡜㯤యࡢⓎ⫱ືែ㸪⾑୰ P4 ⃰ᗘ㸪࠾ࡼࡧ༸⬊ᾮࢫࢸࣟ࢖ࢻ࣍
ࣝࣔࣥ⃰ᗘ࡟ཬࡰࡍᙳ㡪
60
3㸫4. ⤖ᯝ
63
3㸫5. ⪃ᐹ
64
3㸫6. ᑠᣓ 66
68
ᅗ࣭⾲
➨㸲❶ 㯤య࡜ྠ୍༸ᕢෆ࡟Ꮡᅾࡍࡿ➨ 1 ༸⬊Ἴ୺ᖍ༸⬊㸦W1DF㸧ࡢᛶ㉁࠾ࡼࡧ
ཷ⫾ᛶ࡟ཬࡰࡍᙳ㡪
4㸫1. ᗎㄽ
77
78
4㸫2. ヨ㦂 1㸸Ἢங∵࡟࠾ࡅࡿ W1DF ࡜㯤యࡢඹᏑ࠾ࡼࡧ㠀ඹᏑ㛵ಀࡀ W1DF ࡜
㯤యࡢⓎ⫱ືែ࠾ࡼࡧ⾑୰ P4 ⃰ᗘ᥎⛣࡟ཬࡰࡍᙳ㡪 ii
78
4㸫3. ヨ㦂 2㸸W1DF ࡜㯤యࡢඹᏑ࠾ࡼࡧ㠀ඹᏑ㛵ಀࡀேᕤᤵ⢭ᚋࡢཷ⫾⋡࡟
ཬࡰࡍᙳ㡪 80
4㸫4. ⤖ᯝ
82
4㸫5. ⪃ᐹ
84
4㸫6.
ᑠᣓ 87
88
ᅗ࣭⾲
➨㸳❶ ⥲ྜ⪃ᐹ 92
ㅰ㎡
100
ཧ⪃ᩥ⊩
101
iii
␎ㄒ
P4㸸Progesterone㸦ࣉࣟࢪ࢙ࢫࢸࣟࣥ㸧
E2㸸Estradiol-17E㸦࢚ࢫࢺࣛࢪ࣮࢜ࣝ㸧
A4㸸Androstendion㸦࢔ࣥࢻࣟࢫࢸࣥࢪ࢜ࣥ㸧
GnRH㸸Gonadotropin releasing hormone㸦ᛶ⭢่⃭࣍ࣝࣔࣥᨺฟ࣍ࣝࣔࣥ㸧
FSH㸸Follicle stimulating hormone㸦༸⬊่⃭࣍ࣝࣔࣥ㸧
LH㸸Luteinizing hormone㸦㯤యᙧᡂ࣍ࣝࣔࣥ㸧
W1DF㸸The first follicular wave dominant follicle㸦➨ 1 ༸⬊Ἴ୺ᖍ༸⬊㸧
W2DF㸸The second follicular wave dominant follicle㸦➨ 2 ༸⬊Ἴ୺ᖍ༸⬊㸧
PG㸸Prostaglandin㸦ࣉࣟࢫࢱࢢࣛࣥࢪࣥ㸧
BFA㸸Blood flow area㸦༸⬊ቨ⾑ὶ㠃✚㸧
BF%㸸The percentage of follicle circumference with blood flow signals㸦⾑ὶศᕸ๭ྜ㸧
EIA㸸Enzyme immuno assay㸦㓝⣲ච␿ ᐃἲ㸧
BSA㸸Bovine serum albumin㸦∵⾑Ύ࢔ࣝࣈ࣑ࣥ㸧
cDNA㸸complementary DNA㸦┦⿵ⓗ DNA㸧
PCR㸸Polymerase chain reaction
LHr㸸LH receptor㸦LH ཷᐜయ㸧
CYP19A1㸸Aromatase㸦࢔࣐ࣟࢱ࣮ࢮ㸧
COX-2㸸Cyclooxygenase-2
NO㸸Nitric oxide㸦୍㓟໬❅⣲㸧
iNOS㸸Inducible nitric oxide synthase㸦ㄏᑟᆺ୍㓟໬❅⣲ྜᡂ㓝⣲㸧
eNOS㸸Endotherial nitric oxide synthase㸦⾑⟶ෆ⓶ᆺ୍㓟໬❅⣲ྜᡂ㓝⣲㸧
VEGF㸸Vascular endotherial growth factor㸦⾑⟶ෆ⓶ቑṪᅉᏊ㸧
FGF㸸Fibroblast growth factor㸦⥺⥔ⱆ⣽⬊ቑṪᅉᏊ㸧
iv
StAR㸸Steroidogenic acute regulatory protein
P450-scc㸸Cytochrome P450 side chain cleavage enzyme㸦ࢳࢺࢡ࣮࣒ࣟ P450 ഃ㙐ษ᩿㓝⣲㸧
3E-HSD㸸3E-hydroxysteroid dehydrogenase㸦3E-Ỉ㓟ᇶ⬺Ỉ⣲㓝⣲㸧
GAPDH㸸Glyceraldehyde-3-phosphate dehydrogenase㸦ࢢࣜࢭࣝ࢔ࣝࢹࣄࢻ 3 ࣜࣥ㓟⬺Ỉ⣲㓝⣲㸧
W1CL㸸Corpus luteum formed after ovulation of W1DF㸦W1DF ᤼༸ᚋ㯤య㸧
W2CL㸸Corpus luteum formed after ovulation of W2DF㸦W2DF ᤼༸ᚋ㯤య㸧
TMR㸸Total mixed ration
BCS㸸Body condition score㸦࣎ࢹ࢕࣭ࢥࣥࢹ࢕ࢩ࣭ࣙࣥࢫࢥ࢔㸧
v
➨㸯❶
⥴ゝ
1
࢘ࢩࡢᐙ␆໬ࡣ⣙ 9,000 ᖺ๓࠿ࡽ㛤ጞࡋࡓ࡜⪃࠼ࡽࢀ࡚࠾ࡾ㸪ᆅ⌫ୖࡢ࠸ࡓࡿ࡜ࡇࢁ
࡟⏕ᜥࡋ࡚࠸ࡓཎ∵㸦࣮࢜ࣟࢵࢡࢫ㸪Bos primigenius㸧ࢆᇶ࡟ࡋ࡚㸪す࢔ࢪ࢔ᆅᇦࢆ୰ᚰ
࡟ᐙ␆໬ࡀ㐍⾜ࡋࡓ࡜ࡉࢀࡿࠋึᮇ࡟࠾࠸࡚㸪࢘ࢩࡣ⫗ࡢ฼⏝ࡸ᐀ᩍⓗ൤ᘧ࡟⏝࠸ࡿࡇ
࡜ࢆ┠ⓗ࡟ᐙ␆໬ࡉࢀ㸪ࡑࡢᚋࡣ㎰⪔࡟࠾࠸࡚ࡶᚲせ୙ྍḞ࡞ᐙ␆࡜࡞ࡗ࡚࠸ࡗࡓࠋࡋ
࠿ࡋ࡞ࡀࡽ㸪ྂ௦㑇㊧࠿ࡽⓎぢࡉࢀࡿ㔝⏕ື≀ࡢ㦵ࡀ࢘ࢩࡢᐙ␆໬ࢆቃ࡟ࡋ࡚ῶᑡࡍࡿ
ࡇ࡜࠿ࡽ㸪ᐙ␆࢘ࢩࡢ୺せ࡞┠ⓗࡀ㣗ᩱࢆ☜ಖࡍࡿࡓࡵ࡛࠶ࡗࡓ࡜⪃࠼ࡽࢀ࡚࠸ࡿࠋFAO
ࡢ 2007 ᖺࡢ⤫ィ࡟ࡼࢀࡤ㸪
ୡ⏺࡛㣫⫱ࡉࢀ࡚࠸ࡿ࢘ࢩࡢ㢌ᩘࡣ 13 ൨ 6,000 ୓㢌࡛࠶ࡾ㸪
ࡑࡢศᕸࡣ࢔ࢪ࢔ᆅᇦ࡟ 31㸣㸪୰ኸ࠾ࡼࡧ༡࢔࣓ࣜ࢝ᆅᇦ࡟ 29㸣㸪࢔ࣇࣜ࢝࡟ 19㸣㸪
࣮ࣚࣟࢵࣃ࡟ 10㸣㸪໭࢔࣓ࣜ࢝࡟ 8㸣㸪࢜ࢭ࢔ࢽ࢔࡟ 3㸣࡜࡞ࡗ࡚࠸ࡿࠋᅜ༢఩࡛ࡣࣈ
ࣛࢪࣝ࡟ 2 ൨㢌㸪࢖ࣥࢻ࡟ 1 ൨ 8,000 ୓㢌㸪࢔࣓ࣜ࢝ྜ⾗ᅜ࡟ 9,700 ୓㢌㸪୰ᅜ࡟ 8,200
୓㢌㸪࢔ࣝࢮࣥࢳࣥࡀ 5,100 ୓㢌࡜⥆ࡁ㸪᪥ᮏ࡟ࡣ 440 ୓㢌ࡀᏑᅾࡍࡿࠋࡇࡢࡼ࠺࡟ୡ
⏺୰࡛ከࡃ㣫㣴ࡉࢀ࡚࠸ࡿ࢘ࢩ࠿ࡽ㸪⫗㸪⏕ஙࡉࡽ࡟ຍᕤங〇ရ࡞࡝ࡀ⏕⏘ࡉࢀ㸪࢘ࢩ
ࡣ⌧௦࡟࠾࠸࡚᭱ࡶ㔜せ࡞ᐙ␆ࡢ୍ࡘ࡛࠶ࡿ࡜ࡉࢀ࡚࠸ࡿࠋ
᪥ᮏ࡟࠾ࡅࡿᐙ␆࡜ࡋ࡚ࡢ࢘ࢩࡢከࡃࡣ㸪⫗⏕⏘ࢆ⾜࠺⫗⏝∵㸪࠶ࡿ࠸ࡣ⏕ஙࡸங〇
ရࢆ〇㐀ࡍࡿࡓࡵࡢஙࢆ⏕⏘ࡍࡿங⏝∵࡜ࡋ࡚㣫㣴ࡉࢀ࡚࠸ࡿࠋ⫗⏝∵ࡢ⏕⏘ࡢࡓࡵ㸪
ࡲࡓங⏝∵ࡀἪஙࡋங⏕⏘ࢆ࠾ࡇ࡞࠺ࡓࡵ࡟ࡣ㸪㞤∵ࡀཷ⫾ࡋศፔࡍࡿᚲせࡀ࠶ࡾ㸪␆
⏘ᴗࡀ⤒῭ⓗ࡟ᡂ❧ࡍࡿࡓࡵ࡟ࡣ㸪㞤∵ࡀຠ⋡ⓗ࡟㡰ㄪ࡞ࢧ࢖ࢡ࡛ࣝཷ⫾ࡋศፔࡋ࡚࠸
ࡃᚲせࡀ࠶ࡿࠋ
㏆ᖺ㸪᪥ᮏࢆྵࡴඛ㐍ㅖᅜ࡛ࡣ␆⏘㎰ᐙ㸪≉࡟㓗㎰ᐙ 1 ᡞᙜࡓࡾࡢ㣫㣴㢌ᩘࡀቑຍࡋ
࡚࠸ࡿࠋ᪥ᮏࢆ౛࡟࠶ࡆࡿ࡜㸪1 ᡞᙜࡓࡾࡢங∵㣫㣴㢌ᩘࡣ 1960 ᖺ࡟ࡣ 2.0 㢌࡛࠶ࡗࡓ
ࡢ࡟ᑐࡋ࡚㸪1980 ᖺ࡟ࡣ 18.1 㢌㸪1990 ᖺ࡟ࡣ 32.5 㢌㸪2000 ᖺ࡟ࡣ 52.5 㢌ࡑࡋ࡚ 2012
ᖺ࡟ࡣ 72.1 㢌࡜࡞ࡾ㸪ࡇࡢ 50 ᖺ࡛ᛴ⃭࡞㣫㣴つᶍᣑ኱ࡀࡳࡽࢀࡿ㸦␆⏘⤫ィㄪᰝ㸪㎰
ᯘỈ⏘┬㸧
ࠋࡲࡓ㸪࢘ࢩࡢ㑇ఏᨵⰋࡸ㣫㣴⟶⌮ᢏ⾡ࡢྥୖ࡟ࡼࡾ㸪ங⏝∵ࡢಶయங㔞ࡣ඲
ୡ⏺ⓗ࡟ቑຍഴྥ࡟࠶ࡿࠋ࢔࣓ࣜ࢝ྜ⾗ᅜ࡛ࡣ 1951 ᖺ࠿ࡽ 1996 ᖺ࡟࠿ࡅ࡚ 5,000 kg ࠿
2
ࡽ 9,000 kg ௨ୖ࡬࡜ᖺ㛫ᖹᆒಶయங㔞ࡀቑຍࡋ࡚࠸ࡿ㸦18㸧
ࠋ᪥ᮏ࡟࠾ࡅࡿங⏝∵ࡢᖺ㛫
ᖹᆒಶయங㔞ࡣ㸪1975 ᖺ࡟ࡣ 5,826 kg ࡛࠶ࡗࡓࡢ࡟ᑐࡋ࡚㸪1980 ᖺ࡟ࡣ 6,339 kg㸪1990
ᖺ࡟ࡣ 7,798 kg㸪2000 ᖺ࡟ࡣ 8,794 kg ࡑࡋ࡚ 2010 ᖺ࡟ࡣ 9,286 kg ࡜࡞ࡾⴭࡋࡃቑຍࡋ࡚
࠸ࡿ㸦ங⏝∵⩌⬟ຊ᳨ᐃᡂ⦼ࡢࡲ࡜ࡵ㸫ᖹᡂ 24 ᖺᗘ㸫㸪ᐙ␆ᨵⰋ஦ᴗᅋ㸧
ࠋࡲࡓ㸪⫗⏝
∵࡟࠾࠸࡚ࡶ 1 ᡞᙜࡓࡾࡢ㣫㣴㢌ᩘࡣ 1960 ᖺ࡛ࡣ 1.2 㢌࡛࠶ࡗࡓࡢ࡟ᑐࡋ࡚㸪1980 ᖺ࡟
ࡣ 5.9 㢌㸪1990 ᖺ࡟ࡣ 11.6 㢌㸪2000 ᖺ࡟ࡣ 24.2 㢌ࡑࡋ࡚ 2012 ᖺ࡟ࡣ 41.8 㢌࡜࡞ࡾ㸪ங
⏝∵࡜ྠᵝ࡟㣫㣴つᶍᣑ኱ࡀぢཷࡅࡽࢀࡿ㸦␆⏘⤫ィㄪᰝ㸪㎰ᯘỈ⏘┬㸧
ࠋ
⌧௦࡟࠾࠸࡚㸪ከࡃࡢ㞤∵ࡣேᕤᤵ⢭࡟ࡼࡾཷ⫾㸪ศፔࡋ࡚࠸ࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠾ࡾ㸪
ேᕤᤵ⢭ࡢᬑཬ⋡࡟㛵ࡋ࡚ࡣ㸪࢔࣓ࣜ࢝ྜ⾗ᅜ࡛ࡣங⏝∵ࡢ 72㸣㸦92㸧
㸪᪥ᮏ࡛ࡣங⏝
∵㸪⫗⏝∵࡜ࡶ࡟ 95㸣௨ୖ㸦44㸧࡜࡞ࡗ࡚࠸ࡿࠋࡇࡢࡓࡵ㸪ຠ⋡ⓗ࠿ࡘ㐺ษ࡞㞤∵ࡢⓎ
᝟Ⓨぢࡀ⦾Ṫᡂ⦼ྥୖࡢ㔜せ࡞せᅉ࡜࡞ࡗ࡚࠸ࡿࠋࡋ࠿ࡋ࡞ࡀࡽ㸪ᛴ⃭࡞㣫㣴つᶍࡢᣑ
኱࡟క࠺㸪Ⓨ᝟Ⓨぢ⋡ࡢపୗࡀ✵⫾ᮇ㛫ࡢᘏ㛗࡟ࡘ࡞ࡀࡾ㸪⦾Ṫᡂ⦼ࡢపୗࢆࡶࡓࡽࡋ
࡚࠸ࡿࠋࡲࡓ㸪ங⏝∵࡟㛵ࡋ࡚ࡣ㧗Ἢங໬࡟క࠸㸪⫢⮚࡛ࡢࢫࢸࣟ࢖ࢻ௦ㅰஹ㐍㸦100㸧
ࡀᣦ᦬ࡉࢀ࡚࠾ࡾ㸪ࡑࢀ࡟క࠺Ⓨ᝟ᚤᙅ໬࠾ࡼࡧⓎ᝟Ⓨ⌧᫬㛫ࡢ▷⦰㸦55㸧࡟㉳ᅉࡍࡿ
Ⓨ᝟Ⓨぢ⋡࡞࡝ࡢపୗࡸ㸪㐺ᮇᤵ⢭ࡀᐇ᪋࡛ࡁ࡞࠸ࡇ࡜࡟ࡼࡿཷ⫾ᛶࡢపୗࡀ኱ࡁ࡞ၥ
㢟࡜࡞ࡗ࡚࠸ࡿࠋ
ࡑࡢࡓࡵ㸪࢔࣓ࣜ࢝ྜ⾗ᅜࢆ୰ᚰ࡜ࡋࡓඛ㐍ᅜ࡛ࡣ㸪⦾Ṫᡂ⦼ྥୖࢆ┠ⓗ࡟ྛ✀࣍ࣝ
ࣔࣥ〇๣ࢆ⏝࠸࡚㸪࢜ࣈࢩࣥࢡἲ㸦72㸧࡞࡝Ⓨ᝟Ⓨぢࢆᚲせ࡜ࡋ࡞࠸ᐃ᫬ேᕤᤵ⢭ࣉࣟ
ࢢ࣒ࣛࡢ㛤Ⓨ࡜ᨵⰋࢆ⾜ࡗ࡚ࡁࡓ㸦32㸪50㸪60㸪77㸪90㸧
ࠋࡋ࠿ࡋ࡞ࡀࡽ㸪ࡇࢀࡽࡢࣉࣟ
ࢢ࣒ࣛࢆ⏝࠸ࡿࡇ࡜࡛㸪ᤵ⢭⋡ࢆྥୖࡉࡏࡿࡇ࡜࡟ࡣᡂຌࡋࡓࡀ㸪ཷ⫾⋡ࡢྥୖ࡟㛵ࡋ
࡚ࡣ⌧ᅾ࡟⮳ࡿࡲ࡛࡟༑ศ࡟㐩ᡂ࡛ࡁ࡚࠸࡞࠸ࠋࡇࡢࡇ࡜ࡣ㸪࢘ࢩࡢ⦾Ṫ⏕⌮࡟ᑐࡍࡿ
⌮ゎࡸ㸪ዷፎᡂ❧࡟㛵ࢃࡿせᅉࡢゎ᫂ࡉࡽ࡟ࡣཷ⫾⋡ࡢྥୖࢆࡶࡓࡽࡍෆศἪ≧ែࢆస
ฟࡍࡿᤵ⢭ࣉࣟࢢ࣒ࣛࡢ㛤Ⓨࡀ☜❧ࡋ࡚࠸࡞࠸ࡇ࡜ࢆ♧၀ࡋ࡚࠸ࡿࠋࡑࡢࡓࡵ㸪࢘ࢩࡢ
⦾Ṫ⏕⌮࡟ᑐࡋ࡚௒ࡲ࡛ὀ┠ࡉࢀ࡚࠸࡞࠿ࡗࡓⅬ࡟ࡘ࠸࡚ࡢᇶ♏ⓗ࡞ㄪᰝࡸ◊✲ࢆ⾜ࡗ
3
࡚࠸ࡃᚲせࡀ࠶ࡿࠋ
㞤ࡀ஺㓄ࡢࡓࡵ࡟㞝ࢆチᐜࡍࡿ≧ែࡀⓎ᝟࡜ᐃ⩏ࡉࢀ㸪ࡇࡢⓎ᝟ࡣ࿘ᮇⓗ࡟⧞ࡾ㏉ࡉ
ࢀ࡚࠾ࡾ㸪ࡇࡢ࿘ᮇࢆⓎ᝟࿘ᮇ࡜࠸࠺ࠋ࢘ࢩࡣ࿘ᖺ⦾ṪࡢከⓎ᝟ື≀࡛࠶ࡾ㸪6㹼12 ࣧ
᭶㱋࡛ᛶᡂ⇍࡟㐩ࡋࡓᚋ㸦30㸧
㸪ዷፎࡋ࡞࠸㝈ࡾ 1 ᖺࢆ㏻ࡋ࡚࿘ᮇⓗ࡟Ⓨ᝟ࢆ⧞ࡾ㏉ࡍࡼ
࠺࡟࡞ࡿࠋⓎ᝟࿘ᮇ୰࡟ࡣ༸ᕢෆᵓ㐀≀࡛࠶ࡿ㯤య࡜༸⬊ࡢⓎ⫱࡜㛢㙐࣭㏥⾜ࡢ࿘ᮇⓗ
ኚ໬ࡀࡳࡽࢀࡿࠋ࢘ࢩࡢⓎ᝟࿘ᮇࡢᖹᆒ᪥ᩘࡣ 21 ᪥࡛࠶ࡿ㸦30㸧ࡀ㸪Ⓨ᝟࿘ᮇࡢ᪥ᩘ࡟
ࡣ 18㹼24 ᪥࡜ᖜࡢ࠶ࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿ㸦30㸧
ࠋⓎ᝟࿘ᮇࡣ኱ࡁࡃ㯤యᮇ㸦14㹼18 ᪥
㛫㸧࡜༸⬊ᮇ㸦4㹼6 ᪥㛫㸧ࡢ 2 ࡘ࡟ศ㢮ࡉࢀࡿ㸦30㸧
ࠋ㯤యᮇࡣⓎ᝟ᚋ࡟༸ᕢෆ࡛ᡂ⇍
༸⬊ࡀ᤼༸ࡋࡓ┤ᚋ࠿ࡽጞࡲࡾ㸪㯤యࡀᡂ⇍ࡋࡓᚋ㸪㯤య㏥⾜ࡀ㛤ጞࡍࡿࡲ࡛ࡢᮇ㛫࡛
࠶ࡾ㸪㯤య㏥⾜ࡀ㛤ጞࡋ࡚࠿ࡽ᤼༸࡟⮳ࡿࡲ࡛ࡢᮇ㛫ࢆ༸⬊ᮇ࡜࠸࠺㸦30㸧
ࠋ༸⬊ᮇࡢᡂ
⇍༸⬊࠿ࡽ࢚ࢫࢺࣛࢪ࣮࢜ࣝ㸦E2㸧ࡀ⏘⏕࠾ࡼࡧศἪࡉࢀࡿ㸦30㸧ࡇ࡜࡛⾑୰ E2 ⃰ᗘࡀ
ୖ᪼ࡋ㸪ṇࡢࣇ࢕࣮ࢻࣂࢵࢡస⏝࡟ࡼࡾどᗋୗ㒊࡛ᛶ⭢่⃭࣍ࣝࣔࣥᨺฟ࣍ࣝࣔࣥ
㸦GnRH㸧ࡢࢧ࣮ࢪ≧ศἪࡀㄏ㉳ࡉࢀ㸪ࡑࢀࡀ⬻ୗᆶయ๓ⴥ࡟స⏝ࡍࡿࡇ࡜࡛㸪㯤యᙧ
ᡂ࣍ࣝࣔࣥ㸦LH㸧ࡢࢧ࣮ࢪ≧ࡢᨺฟࡀ㉳ࡇࡾ㸦80㸧
㸪ᡂ⇍༸⬊ࡢ᤼༸ࢆㄏᑟࡍࡿ㸦94㸧
ࠋ
ᡂ⇍༸⬊ࢆᵓᡂࡋ࡚࠸ࡿ㢛⢏ᒙ⣽⬊࡜ෆ༸⬊⭷⣽⬊ࡀ LH ࢧ࣮ࢪ࡟ࡼࡾ่⃭ࡉࢀ㸪ࡑࢀ
ࡒࢀ኱ᆺ㯤య⣽⬊࡜ᑠᆺ㯤య⣽⬊࡟ኚ໬ࡋ㸪ࡑࢀࡽࡀቑṪࡍࡿࡇ࡜࡛ᛴ㏿࡟㯤యࡀᙧᡂ
ࡉࢀ࡚࠸ࡃ㸦8㸧
ࠋ㯤యࡣ㸪Ⓨ᝟࿘ᮇࡢ 7 ᪥┠ࡈࢁࡲ࡛Ⓨ⫱㸪ᡂ㛗ࡋ࡚࠸ࡁ㸪ࡑࡢᚋࡣ㯤
య㏥⾜㛤ጞࡲ࡛ᶵ⬟ⓗ㯤య࡜ࡋ࡚Ꮡᅾࡍࡿࠋዷፎࡀᡂ❧ࡋ࡞࠸ሙྜ㸪Ꮚᐑ࠿ࡽࣉࣟࢫࢱ
ࢢࣛࣥࢪࣥ㸦PG㸧F2Dࡀᨺฟࡉࢀࡿ㸦54㸧ࡇ࡜࡛㯤య㏥⾜ࡀ㛤ጞࡉࢀ㸪㯤యࡣᛴ⃭࡟⦰
ᑠࡍࡿ㸦11㸪51㸪67㸧
ࠋ㯤య࠿ࡽࡣ㸪ࣉࣟࢪ࢙ࢫࢸࣟࣥ㸦P4㸧ࡀ⏘⏕㸪ศἪࡉࢀ࡚࠾ࡾ㸦68㸧
㸪
㯤యࡢⓎ⫱࡟క࠸⾑୰ P4 ⃰ᗘࡣୖ᪼ࡋ࡚࠸ࡁ㸪㯤యᙧᡂࡀ᏶஢ࡍࡿ࡜㯤య㏥⾜㛤ጞࡲ࡛
⾑୰ P4 ⃰ᗘࡣ㧗ࡃ⥔ᣢࡉࢀ㸪
㯤య㏥⾜㛤ጞ࡟క࠸ᛴ⃭࡟⾑୰ P4 ⃰ᗘࡣపୗࡋ࡚࠸ࡃ
㸦57㸧
ࠋ
ࡇࡢࡼ࠺࡞㯤యࡢⓎ⫱㸪⥔ᣢ࠾ࡼࡧ㏥⾜㸪༸⬊ࡢᡂ⇍࡜᤼༸ࡀ⧞ࡾ㏉ࡉࢀ㸪Ⓨ᝟࿘ᮇ
ࡀႠࡲࢀࡿࠋࡇࡢⓎ᝟࿘ᮇᮇ㛫୰࡟ࡣ༸ᕢෆ࡛ࡣ 2㹼3 ᅇࡢ༸⬊⩌ࡢⓎ⫱ࡀほᐹࡉࢀ㸪ࡑ
4
ࢀࡒࢀࡢ༸⬊⩌࠿ࡽ᤼༸࡟⮳ࡽ࡞࠸༸⬊ࡀ 1㹼2 ࡘⓎ⫱ࡍࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠾ࡾ㸪ࡇࡢ༸
⬊Ⓨ⫱ࡢ୍⩌ࢆ༸⬊Ἴ࡜࠸࠺㸦41㸧
ࠋ
࢘ࢩ࡟࠾࠸࡚Ⓨ᝟࿘ᮇ୰࡟Ⓨ⌧ࡍࡿ᭱ึࡢ༸⬊Ἴࡣ㸪Ⓨ᝟⤊஢ᚋࡢ༸ᕢෆ࡛ 3㹼4mm
⛬ࡢᑠ༸⬊ࡢ୍⩌㸦8㹼41 ಶ㸧ࡢⓎ⫱ࡀ㛤ጞࡉࢀ㸪ࡇࢀࢆ➨ 1 ༸⬊Ἴ࡜࠸࠺㸦41㸧
ࠋࡑࡢ
୍⩌ࡢ༸⬊ࡢ୰࡛᭱኱ࡢ༸⬊ࡀ 1 ࡘࡔࡅ㑅ᢤࡉࢀ㸪ࡑࢀ௨እࡢᑠ༸⬊ࡣ㛢㙐ࡍࡿࠋࡇࡢ
㑅ᢤࡉࢀࡓ༸⬊ࢆ୺ᖍ༸⬊࡜࠸࠸㸪
➨ 1 ༸⬊Ἴࡢ୺ᖍ༸⬊ࢆ➨ 1 ༸⬊Ἴ୺ᖍ༸⬊
㸦W1DF㸧
࡜࠸࠺ࠋW1DF ࡣⓎ᝟࿘ᮇࡢ 8㹼11 ᪥㡭ࡲ࡛Ⓨ⫱ࡍࡿࡀ㸪㯤య࠿ࡽ P4 ࡀ⏘⏕ศἪࡉࢀ࡚
࠸ࡿ᫬ᮇ࡟ᙜࡓࡿࡓࡵ㸪ᡂ⇍ࡍࡿࡇ࡜ࡀ࡛ࡁࡎ㸪ࡇࡢ W1DF ࡣ᤼༸࡟⮳ࡽࡎ㛢㙐ࡋ࡚ࡋ
ࡲ࠺㸦41㸧
ࠋࡑࢀ࡟క࠸᪂ࡓ࡞༸⬊ἼࡢⓎ⌧ࡀ㛤ጞࡉࢀ㸪ࡇࢀࢆ➨ 2 ༸⬊Ἴ࡜࠸࠺ࠋ࢘ࢩ
࡟ࡣ༸⬊Ἴࢆ 2 ࡘᣢࡘࡶࡢ࡜㸪3 ࡘᣢࡘࡶࡢࡀᏑᅾࡋ㸪ࡑࢀࡒࢀࡢⓎ⏕⋡ࡣヨ㦂࡟⏝࠸
ࡿ࢘ࢩࡢရ✀࠾ࡼࡧᖺ㱋࡟ࡼࡾ␗࡞ࡿࡇ࡜ࡀሗ࿌ࡉࢀ࡚࠸ࡿ㸦7㸪16㸪17㸪19㸪28㸪39㸪
69㸪74㸪88㸪108㸧
ࠋ༸⬊Ἴࢆ 3 ࡘᣢࡘ࢘ࢩࡢẚ⋡ࡣపᰤ㣴≧ែ㸦66㸪76㸧ࡸࣄ࣮ࢺࢫࢺ
ࣞࢫ᮲௳ୗ㸦10㸧࡛ቑຍࡍࡿ࡜࠸࠺ሗ࿌ࡀ࠶ࡿࠋW1DF ࡢ⏕Ꮡᮇ㛫ࡀ༸⬊Ἴࡢᩘ࡟ᙳ㡪
ࢆ୚࠼ࡿྍ⬟ᛶࢆ᥎ ࡋ࡚࠸ࡿሗ࿌㸦48㸧ࡶ࠶ࡿࡀ㸪ヲ⣽ࡣ᫂ࡽ࠿࡟ࡉࢀ࡚࠸࡞࠸ࠋ༸
⬊Ἴࢆ 2 ࡘᣢࡘ࢘ࢩ࡛ࡣ㸪➨ 2 ༸⬊ἼࡢⓎ⌧᪥ࡣⓎ᝟࿘ᮇࡢ 9㹼11 ᪥㡭࡛࠶ࡾ㸪༸⬊Ἴ
ࢆ 3 ࡘᣢࡘ࢘ࢩ࡛ࡣ 8㹼9 ᪥㡭࡛࠶ࡿ࡜ࡉࢀ࡚࠸ࡿ㸦4㸧
ࠋ༸⬊Ἴࢆ 3 ࡘᣢࡘ࢘ࢩ࡛ࡣ㸪➨
3 ༸⬊ἼࡢⓎ⌧᪥ࡀ 15㹼16 ᪥㡭࡛࠶ࡿ㸦4㸧
ࠋࡲࡓ㸪༸⬊Ἴࢆ 2 ࡘᣢࡘ࢘ࢩ࡜ 3 ࡘᣢࡘ࢘
ࢩ࡛㯤య㏥⾜㛤ጞ᫬ᮇ࡜Ⓨ᝟࿘ᮇ᪥ᩘࢆẚ㍑ࡋࡓ࡜ࡇࢁ㸪㯤య㏥⾜㛤ጞ᫬ᮇࡣ༸⬊Ἴࢆ
2 ࡘᣢࡘ࢘ࢩ࡛᪩ᮇ࡟㛤ጞࡉࢀ㸦2 ༸⬊Ἴ vs. 3 ༸⬊Ἴ㸻16 ᪥┠ vs. 19 ᪥┠㸧
㸪ࡑࡢ⤖ᯝ㸪
Ⓨ᝟࿘ᮇ᪥ᩘࡀ▷⦰ࡍࡿ㸦2 ༸⬊Ἴ vs. 3 ༸⬊Ἴ㸻19㹼20 ᪥┠ vs. 22㹼23 ᪥┠㸧
㸦4㸧
ࠋ༸
⬊Ἴࢆ 2 ࡘ࠶ࡿ࠸ࡣ 3 ࡘᣢࡘ࢘ࢩࡢ࡝ࡕࡽࡢሙྜ࡟࠾࠸࡚ࡶ㸪➨ 1 ༸⬊ἼࡢⓎ⌧᫬ᮇࡣ
᤼༸┤ᚋ࡛࠶ࡾ㸪㑅ᢤࡉࢀࡓ୺ᖍ༸⬊ࡣ᤼༸ࡏࡎ㸪㛢㙐ࡍࡿ࡜࠸࠺Ⅼ࡛ඹ㏻ࡋ࡚࠸ࡿࡓ
ࡵ㸪➨ 1 ༸⬊Ἴࢆ⏝࠸ࡓ༸⬊Ⓨ⫱࡟㛵ࡍࡿ◊✲ࡣከ࠸ࠋࡋ࠿ࡋ㸪ࡇࡢ➨ 1 ༸⬊Ἴࡀ࢘ࢩ
ࡢ⦾Ṫ⏕⌮࡟࠾࠸࡚ᯝࡓࡍᙺ๭ࡸព⩏࡟㛵ࡍࡿ◊✲ࡣᑡ࡞࠸ࠋ
5
㞤ࡢ⏕ṪෆศἪ⣔ࡣどᗋୗ㒊㸫ୗᆶయ㸫༸ᕢ㍈ࢆ୰ᚰ࡟ᵓᡂࡉࢀ࡚࠾ࡾ㸪どᗋୗ㒊࡛
ࡣ GnRH ࡢศἪࡀ⾜ࢃࢀ㸪ୗᆶయ๓ⴥ࡛ࡣ༸⬊่⃭࣍ࣝࣔࣥ㸦FSH㸧࡜ LH ࡀศἪࡉࢀ
ࡿ㸦80㸧
ࠋどᗋୗ㒊ࡢṇ୰㝯㉳㒊࠿ࡽᨺฟࡉࢀࡓ GnRH ࡣୗᆶయ㛛⬦࡟ධࡾ㸦65㸧
㸪ୗᆶ
య๓ⴥ࡟స⏝ࡋ㸪FSH ࠾ࡼࡧ LH ࡢྜᡂ࡜ศἪࡀಁ㐍ࡉࢀࡿࠋFSH ࡣ༸⬊ࡢⓎ⫱ࡸ༸⬊
ᩘࡢㄪ⠇࡟㛵୚ࡍࡿ࡛࣍ࣝࣔࣥ࠶ࡾ㸪༸⬊ἼⓎ⌧࡟㛵ࢃࡿ㸦6㸧
ࠋLH ࡢࣃࣝࢫ≧ศἪࡣ
GnRH ࡢᢿືᛶศἪ࡜㐃ືࡋ࡚࠾ࡾ㸦107㸧
㸪LH ࡣ୺ᖍ༸⬊ࡢ㑅ᢤ࡜୺ᖍ༸⬊ࡢⓎ⫱㸪ࡉ
ࡽ࡟ᡂ⇍࡟㛵ࢃࡿ࡛࣍ࣝࣔࣥ࠶ࡿ㸦36㸧
ࠋどᗋୗ㒊ࡢάືࡣ㸪༸ᕢ࠿ࡽศἪࡉࢀࡿᛶࢫࢸ
ࣟ࢖ࢻ࣍ࣝࣔࣥ㸦E2 ࠾ࡼࡧ P4㸧࡟ࡼࡾࣇ࢕࣮ࢻࣂࢵࢡㄪ⠇ࡉࢀ࡚࠸ࡿࠋ㐣ཤࡢሗ࿌࡟࠾
࠸࡚㸪⾑୰ P4 ⃰ᗘࡀప࠸᫬࡟ LH ࡢࣃࣝࢫ㢖ᗘࡀቑຍࡍࡿࡇ࡜㸪୍᪉࡛⾑୰ P4 ⃰ᗘࡀ㧗
࠸᫬࡟ LH ࡢࣃࣝࢫ㢖ᗘࡀῶᑡࡍࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿ㸦15㸪52㸧
ࠋLH ࡢࣃࣝࢫ≧ศἪ
ࡣ୺ᖍ༸⬊ࡢⓎ⫱࡟ᚲせ࡛࠶ࡿࡓࡵ㸪⾑୰ P4 ⃰ᗘࡀ㧗⃰ᗘ࡟࡞ࡿ㯤యᮇ࡛ࡣ㸪୺ᖍ༸⬊
ࡢⓎ⫱ࡣᢚไࡉࢀ᤼༸࡟⮳ࡿࡇ࡜ࡣ࡞ࡃ㛢㙐ࡋ࡚࠸ࡃࠋࡋ࠿ࡋ࡞ࡀࡽ㸪㯤యࡀ㏥⾜ࡋ⾑
୰ P4 ⃰ᗘࡀప࠸≧ἣ࡛ࡣ㸪LH ࣃࣝࢫ㢖ᗘࡀୖ᪼ࡍࡿࡇ࡜࡛㸪༸⬊ࡢⓎ⫱ࡀಁࡉࢀ㸪ᡂ
⇍༸⬊࡛⏘⏕ࡉࢀࡓ E2 ࡀศἪࡉࢀ㸪⾑୰ E2 ⃰ᗘࡀୖ᪼ࡍࡿࠋ⾑୰ E2 ⃰ᗘࡢୖ᪼࡟どᗋ
ୗ㒊ࡀ཯ᛂࡋ GnRH ࢧ࣮ࢪࡀᘬࡁ㉳ࡇࡉࢀ㸪ࡑࢀ࡟࿧ᛂࡋ࡚ୗᆶయ๓ⴥ࡛ࡣ LH ࢧ࣮ࢪ
ࡀㄏ㉳ࡉࢀ㸪ᡂ⇍༸⬊ࡣ᤼༸ࡍࡿ㸦81㸧
ࠋ
⫾⏕ᮇ࠾ࡼࡧ᫓ᶵⓎື๓ࡢ࢘ࢩࡢ༸ᕢ࡟࠾࠸୍࡚ḟ༸ẕ⣽⬊ࡢ࿘ᅖ࡟༸⬊ୖ⓶⣽⬊࡛
⿕ࢃࢀࡓཎጞ༸⬊ࡀᙧᡂࡉࢀࡿࠋࡑࡢᚋ㸪᫓ᶵⓎື࡟క࠸㸪ཎጞ༸⬊ࡣⓎ⫱ࢆ㛤ጞࡋ㸪
ࡇࡢⓎ⫱ࢆ㛤ጞࡋࡓ༸⬊ࡣ୍ḟ༸⬊࡜ࡼࡤࢀࡿࠋ୍ḟ༸ẕ⣽⬊ࢆྲྀࡾᅖࢇ࡛࠸ࡿ༸⬊ୖ
⓶⣽⬊ࡣయ✚ࡀቑࡋ❧᪉≧࡜࡞ࡿ㸦63㸧
ࠋࡉࡽ࡟❧᪉໬ࡋࡓୖ⓶⣽⬊ࡀቑṪ㸪㔜ᒙ໬ࡍࡿ
ࡇ࡜࡛㢛⢏ᒙ⣽⬊࡜࡞ࡾ㸪ࡉࡽ࡟ࡑࡢእഃࢆෆ༸⬊⭷⣽⬊ࡀྲྀࡾᅖࢇࡔ≧ែ࡜࡞ࡾ஧ḟ
༸⬊࡜࡞ࡿ㸦49㸧
ࠋࡇࡢẁ㝵ࡲ࡛ࡣ㸪༸⬊ࡣᛶ⭢่⃭࣍ࣝࣔࣥ㸦FSH ࠾ࡼࡧ LH㸧࡟౫Ꮡ
ࡍࡿࡇ࡜࡞ࡃⓎ⫱ࡀ㐍⾜ࡍࡿࠋ኱ᆺ༸⬊ࡢᶵ⬟ࡢᾘኻ㸪ࡘࡲࡾⓎ᝟ᚋࡢ᤼༸ࡸ➨ 1 ࠶ࡿ
࠸ࡣ➨ 2 ༸⬊Ἴ୺ᖍ༸⬊㸦W2DF㸧ࡢ㛢㙐ࡀ㉳ࡇࡿ࡜㸪୺ᖍ༸⬊ࡢ㢛⢏ᒙ⣽⬊࡛⏘⏕ࡉ
6
ࢀࡿ࢖ࣥࣄࣅࣥࡢ⾑୰⃰ᗘࡀపୗࡍࡿࠋ࢖ࣥࣄࣅࣥࡣୗᆶయ๓ⴥ࡟స⏝ࡋ FSH ࡢᨺฟࢆ
ᢚไࡍࡿࡓࡵ㸪᤼༸ᚋࡸ୺ᖍ༸⬊㛢㙐㛤ጞ࡜࡜ࡶ࡟ FSH ࡢࢧ࣮ࢪ≧ศἪࡀ㉳ࡇࡿ㸦62㸧
ࠋ
ࡑࢀࢆཷࡅ࡚஧ḟ༸⬊ࡢ୰࠿ࡽᩘ࡟ࡋ࡚ 8㹼41 ಶ㸪┤ᚄ 3㹼4mm ⛬ࡢ༸⬊ࡢⓎ⫱ࡀ㛤ጞ
ࡉࢀ㸪༸⬊ἼࡢⓎ⌧࡜࡞ࡿ㸦17㸪34㸧
ࠋ༸⬊Ἴ࡜ࡋ࡚ືဨࡉࢀࡓ༸⬊ࡣᛶ⭢่⃭࣍ࣝࣔࣥ
౫Ꮡⓗ࡟Ⓨ⫱ࢆ⥆ࡅࡿࠋࡇࡢ୍⩌ࡢ༸⬊ࡣ 1 ᪥ᙜࡓࡾ 1.5㹼2.0 mm ࡢ㏿ᗘ࡛Ⓨ⫱ࡋ࡚࠸
ࡃ㸦37㸧
ࠋ༸⬊ἼࡢⓎ⌧࠿ࡽ 2㹼3 ᪥⤒㐣ࡍࡿ࡜㸪୍⩌ࡢ୰࡛᭱኱༸⬊ࡢ㢛⢏ᒙ⣽⬊࡟࡚
ࠋE2 ࡣୗᆶయ๓ⴥ࡟స⏝ࡋ FSH
LH ཷᐜయࡀⓎ⌧ࡋ㸪E2 ⏘⏕ࡀ⾜ࢃࢀࡿࡼ࠺࡟࡞ࡿ㸦13㸧
ࡢᨺฟࢆᢚไࡍࡿ㸦38㸧
㸪ࡑࡢ⤖ᯝ㸪༸⬊Ἴࡢ༸⬊⩌ࡢ୰࡛୺ᖍ༸⬊࡜ࡋ࡚㑅ᢤࡉࢀ࡞࠿
ࡗࡓḟᖍ௨ୗࡢ FSH ౫Ꮡᛶࡢ༸⬊ࡣⓎ⫱ࡀ⥔ᣢ࡛ࡁࡎ㛢㙐ࡋ࡚࠸ࡃࠋࡋ࠿ࡋ࡞ࡀࡽ㸪᭱
኱༸⬊ࡣ㢛⢏ᒙ⣽⬊࡟ LH ཷᐜయࢆⓎ⌧ࡍࡿࡇ࡜࡛㸪ࡑࡢⓎ⫱ࢆ FSH ౫Ꮡᛶ࠿ࡽ LH ౫
Ꮡᛶ࡟ࢩࣇࢺࡍࡿࡓࡵ㸪LH ࣃࣝࢫࡢ่⃭ࢆཷࡅ࡚㸪㛢㙐ࡍࡿࡇ࡜࡞ࡃⓎ⫱ࡀ⥔ᣢࡉࢀ
ࡿࠋࡇࡢ㐣⛬ࢆ㑅ᢤ࡜࠸࠸㸪㑅ᢤࡉࢀࡓ᭱኱༸⬊ࢆ୺ᖍ༸⬊࡜࠸࠺㸦43㸧
ࠋࡇࡢ㑅ᢤ᫬࡟
࠾ࡅࡿ᭱኱༸⬊ࡢᖹᆒ┤ᚄࡣ 8.5mm ࡛࠶ࡾ㸪ḟᖍ༸⬊ࡢᖹᆒ┤ᚄࡣ 7.7mm ࡜ࡉࢀ࡚࠸
ࡿ㸦35㸧
ࠋW1DF ࡣ㸪㯤యࡀᙧᡂࡉࢀ㸪⾑୰ P4 ⃰ᗘࡀୖ᪼ࡍࡿ᫬ᮇ࡟Ⓨ⫱ࡍࡿࡓࡵ㸪࡯
࡜ࢇ࡝ࡀ᤼༸࡟⮳ࡿࡇ࡜࡞ࡃ㛢㙐ࡋ࡚ࡋࡲ࠺ࠋ୍᪉࡛㸪W2DF ࡛ࡣ㸪Ⓨ⫱ࡋ࡚࠸ࡿᮇ㛫
࡟㯤యࡢ㏥⾜ࡀ㉳ࡇࡾ⾑୰ P4 ⃰ᗘࡀపୗࡋ㸪LH ࣃࣝࢫ㢖ᗘࡀୖ᪼ࡍࡿࡇ࡜࡛୺ᖍ༸⬊
ࡢⓎ⫱ࡀ⥔ᣢࡉࢀ㸪༸⬊࠿ࡽከ㔞ࡢ E2 ࡀ⏘⏕࠾ࡼࡧศἪࡉࢀࡿࠋࡑࡢ⤖ᯝ㸪LH ࢧ࣮ࢪ
ࡀᘬࡁ㉳ࡇࡉࢀ㸪W2DF ࡣᡂ⇍ࡋ᤼༸࡟⮳ࡿࠋ
ࡇࡢ➨ 1 ༸⬊Ἴ࡟࠾࠸࡚㸪ࡑࡢⓎ⫱ືែࡸ࣍ࣝࣔࣥືែ࡟㛵ࡋ࡚ヲ⣽࡟ㄪᰝࡉࢀ࡚ࡣ
࠸ࡿࡀ㸪W1DF ⮬㌟ࡢᛶ㉁ࡸ㸪ࡑࢀࡀ⦾Ṫ⏕⌮ࡸཷ⫾ᛶ࡟ཬࡰࡍᙳ㡪࡟㛵ࡋ࡚ࡣ༑ศ࡟
᳨ウࡉࢀ࡚ࡣ࠸࡞࠸ࠋ᪤࡟㏙࡭ࡓࡼ࠺࡟㸪➨ 1 ༸⬊Ἴࡣ㯤యᙧᡂ࡜ඹ࡟Ⓨ⫱ࡍࡿࡓࡵ㸪
W1DF ࡣ⾑୰ P4 ⃰ᗘࡀప್࠿ࡽᚎࠎ࡟ୖ᪼ࡍࡿ᫬ᮇ࡟ᡂ㛗ࡍࡿࠋ୍᪉㸪➨ 2 ༸⬊Ἴࡣ㯤
యࡀ༑ศ࡟ᡂ⇍ࡋ࡚࠿ࡽⓎ⫱ࢆ㛤ጞࡍࡿࡓࡵ㸪W2DF ࡣ⾑୰ P4 ⃰ᗘࡀ㧗್࡞᫬ᮇ࡟ᡂ㛗
ࡍࡿࠋ୺ᖍ༸⬊ࡢⓎ⫱࡟ࡣ⬻ୗᆶయ๓ⴥ࠿ࡽศἪࡉࢀࡿ LH ࡢࣃࣝࢫ≧ࡢศἪࡀᚲ㡲࡛
7
࠶ࡿࡓࡵ㸪W1DF ࡜ W2DF ࡀⓎ⫱ࡍࡿᮇ㛫࡛ࡢ⾑୰ P4 ⃰ᗘ᥎⛣ࡀ␗࡞ࡿࡇ࡜࡟ࡼࡿ㸪
LH ࣃࣝࢫ㢖ᗘࡢ㐪࠸ࡀⓎ⫱ࡍࡿ୺ᖍ༸⬊ࡢᙧែࡸᶵ⬟࡟ᕪ␗ࢆࡶࡓࡽࡍ࡜⪃࠼ࡽࢀࡿࠋ
㐣ཤࡢ◊✲ࢆࡳ࡚ࡶ㸪W1DF ࡜ W2DF ࡢᛶ㉁ࡸᶵ⬟ࡢ㐪࠸ࢆ༑ศ࡟ẚ㍑ࡋࡓ◊✲ࡣ࡯࡜
ࢇ࡝⾜ࢃࢀ࡚ࡇ࡞࠿ࡗࡓࠋࡑࡇ࡛㸪W1DF ࡢ≉᭷ࡢᛶ㉁ࡸᶵ⬟ࢆ᫂ࡽ࠿࡟ࡍࡿࡓࡵ࡟㸪
W1DF ࡜ W2DF ࡢᛶ㉁ࢆẚ㍑ࡋࡓࠋ
ࡲࡓ㸪W1DF ࡢⓎ⫱ࢆไᚚࡍࡿせᅉࢆ᫂ࡽ࠿࡟ࡍࡿࡓࡵ࡟㸪➨ 1 ༸⬊ἼⓎ⫱ᮇ㛫୰࡟
࠾ࡅࡿᛶࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥືែࡸ㸪༸ᕢෆ࡛Ⓨ⫱ࡍࡿ㯤య࡜ࡢ఩⨨㛵ಀ࡞࡝ࡢせᅉ࡜
W1DF ࡢᛶ㉁ࢆẚ㍑ࡍࡿࡇ࡜࡟ࡋࡓࠋࡉࡽ࡟㸪㐣ཤࡢሗ࿌࠿ࡽ㯤యࡀᏑᅾࡍࡿ༸ᕢ࡜ྠ
ഃࡢᏊᐑゅࡢෆ⭷୰ࡢ P4 ⃰ᗘࡀ㧗࠸ࡇ࡜㸦20㸧
㸪᤼༸๓༸⬊ࡀᏑᅾࡍࡿ༸ᕢ࡜ྠഃࡢ༸
⟶୰ࡢ E2 ⃰ᗘࡀ㧗࠸ࡇ࡜㸦99㸧ࡀ▱ࡽࢀ࡚࠾ࡾ㸪ᒁᡤ࡛ࡢ༸ᕢ࡜Ꮚᐑゅࡢᐦ᥋࡞㛵㐃ᛶ
ࡀᏑᅾࡍࡿࡇ࡜ࡀ♧၀ࡉࢀࡿࠋࡋ࠿ࡋ࡞ࡀࡽ㸪W1DF ࡀྠ୍༸ᕢෆࡢ㯤యࡸᏊᐑゅ࡟ᑐ
ࡋ࡚ᒁᡤⓗ࡟࡝ࡢࡼ࠺࡞ᙳ㡪ࢆ୚࠼ࡿࡢ࠿ࢆㄪᰝࡋࡓ◊✲ࡣぢᙜࡓࡽ࡞࠸ࠋ
ᮏ◊✲࡟࠾࠸࡚㸪➨ 2 ❶࡛ࡣ㸪W1DF ࡢᛶ㉁࠾ࡼࡧᶵ⬟ࢆ᫂ࡽ࠿࡟ࡍࡿࡓࡵ㸪㠀Ἢங
∵ࢆ⏝࠸࡚㸪༸⬊ࡢⓎ⫱ືែ࡜㯤య㏥⾜ㄏ㉳ᚋࡢ༸⬊ࡢᡂ⇍࠾ࡼࡧ᤼༸࡟⮳ࡿ㐣⛬ࡢ༸
⬊ቨ⾑ὶ㸪ࢫࢸࣟ࢖ࢻ⃰ᗘ࠾ࡼࡧ㢛⢏ᒙ⣽⬊࡛Ⓨ⌧ࡋ࡚࠸ࡿᅉᏊ㸪ࡉࡽ࡟ࡣ᤼༸ᚋ࡟ᙧ
ᡂࡉࢀࡿ㯤యⓎ⫱ࢆ W2DF ࡜ẚ㍑ࡋࡓࠋ
➨ 3 ❶࡛ࡣ㸪W1DF ࡢⓎ⫱ࢆไᚚࡍࡿせᅉࢆ᫂ࡽ࠿࡟ࡍࡿࡓࡵ㸪W1DF ࡢⓎ⫱ࡀ㸪Ⓨ
⫱ᮇ㛫୰ࡢ⾑୰ P4 ⃰ᗘ࠾ࡼࡧྠ୍༸ᕢෆ࡛ࡢ㯤యࡢ᭷↓࡟ࡼࡿ༸ᕢᒁᡤෆ࡛ࡢᙳ㡪ࢆ
ཷࡅࡿࡢ࠿ࢆㄪ࡭ࡓࠋ
➨ 4 ❶࡛ࡣ㸪Ἢங∵ࢆ⏝࠸㸪W1DF ࡀ⦾Ṫ⏕⌮࡟࡝ࡢࡼ࠺࡞ᙳ㡪ࢆ୚࠼ࡿ࠿ࢆ┠ⓗ࡟㸪
୺ᖍ༸⬊ࡀ㯤య࡜ྠഃࡢ༸ᕢ࡟Ꮡᅾࡍࡿሙྜ࡜཯ᑐഃ࡟Ꮡᅾࡍࡿሙྜࡢཷ⫾ᛶࢆẚ㍑ࡋ
ࡓࠋ
8
➨㸰❶
➨ 1 ༸⬊Ἴ୺ᖍ༸⬊㸦W1DF㸧ࡢⓎ⫱ືែ㸪᤼༸๓ᚋࡢ
ᶵ⬟࠾ࡼࡧ᤼༸ᚋ࡟ᙧᡂࡉࢀࡿ㯤యࡢᛶ㉁
9
2㸫1㸬ᗎㄽ
࢘ࢩࡢ➨ 1 ༸⬊ἼࡣⓎ᝟࣭᤼༸⤊஢┤ᚋ࠿ࡽ༸ᕢෆ࡛Ⓨ⌧ࡍࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠾ࡾ㸪
㏻ᖖࡣ㸪㯤యࡀᏑᅾࡍࡿ᮲௳ୗ࡛Ⓨ⫱ࡍࡿࡓࡵ㸪W1DF ࡣⓎ᝟࿘ᮇࡢ 8㹼10 ᪥ࡲ࡛࡟㛢
㙐ࡋ㸪᤼༸࡟⮳ࡿࡇ࡜ࡣ࡞࠸㸦41㸧
ࠋ࢘ࢩࡢ༸⬊ࡢⓎ⫱ືែ㸪Ⓨ⫱࠾ࡼࡧ㑅ᢤ࡟㛵ࢃࡿෆ
ศἪ࣍ࣝࣔࣥືែࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࢆ┠ⓗ࡟㸪ࡇࢀࡲ࡛ W1DF ࡟ὀ┠ࡋ࡚ヲ⣽࡟◊✲
ࡀ⾜ࢃࢀ࡚ࡁࡓ㸦9㸪53㸪93㸪103㸧ࡀ㸪W1DF ⮬㌟ࡢᛶ㉁㸪ᶵ⬟࠾ࡼࡧ᤼༸ㄏ㉳᫬ࡢ≉
ᚩ࡟ࡘ࠸࡚ࡣ༑ศ࡟᳨ウࡉࢀ࡚ࡇ࡞࠿ࡗࡓࠋ➨ 2 ༸⬊ἼࡣⓎ᝟࿘ᮇࡢ 9㹼10 ᪥࡟Ⓨ⌧࣭
Ⓨ⫱ࡋ㸪㯤యࡢ㏥⾜࡟క࠸୺ᖍ༸⬊ࡣᡂ⇍㸪Ⓨ᝟ࢆㄏ㉳ࡋ᤼༸࡟⮳ࡿ㸦88㸧
ࠋ➨ 1 ༸⬊Ἴ
ࡣ㯤యᙧᡂ࡜ඹ࡟Ⓨ⫱ࡍࡿࡓࡵ㸪W1DF ࡣ P4 ⃰ᗘࡀప್࠿ࡽᚎࠎ࡟ୖ᪼ࡍࡿ᫬ᮇ࡟ᡂ㛗
ࡍࡿࠋ୍᪉㸪➨ 2 ༸⬊Ἴࡣ㯤యࡀ༑ศ࡟ᡂ⇍ࡋ࡚࠿ࡽⓎ⫱ࢆ㛤ጞࡍࡿࡓࡵ㸪W2DF ࡣ⾑
୰ P4 ⃰ᗘࡀ㧗್࡞᫬ᮇ࡟ᡂ㛗ࡍࡿࠋࡘࡲࡾ㸪୧⪅ࡣ⾑୰ P4 ⃰ᗘ᥎⛣ࡀ␗࡞ࡿ≧ἣୗ࡛
Ⓨ⫱ࡍࡿࡓࡵ㸪ࡑࢀࡒࢀࡢ୺ᖍ༸⬊ࡢⓎ⫱ືែ㸪ࢫࢸࣟ࢖ࢻ⏘⏕⬟㸪᤼༸࡟క࠺ኚ໬࠾
ࡼࡧ᤼༸ᚋ࡟ᙧᡂࡉࢀࡿ㯤యࡢᙧែࡸᶵ⬟ࡀ␗࡞ࡿྍ⬟ᛶࡀ࠶ࡿࠋ
ࡑࡇ࡛㸪ᮏ❶࡛ࡣ㸪W1DF ࡢᛶ㉁࠾ࡼࡧᶵ⬟ࢆ᫂ࡽ࠿࡟ࡍࡿࡓࡵ㸪㠀Ἢங∵ࢆ⏝࠸࡚㸪
༸⬊ࡢⓎ⫱ືែ࡜㯤య㏥⾜ㄏ㉳ᚋࡢᡂ⇍㸪᤼༸࡟⮳ࡿ㐣⛬ࡢ༸⬊ቨ⾑ὶ㸪ࢫࢸࣟ࢖ࢻ⃰
ᗘ࠾ࡼࡧ㢛⢏ᒙ⣽⬊࡛Ⓨ⌧ࡋ࡚࠸ࡿᅉᏊࡉࡽ࡟ࡣ᤼༸ᚋ࡟ᙧᡂࡉࢀࡿ㯤యⓎ⫱ࢆ W2DF
࡜ẚ㍑ࡋㄪ࡭ࡓࠋ
2㸫2㸬ヨ㦂 1㸸༸⬊ἼⓎ⌧࠿ࡽ 7 ᪥┠ࡲ࡛ࡢ W1DF ࡜ W2DF ࡢⓎ⫱ືែ࠾ࡼࡧ
༸⬊ቨ⾑ὶࡢẚ㍑
2㸫2㸫1㸬౪ヨື≀
10
⮫ᗋⓗ࡟೺ᗣ࡛㸪ṇᖖ࡞Ⓨ᝟࿘ᮇࢆ᭷ࡍࡿ࣍ࣝࢫࢱ࢖ࣥ✀㠀Ἢங∵ 8 㢌㸦ᖹᆒᖺ㱋㸸
5.0 r 1.8 ṓ㸪ᖹᆒsᶆ‽ㄗᕪ㸧ࢆ⏝࠸ࡓࠋ ᑐ㇟∵ࡣᖏᗈ␆⏘኱Ꮫ␆⏘ࣇ࢕࣮ࣝࢻ⛉Ꮫࢭ
ࣥࢱ࣮ෆࡢࣃࢻࢵࢡ࡟࡚㸪ࢥ࣮ࣥࢧ࢖࣮ࣞࢪ㸪஝ⲡ࠾ࡼࡧ⃰ཌ㣫ᩱࡀΰྜࡉࢀࡓ TMR
ࡀ⤥୚ࡉࢀ㸪⮬⏤㣧Ỉ࡛ࡁࡿ≧ἣ࡛㣫㣴ࡉࢀ࡚࠸ࡓࠋᐇ㦂ෆᐜࡣᖏᗈ␆⏘኱Ꮫࡢᐇ㦂೔
⌮ጤဨ఍࡟࡚ᢎㄆࡉࢀ࡚࠸ࡿࠋ
2㸫2㸫2㸬ᐇ㦂᪉ἲ
8 㢌ࡢ࢘ࢩࡣ➨ 1 ༸⬊Ἴヨ㦂⩌㸦n㸻4㸧࡜➨ 2 ༸⬊Ἴヨ㦂⩌㸦n㸻4㸧࡟ศࡅࡓࠋࡑࢀ
ࡒࢀࡢ⩌ࡣヨ㦂⤊஢ 2 ࠿᭶ᚋ࡟㸪ࣛࢸࣥ᱁Ꮚἲࢆ⏝࠸࡚ࢡࣟࢫ࣮࢜ࣂ࣮ヨ㦂ࢆ⾜ࡗࡓࠋ
ࡑࡢࡓࡵ㸪ࡑࢀࡒࢀࡢ⩌࡟ࡣ 8 㢌ࡢ࢘ࢩࡀ඲࡚ྵࡲࢀ࡚࠸ࡿ㸦n㸻8㸧
ࠋ
➨ 1 ༸⬊Ἴヨ㦂⩌࡛ࡣ㸪⮬↛Ⓨ᝟㛤ጞᚋ 12 ᫬㛫ࡈ࡜࡟㉸㡢Ἴ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚༸
ᕢࢆほᐹࡋࡓࠋ᤼༸๓༸⬊ࡢᾘኻࢆ☜ㄆࡋࡓ᫬Ⅼࢆ Day 0 ࡜ࡋࡓࠋ༸⬊㑅ᢤࡀ⤊஢ࡋࡓ
࡜⪃࠼ࡽࢀࡿ Day 3 ࠿ࡽ 5 ࡲ࡛ࡢᮇ㛫㸪㉸㡢Ἴ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚୺ᖍ༸⬊ࡢほᐹࢆ
⾜ࡗࡓࠋࡲࡓ Day 6 ࡟ࡣ࣮࢝ࣛࢻࣉࣛ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚୺ᖍ༸⬊ࡢᖹᆒ┤ᚄ࠾ࡼࡧ
༸⬊ቨ⾑ὶࢆ ᐃࡋࡓࠋࡲࡓ Day 0㹼6 ࡢ㛫㸪1 ᪥࡟ 1 ᅇṇ୰ᑿ㟼⬦ࡼࡾ᥇⾑ࢆ⾜ࡗࡓࠋ
➨ 2 ༸⬊Ἴ⩌࡛ࡣ㸪⮬↛Ⓨ᝟⤊஢ᚋࡢ᤼༸☜ㄆ᪥ࢆ Day 㸫7 ࡜ࡋࡓࠋ➨ 2 ༸⬊ἼⓎ⌧
ࢆㄏ㉳ࡍࡿࡓࡵ࡟㸪Day 㸫2 ࡟ W1DF ࡢ᤼༸ㄏ㉳ࢆ┠ⓗ࡟ GnRH㸦100 μg 㓑㓟ࣇ࢙ࣝࢳ
ࣞࣜࣥ㸪➽⫗ෆᢞ୚ 㸹 ࢥࣥࢭ࣮ࣛࣝ㸹 ࢖ࣥࢱ࣮࣋ࢵࢺᰴᘧ఍♫㸪኱㜰㸪᪥ᮏ㸧ࢆᢞ୚
ࡋࡓࠋGnRH ᢞ୚ 36 ᫬㛫ᚋ࡟㉸㡢Ἴ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚ W1DF ࡀ᤼༸ࡋ࡚࠸ࡿࡇ࡜
ࢆ☜ㄆࡋ㸪ࡑࡢ᫬Ⅼࢆ Day 0 ࡜ࡋࡓࠋࡑࡢᚋ㸪➨ 1 ༸⬊Ἴ⩌࡜ྠᵝ࡟༸⬊㑅ᢤࡀ⤊஢ࡋ
ࡓ࡜⪃࠼ࡽࢀࡿ Day 3 ࠿ࡽ 5 ࡲ࡛ࡢᮇ㛫㸪㉸㡢Ἴ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚୺ᖍ༸⬊ࡢᖹᆒ
┤ᚄࢆ ᐃࡋࡓࠋࡲࡓ Day 6 ࡟ࡣ࣮࢝ࣛࢻࣉࣛ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚୺ᖍ༸⬊ࡢᖹᆒ┤
11
ᚄ࠾ࡼࡧ༸⬊ቨ⾑ὶࡢ ᐃࢆ⾜ࡗࡓࠋࡲࡓ Day 0㹼6 ࡢ㛫㸪1 ᪥࡟ 1 ᅇṇ୰ᑿ㟼⬦ࡼࡾ᥇
⾑ࢆ⾜ࡗࡓࠋヨ㦂 1 ࡢࣉࣟࢺࢥ࣮ࣝࡢᶍᘧᅗࢆ Fig. 2.1.࡟♧ࡋࡓࠋ
2㸫2㸫3㸬༸⬊ᙧែࡢほᐹ
Day 3࠿ࡽ5ࡲ࡛ࡢ୺ᖍ༸⬊ࡢᖹᆒ┤ᚄࡣ㸪5.0MHzࡢࣜࢽ࢔ࣉ࣮ࣟࣈࡀ௜ᒓࡋࡓ⤒┤⭠㉸
㡢Ἴ⏬ീデ᩿⿦⨨㸦HS̺101V㸪ᮏከ㟁Ꮚ㸪ឡ▱㸪᪥ᮏ㸧ࢆ⏝࠸࡚ ᐃࡋࡓࠋࣉ࣮ࣟࣈࢆ
ᡭᣦ࡜࡜ࡶ࡟┤⭠ෆ࡟ᤄධࡋ㸪ᕥྑ୧ഃ༸ᕢࡢ᩿ᒙീࢆほᐹࡋࡓࠋ୺ᖍ༸⬊ࡢ༸⬊᩿ᒙ⏬
ീࡀ᭱኱࡟࡞ࡿࡼ࠺㟼Ṇ⏬ࢆグ㘓ࡋ㸪ࣃࢯࢥࣥୖ࡟㟼Ṇ⏬ࢆ⛣ືࡉࡏ㸪୺ᖍ༸⬊ࡣ㛗ᚄ࡜
▷ᚄࡢᖹᆒ್ࢆᖹᆒ┤ᚄ࡜ࡋ㸪ࢹ࣮ࢱ࡜ࡋ࡚⏝࠸ࡓࠋ
Day 6࡟࠾ࡅࡿ୺ᖍ༸⬊ࡢ┤ᚄ࠾ࡼࡧ༸⬊ቨ⾑ὶࡣ㸪8.0MHzࡢࣜࢽ࢔ࣉ࣮ࣟࣈ㸦1739̺
RSࣉ࣮ࣟࣈ㸹GEᶓἙ࣓ࢹ࢕࢝ࣝࢩࢫࢸ࣒㸪ᮾி㸪᪥ᮏ㸧ࢆ᥋⥆ࡋࡓ࣮࢝ࣛࢻࣉࣛ㉸㡢Ἴ
⏬ീデ᩿⿦⨨㸦LOGIQ Book XP㸪GE࣓ࢹ࢕࢝ࣝࢩࢫࢸ࣒㸪ᮾி㸪᪥ᮏ㸧ࢆ⏝࠸࡚࣮࢝ࣛ
࣮ࣔࢻ࡟ࡼࡾほᐹࢆ⾜ࡗࡓࠋ༸⬊ቨ⾑ὶࡢ᳨ᰝ᪉ἲࡣࣉ࣮ࣟࣈࢆᡭᣦ࡜࡜ࡶ࡟┤⭠ෆ࡟ᤄ
ධࡋ㸪୺ᖍ༸⬊ࡢ᩿ᒙീࢆほᐹࡋࡓࠋ༸⬊┤ᚄࡀ᭱኱࡛࠿ࡘ⾑ὶ㠃✚ࡀ᭱኱࡟࡞ࡿࡼ࠺࡞
㟼Ṇ⏬ࢆグ㘓ࡋ㸪ᖹᆒ┤ᚄ㸪༸⬊ቨ⾑ὶ㠃✚㸦BFA㸧࠾ࡼࡧ⾑ὶศᕸ๭ྜ㸦BF%㸧ࢆ⟬ฟ
ࡋࡓࠋ
BFAࡢ⟬ฟࡣ㸪グ㘓ࡋࡓ᧜ᙳ⏬ീࢆࣃࢯࢥࣥෆ࡟ྲྀࡾ㎸ࡳ㸪Photoshop 5.5㸦Adobe Systems
Inc.㸪San Jose㸪CA㸪USA㸧ࢆ⏝࠸࡚⾑ὶ㡿ᇦࢆⓑ㯮⏬ീ࡟ኚ᥮ࡋ㸪Pop Imaging㸦ࢹࢪࢱ
࣭ࣝࣅ࣮࢖ࣥࢢ࣭࢟ࢵࢬ㸪⚄ዉᕝ㸪᪥ᮏ㸧ࢆ⏝࠸࡚⾑ὶ㠃✚ࢆ⟬ฟࡋ㸪BFA࡜ࡋ࡚ࢹ࣮ࢱ
ࢆ⏝࠸ࡓ㸦Fig. 2.2.㸧ࠋ
BF㸣ࡣ㸪᧜ᙳࡋࡓ⏬ീࢆ⏝࠸࡚㸪༸⬊෇࿘࡟ᑐࡍࡿ⾑ὶศᕸࡢ๭ྜࢆホ౯ࡍࡿࡶࡢ࡛࠶
ࡾ㸪༸⬊ቨෆ࡛ࡢ⾑⟶ศᕸࡢ⛬ᗘࢆ♧ࡍᣦᶆ࡜ࡋ࡚⏝࠸ࡓࠋPhotoshop 5.5ࢆ⏝࠸࡚༸⬊෇
12
࿘࡜⾑ὶศᕸࡀࡳࡽࢀࡿ༸⬊ቨࡢ㛗ࡉࢆ⟬ฟࡋ㸪⾑ὶศᕸࡀࡳࡽࢀࡿ༸⬊ቨࡢ㛗ࡉࢆ༸⬊
෇࿘࡛㝖ࡋࡓࡶࡢࢆBF㸣࡜ࡋ࡚ࢹ࣮ࢱࢆ⏝࠸ࡓࠋ
2㸫2㸫4㸬᥇⾑
ヨ㦂ᮇ㛫୰ࡢDay 0࠿ࡽ6࡟21G᥇⾑㔪࡜࣊ࣃࣜࣥຍ┿✵᥇⾑⟶㸦࣋ࣀࢪ࢙ࢡࢺϩ┿✵᥇
⾑⟶㸪TERUMO㸪ᮾி㸧ࢆ⏝࠸࡚ᑿ㟼⬦ࡼࡾ10mlࡢ᥇⾑ࢆ⾜ࡗࡓࠋ᥇ྲྀࡋࡓ⾑ᾮࡣịỈ
୰࡟࡚ᛴ෭ᚋ㸪4Υ࡛2,000 g㸪20ศ㛫㐲ᚰࡋ㸪⾑₢ศ㞳ᚋ㸪⾑୰P4⃰ᗘ ᐃࡲ࡛㸫30Υ࡟
࡚෾⤖ಖᏑࡋࡓࠋ
2㸫2㸫5㸬⾑୰P4⃰ᗘࡢ ᐃ
⾑୰P4⃰ᗘࡢ ᐃࡣ2ᢠయἲ࡟ࡼࡿ㓝⣲ච␿ ᐃἲ㸦EIA㸧࡟ࡼࡾ ᐃࡋࡓࠋEIAࡢᡭ㡰
ࡣ௨๓ࡢሗ࿌࡟ᇶ࡙࠸࡚⾜ࡗࡓ㸦64㸧ࠋ⾑₢ࡼࡾP4ࢆᢳฟࡍࡿࡓࡵ࡟㸪⾑₢200μl࡟ࢪ࢚ࢳ
࢚࣮ࣝࢸࣝ㸦㛵ᮾ໬Ꮫ㸪ᮾி㸪᪥ᮏ㸧1.0mlࢆຍ࠼㸪ᨩᢾᶵ㸦Mix-EVR㸪ࢱ࢖ࢸࢵࢡ㸪ᇸ
⋢㸪᪥ᮏ㸧ࢆ⏝࠸࡚30ศ㛫࣎ࣝࢸࢡࢫࡋ㸪ࡑࡢᚋᐊ ࡟࡚40ศ㛫㟼⨨ࡋࡓࠋࡑࡢᚋ㸪㸫30Υ
ࡢ෭෾ᗜ࡟⛣ືࡋ㸪24᫬㛫࠿ࡅ࡚᏶඲࡟෾⤖ࡉࡏࡓࠋ෾⤖ᚋ㸪ᾮ┦㒊ศࢆ5mlヨ㦂⟶࡟ࢹ
࢝ࣥࢺࡋ㸪ࢻࣛࣇࢺෆࡢ࢛࣮࢘ࢱ࣮࣭ࣂࢫ࡟ᾐࡋ㸪40Υࡲ࡛ୖ᪼ࡉࡏ࡞ࡀࡽࢪ࢚ࢳ࢚࣮ࣝ
ࢸࣝࢆ᥹Ⓨࡉࡏࡓᚋ㸪50Υࡲ࡛ୖ᪼ࡉࡏ↓⮯࡟࡞ࡿࡲ࡛᏶඲࡟᥹Ⓨࡉࡏࡓࠋ᥹Ⓨᚋ㸪ヨ㦂
⟶࡟࢔ࢵࢭ࢖࣭ࣂࢵࣇ࢓࣮㸦7.12g㸹NA2HPO4㸪8.5g㸹NaCl㸪1.0g㸹BSA㸪pH 7.2㸹1N-HCL
࡛ㄪᩚ㸧ࢆ200μlຍ࠼㸪20ศ㛫࣎ࣝࢸࢡࢫࡋࡓࠋࡇࡢ ᐃἲ࡟ࡼࡿP4ࡢᢳฟຠ⋡84㸣࡛࠶ࡗ
ࡓࠋEIAࡣᢠ࢘ࢧࢠIgGᢠయ㸦12.5μg/ml㸹⏕໬Ꮫᕤᴗᰴᘧ఍♫㸪ᮾி㸪᪥ᮏ㸧࡛⿕ࢃࢀࡓ
96✰ELISAࣉ࣮ࣞࢺ㸦Corning Glass Works㸪Corning㸪New York㸪USA㸧 ࢆ⏝࠸࡚⾜ࡗࡓࠋ
⃰ᗘ ᐃࡣ㸪
ࢫࢱࣥࢲ࣮ࢻ࠾ࡼࡧࢧࣥࣉࣝ15μl࡜100μlࡢP4࣏ࣜࢡ࣮ࣟࢼࣝᢠయ⁐ᾮ
㸦OK-1㸧
㸦1㸸300,000㸧࡜100μlࡢhorseradish peroxidase 㸦1㸸50,000㸧ࢆΰ࿴ࡋ㸪4Υ࡟࡚20᫬㛫௨
13
ୖ᣺┞ࡉࡏࡓࠋP4ࡢᶆ‽᭤⥺ࡣ0.05㹼50ng/mlࡢ⠊ᅖ࡛㸪 ᐃෆኚື࠾ࡼࡧ ᐃ㛫ኚືࡣࡑ
ࢀࡒࢀ5.2㸣࠾ࡼࡧ7.4%࡛࠶ࡗࡓࠋ
2㸫2㸫6㸬⤫ィฎ⌮
⤖ᯝࡣࡍ࡭࡚ᖹᆒ್sᶆ‽ㄗᕪ࡛♧ࡋࡓࠋ⾑୰ P4 ⃰ᗘ᥎⛣ࡢᕪࡢ᳨ᐃࢆ⾜࠺࡟ᙜࡓࡗ
࡚㸪2 ඖ㓄⨨ศᩓศᯒࢆ⾜࠸㸪඲యࡢኚ໬ࡢ᭷ពᛶࢆㄪ࡭㸪஺஫స⏝ࡀ᭷ព࡛࠶ࡗࡓሙ
ྜ㸪Bartlet ᳨ᐃࢆ⾜࠸ศᩓࡢᆒ୍ᛶࢆ᳨ᐃࡋࡓᚋ㸪Post-hoc ᳨ᐃ࡜ࡋ࡚ Schefe ࡢከ⩌ẚ
㍑᳨ᐃࢆ⏝࠸ࡓࠋDay 6 ࡟࠾ࡅࡿ༸⬊ቨ⾑ὶࡢẚ㍑࡟ࡣ㸪F ᳨ᐃࢆ⾜࠸ศᩓࡢᆒ୍ᛶࢆ☜
ㄆࡋࡓᚋ㸪Student ࡢ t ᳨ᐃࢆ⏝࠸ࡓࠋ༴㝤⋡ 10㸣ᮍ‶㸦P < 0.1㸧ࢆഴྥ࠶ࡾ࡜ࡋࠊ༴㝤
⋡ 5㸣ᮍ‶㸦P < 0.05㸧࡛᭷ពᕪ࠶ࡾ࡜ࡋࡓࠋ⤫ィฎ⌮࡟ࡣ⤫ィฎ⌮ࢯࣇࢺ࡛࠶ࡿ StatView
㸦Abacus Concepts㸪Inc.㸪Berkeley㸪CA㸪USA㸧ࢆ⏝࠸ࡓࠋ
2㸫3㸬ヨ㦂 2㸸Ⓨ᝟࠾ࡼࡧ᤼༸ㄏ㉳᫬࡟࠾ࡅࡿ W1DF ࡜ W2DF ࡢⓎ⫱ືែ㸪༸⬊ቨ⾑ὶ
࠾ࡼࡧ⾑୰ E2 ⃰ᗘࡢẚ㍑
2㸫3㸫1㸬౪ヨື≀
2㸫2㸬❶࡜ྠᵝࡢື≀ࢆ౪ヨࡋࡓࠋ
2㸫3㸫2㸬ᐇ㦂᪉ἲ
ヨ㦂 1 ࡜ྠࡌࣉࣟࢺࢥ࣮࡛ࣝ➨ 1 ༸⬊Ἴヨ㦂⩌࡜➨ 2 ༸⬊Ἴヨ㦂⩌ࢆ‽ഛࡋࡓࠋ
ࡑࡢᚋ㸪Ⓨ᝟࠾ࡼࡧ᤼༸ㄏ㉳ࢆ⾜࠺ࡇ࡜ࢆ┠ⓗ࡟㸪Day 6 ࡟ PGF2α 㸦25 mg ࢺ࣓ࣟࢱ
࣑ࣥࢪࣀࣉࣟࢫࢺ㸪➽⫗ෆᢞ୚㸪ࣉࣟࢼࣝࢦࣥ F㸪ࢰ࢚ࢸ࢕ࢫ㸪ᮾி㸪᪥ᮏ㸧ࢆᢞ୚ࡋ
㯤య㏥⾜ࢆㄏ㉳ࡋ㸪48 ᫬㛫ᚋࡢ Day 8 ࡟ GnRH ࢆᢞ୚ࡋ᤼༸ㄏ㉳ࢆ⾜ࡗࡓࠋDay 6㸪8
14
࠾ࡼࡧ 9 ࡟࣮࢝ࣛࢻࣉࣛ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚୺ᖍ༸⬊ࡢᖹᆒ┤ᚄ࠾ࡼࡧ༸⬊ቨ⾑ὶࡢ
ᐃࢆ⾜ࡗࡓࠋࡲࡓ Day 6㹼9 ࡢ㛫㸪1 ᪥࡟ 1 ᅇṇ୰ᑿ㟼⬦ࡼࡾ᥇⾑ࢆ⾜ࡗࡓࠋヨ㦂 2 ࡢ
ࣉࣟࢺࢥ࣮ࣝࡢᶍᘧᅗࢆ Fig. 2.5.࡟♧ࡋࡓࠋ
2㸫3㸫3㸬 ༸⬊ᙧែࡢほᐹ
Day 6㸪8࠾ࡼࡧ9࡟࠾ࡅࡿ୺ᖍ༸⬊ࡢ┤ᚄ࠾ࡼࡧ༸⬊ቨ⾑ὶࡣ㸪8.0MHzࡢࣜࢽ࢔ࣉ࣮ࣟ
ࣈ㸦1739̺RSࣉ࣮ࣟࣈ㸹GEᶓἙ࣓ࢹ࢕࢝ࣝࢩࢫࢸ࣒㸪ᮾி㸪᪥ᮏ㸧ࢆ᥋⥆ࡋࡓ࣮࢝ࣛࢻ
ࣉࣛ㉸㡢Ἴ⏬ീデ᩿⿦⨨㸦LOGIQ Book XP㸪GE࣓ࢹ࢕࢝ࣝࢩࢫࢸ࣒㸪ᮾி㸪᪥ᮏ㸧ࢆ⏝
࠸࡚࣮࣮࢝ࣛࣔࢻ࡟ࡼࡾほᐹࢆ⾜ࡗࡓࠋ༸⬊ቨ⾑ὶࡢ᳨ᰝ᪉ἲࡣࣉ࣮ࣟࣈࢆᡭᣦ࡜࡜ࡶ࡟
┤⭠ෆ࡟ᤄධࡋ㸪୺ᖍ༸⬊ࡢ᩿ᒙീࢆほᐹࡋࡓࠋ༸⬊┤ᚄࡀ᭱኱࡛࠿ࡘ⾑ὶ㠃✚ࡀ᭱኱࡟
࡞ࡿࡼ࠺࡞㟼Ṇ⏬ࢆグ㘓ࡋ㸪ヨ㦂1࡜ྠᵝࡢ᪉ἲ࡛ᖹᆒ┤ᚄ㸪BFA࠾ࡼࡧBF%ࢆ⟬ฟࡋࡓࠋ
2㸫3㸫4㸬᥇⾑
ヨ㦂ᮇ㛫୰ࡢDay 6㹼9࡟21G᥇⾑㔪࡜࣊ࣃࣜࣥຍ┿✵᥇⾑⟶㸦࣋ࣀࢪ࢙ࢡࢺϩ┿✵᥇⾑
⟶㸪TERUMO㸪ᮾி㸪᪥ᮏ㸧ࢆ⏝࠸࡚ᑿ㟼⬦ࡼࡾ10mlࡢ᥇⾑ࢆ⾜ࡗࡓࠋ᥇ྲྀࡋࡓ⾑ᾮࡣ
ịỈ୰࡟࡚ᛴ෭ᚋ㸪4Υ࡛2,000 g㸪20ศ㛫㐲ᚰࡋ㸪⾑₢ศ㞳ᚋ㸪⾑୰P4⃰ᗘ࠾ࡼࡧ⾑୰E2
⃰ᗘ ᐃࡲ࡛㸫30Υ࡟࡚෾⤖ಖᏑࡋࡓࠋ
2㸫3㸫5㸬⾑୰P4࠾ࡼࡧE2⃰ᗘࡢ ᐃ
⾑୰P4⃰ᗘࡣヨ㦂1࡜ྠᵝࡢᡭἲ࡛EIA࡟ࡼࡾ ᐃࡋࡓࠋࡇࡢ ᐃἲ࡟ࡼࡿP4ࡢᢳฟຠ⋡
ࡣ80㸣࡛࠶ࡗࡓࠋ ᐃෆኚື࠾ࡼࡧ ᐃ㛫ኚືࡣࡑࢀࡒࢀ4.7㸣࠾ࡼࡧ6.5㸣࡛࠶ࡗࡓࠋ⾑
୰E2⃰ᗘࡣDay 8ࡢࡳ ᐃࢆ⾜ࡗࡓࠋ⾑₢ࡼࡾE2ࢆᢳฟࡍࡿࡓࡵ࡟㸪⾑₢2.0ml࡟ࢪ࢚ࢳࣝ
࢚࣮ࢸࣝ㸦㛵ᮾ໬Ꮫ㸪ᮾி㸪᪥ᮏ㸧6.0mlࢆຍ࠼㸪ᨩᢾᶵ㸦DM-301㸪࢔ࢬ࣡ࣥ㸪኱㜰㸪᪥
15
ᮏ㸧ࢆ⏝࠸࡚60ศ㛫࣎ࣝࢸࢡࢫࡋ㸪ࡑࡢᚋᐊ ࡟࡚60ศ㛫㟼⨨ࡋࡓࠋࡑࡢᚋ㸫30Υࡢ෭෾
ᗜ࡟⛣ືࡋ㸪24᫬㛫࠿ࡅ࡚᏶඲࡟෾⤖ࡉࡏࡓࠋ෾⤖ᚋ㸪ᾮ┦㒊ศࢆ10mlヨ㦂⟶࡟ࢹ࢝ࣥࢺ
ࡋ㸪ࢻࣛࣇࢺෆࡢ࢛࣮࢘ࢱ࣮࣭ࣂࢫ࡟ᾐࡋ㸪40Υࡲ࡛ୖ᪼ࡉࡏ࡞ࡀࡽࢪ࢚ࢳ࢚࣮ࣝࢸࣝࢆ
᥹Ⓨࡉࡏࡓᚋ㸪50Υࡲ࡛ୖ᪼ࡉࡏ↓⮯࡟࡞ࡿࡲ࡛᏶඲࡟᥹Ⓨࡉࡏࡓࠋ᥹Ⓨᚋ㸪ヨ㦂⟶࡟࢔
ࢵࢭ࢖࣭ࣂࢵࣇ࢓࣮ࢆ200μlຍ࠼㸪20ศ㛫࣎ࣝࢸࢡࢫࡋࡓࠋࡇࡢᡭἲ࡟ࡼࡾ⾑₢୰ࡢE2ࢆ10
ಸ⃰⦰ࡋࡓࠋࡇࡢ ᐃἲ࡟ࡼࡿE2ࡢᢳฟຠ⋡ࡣ80㸣࡛࠶ࡗࡓࠋ⃰ᗘ ᐃࡣ㸪ࢫࢱࣥࢲ࣮ࢻ
࠾ࡼࡧࢧࣥࣉࣝ15μl࡜100μlࡢE2࣏ࣜࢡ࣮ࣟࢼࣝᢠయ⁐ᾮ㸦AS-A㸧
㸦1㸸20,000㸧ࢆΰ࿴ࡋ4Υ
࡟࡚24᫬㛫᣺┞ࡉࡏࡓࠋࡑࡢᚋ㸪100μlࡢhorseradish peroxidase㸦1㸸150,000㸧ࢆΰ࿴ࡋ㸪4Υ
࡟࡚2᫬㛫᣺┞ࡉࡏࡓࠋE2ࡢᶆ‽᭤⥺ࡣ2㹼2,000 pg/mlࡢ⠊ᅖ࡛㸪 ᐃෆኚື࠾ࡼࡧ ᐃ㛫
ኚືࡣࡑࢀࡒࢀ6.5㸣࠾ࡼࡧ7.6%࡛࠶ࡗࡓࠋ
2㸫3㸫6㸬⤫ィฎ⌮
⤖ᯝࡣࡍ࡭࡚ᖹᆒ್sᶆ‽ㄗᕪ࡛♧ࡋࡓࠋ⾑୰ P4 ⃰ᗘ㸪୺ᖍ༸⬊ࡢᖹᆒ┤ᚄ࠾ࡼࡧ༸
⬊ቨ⾑ὶ᥎⛣ࡢẚ㍑࡟ࡣ㸪2 ඖ㓄⨨ศᩓศᯒࢆ⾜࠸㸪඲యࡢኚ໬ࡢ᭷ពᛶࢆㄪ࡭㸪஺஫
స⏝ࡀ᭷ព࡛࠶ࡗࡓࡶࡢ࡟ᑐࡋ࡚㸪Bartlet ᳨ᐃࢆ⾜࠸ศᩓࡢᆒ୍ᛶࢆ᳨ᐃࡋࡓᚋ㸪
Post-hoc ᳨ᐃ࡜ࡋ࡚ Schefe ࡢከ⩌ẚ㍑᳨ᐃࢆ⾜ࡗࡓࠋDay 8 ࡟࠾ࡅࡿ⾑୰ E2 ⃰ᗘࡢ᳨ᐃ
࡟ࡣ F ᳨ᐃ࡟ࡼࡾศᩓࡢᆒ୍ᛶࢆ᳨ᐃࡋ㸪Student ࡢ t ᳨ᐃࢆ⾜ࡗࡓࠋP < 0.1 ࢆഴྥ࠶ࡾ
࡜ࡋࠊP < 0.05 ࡛᭷ពᕪ࠶ࡾ࡜ࡋࡓࠋ
⤫ィฎ⌮࡟ࡣ⤫ィฎ⌮ࢯࣇࢺ࡛࠶ࡿ StatView㸦Abacus
Concepts㸪Inc.㸪Berkeley㸪CA㸪USA㸧ࢆ⏝࠸ࡓࠋ
2㸫4㸬ヨ㦂 3㸸W1DF ࡜ W2DF ࡟࠾ࡅࡿ᤼༸๓ࡢ༸⬊ෆࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥ⃰ᗘ࠾ࡼࡧ
㢛⢏ᒙ⣽⬊࡛Ⓨ⌧ࡋ࡚࠸ࡿᅉᏊࡢẚ㍑
16
2㸫4㸫1㸬౪ヨື≀
⮫ᗋⓗ࡟೺ᗣ࡛㸪ṇᖖ࡞Ⓨ᝟࿘ᮇࢆ᭷ࡍࡿ࣍ࣝࢫࢱ࢖ࣥ✀㠀Ἢங∵ 7 㢌㸦ᖹᆒᖺ㱋㸸
4.0 r 1.1 ṓ㸪ᖹᆒsᶆ‽ㄗᕪ) ࢆ⏝࠸ࡓࠋ ࢘ࢩࡣᖏᗈ␆⏘኱Ꮫ␆⏘ࣇ࢕࣮ࣝࢻ⛉Ꮫࢭࣥ
ࢱ࣮ෆࡢࣃࢻࢵࢡ࡟࡚㸪ࢥ࣮ࣥࢧ࢖࣮ࣞࢪ㸪஝ⲡ࠾ࡼࡧ⃰ཌ㣫ᩱࡀΰྜࡉࢀࡓ TMR ࡀ
⤥୚ࡉࢀ㸪⮬⏤㣧Ỉ࡛ࡁࡿ≧ἣ࡛㣫㣴ࡉࢀ࡚࠸ࡓࠋᐇ㦂ෆᐜࡣᖏᗈ␆⏘኱Ꮫࡢᐇ㦂೔⌮
ጤဨ఍࡟࡚ᢎㄆࡉࢀ࡚࠸ࡿࠋ
2㸫4㸫2 㸬ᐇ㦂᪉ἲ
ᐇ㦂ࡢࣉࣟࢺࢥ࣮ࣝࡣヨ㦂 2 ࡜ྠᵝ࡛࠶ࡿࠋᮏヨ㦂࡛ࡣ LH ࢧ࣮ࢪ┤๓㸦PGF2α ᢞ୚
40 ᫬㛫ᚋ㸸Day 8㸧࠾ࡼࡧ LH ࢧ࣮ࢪᚋ㸦GnRH ᢞ୚ 24 ᫬㛫ᚋ㸸Day 9㸧ࡢ୺ᖍ༸⬊ࡢᛶ
㉁ࢆヲ⣽࡟ホ౯ࡍࡿࡓࡵ㸪༸⬊ᾮ࠾ࡼࡧ㢛⢏ᒙ⣽⬊ࢆ᥇ྲྀࡋホ౯ࡋࡓࠋᮏヨ㦂࡛ࡣ௨ୗ
4 ヨ㦂⩌ࢆタࡅࡓ㸪㸯㸧LH ࢧ࣮ࢪ᭚㟢๓➨ 1 ༸⬊Ἴ⩌㸦n㸻7㸧
㸪㸰㸧LH ࢧ࣮ࢪ᭚㟢๓➨
2 ༸⬊Ἴ⩌㸦n㸻7㸧
㸪㸱㸧LH ࢧ࣮ࢪ᭚㟢ᚋ➨ 1 ༸⬊Ἴ⩌㸦n㸻6㸧
㸪㸲㸧LH ࢧ࣮ࢪ᭚㟢ᚋ
➨ 2 ༸⬊Ἴ⩌㸦n㸻6㸧࡛࠶ࡿࠋ㸯㸧࡜㸰㸧ࡢ⩌࡟ࡣࢡࣟࢫ࣮࢜ࣂ࣮ヨ㦂࡟ࡼࡾ 7 㢌ࡢ࢘
ࢩࡀ඲࡚ྵࡲࢀ࡚࠸ࡿࠋ㸱㸧࡜㸲㸧ࡢ⩌࡟㛵ࡋ࡚ࡣ 1 㢌ࡢ࢘ࢩ࡛㸪㢛⢏ᒙ⣽⬊ࡢᅇ཰㔞
ࡀᑡ࡞ࡃࠊࡑࡢ࢘ࢩࢆヨ㦂ࡼࡾ㝖እࡋࡓࡓࡵࠊ6 㢌ࢆ⏝࠸ࡓࢡࣟࢫ࣮࢜ࣂ࣮ヨ㦂࡜࡞ࡗ
࡚࠸ࡿࠋࡲࡓ㸪ࡑࢀࡒࢀࡢ⩌ࡢ࢘ࢩࡢ୺ᖍ༸⬊ࡣ඲ู࡚ࡢⓎ᝟࿘ᮇ࡛᥇ᮦࢆ⾜࡞ࡗ࡚࠸
ࡿࠋヨ㦂 3 ࡢࣉࣟࢺࢥ࣮ࣝࡢᶍᘧᅗࢆ Fig. 2.9.࡟♧ࡋࡓࠋ
2㸫4㸫3㸬୺ᖍ༸⬊ࡢ྾ᘬ࡜㢛⢏ᒙ⣽⬊ࡢᅇ཰
୺ᖍ༸⬊ࡢ྾ᘬࡣ㸪㉸㡢Ἴ⏬ീデ᩿⿦⨨㸦HS-1500㸪ᮏከ㟁Ꮚ㸪ᮾி㸪᪥ᮏ㸧ࢆ⏝࠸࡚
㉸㡢Ἴ⏬ീほᐹୗ࡛ࡢ⤒⭐༸⬊✸่࡟ࡼࡾ⾜ࡗࡓࠋ㉸㡢Ἴ⏬ീほᐹ࡟ࡣ㸪7.5MHzࡢ⭐⏝ࣉ
࣮ࣟࣈ㸦HCV-3710MV㸪ᮏከ㟁Ꮚ㸪ᮾி㸪᪥ᮏ㸧ࢆ⏝࠸࡚⾜ࡗࡓࠋࣉ࣮ࣟࣈࡢୖ㒊࡟ࡣ㸪
17
⣙40cmࡢ✸่⏝ࡢ㔪㸦ࢹ࢕ࢫ࣏࣮ࢨࣈࣝ᥇༸㔪 A-ࢱ࢖ࣉ㸪࣑ࢧ࣡་⛉ᕤᴗ㸪Ⲉᇛ㸪᪥ᮏ㸧
ࢆ⿦╔࡛ࡁࡿࡼ࠺࡟࡞ࡗ࡚࠸ࡿࠋ༸⬊྾ᘬࡢ๓‽ഛ࡜ࡋ࡚㸪⭐ෆ࠾ࡼࡧእ㝜㒊࿘㎶ࢆࡼࡃ
Ὑίࡋࡓࠋḟ࡟ࣉ࣮ࣟࣈࢆ⭐ࡼࡾᤄධࡋ㸪༸ᕢࢆ┤⭠ࡼࡾᤄධࡋࡓᡭ࡛⭐ቨ㉺ࡋ࡟ᢲࡋᙜ
࡚ࡓࠋ㉸㡢Ἴ⏬ീデ᩿⿦⨨ࡢ⏬㠃ୖ࡟ࡣ㸪᥇༸㔪ࡢ࢞࢖ࢻࣛ࢖ࣥࡀ♧ࡉࢀ࡚࠸ࡿࡢ࡛㸪ࡇ
ࡢ࢞࢖ࢻࣛ࢖ࣥୖ࡟྾ᘬࡍࡿ༸⬊ࡀᥥ෗ࡉࢀࡿࡼ࠺࡟ࡋࡓࠋ⏬ീࢆほᐹࡋ࡞ࡀࡽ㸪18Gࡢ
㔪ࢆ⭐ቨࢆ௓ࡋ࡚༸⬊⭍࡬࡜่ධࡋ㸪༸⬊ᾮ࠾ࡼࡧ㢛⢏ᒙ⣽⬊ࢆ᥇༸㔪࡟㐃⤖ࡉࡏࡓࢩࣜ
ࣥࢪ࡟ࡼࡾ྾ᘬࡋࡓࠋ ༸⬊ᾮࡣ5.0mlࢳ࣮ࣗࣈ࡟ධࢀ㸪ịỈ୰࡟࡚ᛴ෭ᚋ㸪ᐇ㦂ᐊෆࡢᐇ
య㢧ᚤ㙾ୗ࡛㢛⢏ᒙ⣽⬊ࢆᅇ཰ࡋࡓࠋ㢛⢏ᒙ⣽⬊ࡣTriPure Isolation Reagent㸦Roche
Diagnostics GmbH㸪Mannheim㸪Germany㸧1.0mlࢆຍ࠼࡚᏶඲࡟⁐ゎࡉࡏ㸪㸫80Υ࡟࡚mRNA
ᢳฟࡲ࡛ಖᏑࡋࡓࠋ㢛⢏ᒙ⣽⬊ᅇ཰ᚋ㸪༸⬊ᾮࡣ4Υ㸪500 g࡛10ศ㛫㐲ᚰࢆ⾜࠸ୖΎࢆศ
㞳ࡋࡓᚋ㸪EIA࡟ࡼࡿP4㸪E2࠾ࡼࡧ࢔ࣥࢻࣟࢫࢸࣥࢪ࢜ࣥ㸦A4㸧⃰ᗘ ᐃࡲ࡛㸫30Υ࡟࡚
෾⤖ಖᏑࡋࡓࠋ
2㸫4㸫4㸬༸⬊ᾮP4㸪E2࠾ࡼࡧA4⃰ᗘࡢ ᐃ
༸⬊ᾮࡼࡾࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥࢆᢳฟࡍࡿࡓࡵ࡟㸪⾑₢40μl࡟ࢪ࢚ࢳ࢚࣮ࣝࢸࣝ㸦㛵ᮾ
໬Ꮫ㸪ᮾி㸪᪥ᮏ㸧1.0mlࢆຍ࠼㸪ᨩᢾᶵ㸦Mix-EVR㸪ࢱ࢖ࢸࢵࢡ㸪ᇸ⋢㸪᪥ᮏ㸧ࢆ⏝࠸
࡚30ศ㛫࣎ࣝࢸࢡࢫࡋ㸪ࡑࡢᚋᐊ ࡟࡚40ศ㛫㟼⨨ࡋࡓࠋࡑࡢᚋ㸫30Υࡢ෭෾ᗜ࡟࡚⛣ື
ࡋ24᫬㛫࠿ࡅ࡚᏶඲࡟෾⤖ࡉࡏࡓࠋ෾⤖ᚋ㸪ᾮ┦㒊ศࢆ5mlヨ㦂⟶࡟ࢹ࢝ࣥࢺࡋ㸪ࢻࣛࣇ
ࢺෆࡢ࢛࣮࢘ࢱ࣮࣭ࣂࢫ࡟ᾐࡋ㸪40Υࡲ࡛ୖ᪼ࡉࡏ࡞ࡀࡽࢪ࢚ࢳ࢚࣮ࣝࢸࣝࢆ᥹Ⓨࡉࡏࡓ
ᚋ㸪50Υࡲ࡛ୖ᪼ࡉࡏ↓⮯࡟࡞ࡿࡲ࡛᏶඲࡟᥹Ⓨࡉࡏࡓࠋ᥹Ⓨᚋ㸪ヨ㦂⟶࡟࢔ࢵࢭ࢖࣭ࣂ
ࢵࣇ࢓࣮ࢆ200μlຍ࠼㸪20ศ㛫࣎ࣝࢸࢡࢫࡋࡓࠋࡇࡢᡭἲ࡟ࡼࡾ༸⬊ᾮ୰ࡢࢫࢸࣟ࢖ࢻ࣍ࣝ
ࣔࣥࢆ5ಸ࡟ᕼ㔘ࡋࡓࠋࡇࡢ ᐃἲ࡟ࡼࡿP4㸪E2࠾ࡼࡧA4ࡢᢳฟຠ⋡ࡣࡑࢀࡒࢀ82㸣㸪81㸣
࠾ࡼࡧ85㸣࡛࠶ࡗࡓࠋ
P4࠾ࡼࡧE2ࡢ⃰ᗘ ᐃࡣ❶ࡢ2㸫2㸫5.࠾ࡼࡧ2㸫3㸫5.࡛グࡋࡓ࡜࠾ࡾ
18
࡛࠶ࡿࠋP4ࡢ ᐃෆኚື࠾ࡼࡧ ᐃ㛫ኚືࡣࡑࢀࡒࢀ5.5%࠾ࡼࡧ7.4%㸪E2ࡢ ᐃෆኚື࠾
ࡼࡧ ᐃ㛫ኚືࡣ6.2㸣࠾ࡼࡧ8.6%࡛࠶ࡗࡓࠋA4ࡢ⃰ᗘ ᐃࡣࢫࢱࣥࢲ࣮ࢻ࠾ࡼࡧࢧࣥࣉ
ࣝ15μl࡜100μlࡢA4࣏ࣜࢡ࣮ࣟࢼࣝᢠయ⁐ᾮ㸦A-3-CMO-BSA㸪ࢥࢫ࣭ࣔࣂ࢖࢜㸪ᮾி㸪᪥
ᮏ㸧㸦1㸸750,000㸧࡜100μlࡢA-3-CMO-horseradish peroxidase㸦ࢥࢫ࣭ࣔࣂ࢖࢜㸪ᮾி㸪᪥
ᮏ㸧㸦1㸸500,000㸧ࢆΰ࿴ࡋ4Υ࡟࡚24᫬㛫᣺┞ࡉࡏࡓࠋA4ࡢᶆ‽᭤⥺ࡣ7.8㹼8,000 pg/ml
ࡢ⠊ᅖ࡛㸪 ᐃෆኚື࠾ࡼࡧ ᐃ㛫ኚືࡣࡑࢀࡒࢀ4.3㸣࠾ࡼࡧ5.2%࡛࠶ࡗࡓࠋ
2㸫4㸫5㸬RNAᢳฟ࡜ࣜ࢔ࣝࢱ࢖࣒PCR
Total RNAࡢᢳฟࡣ௨ୗࡢᡭ㡰࡛⾜ࡗࡓࠋゎ෾ࡋࡓࢧࣥࣉࣝ࡟ࢡ࣒ࣟࣟ࣍ࣝ⁐ᾮࢆ200μl
ຍ࠼࡚㸪15⛊㛫࣎ࣝࢸࢡࢫࡋ3ศ㛫ᐊ ࡛㟼⨨ࡋࡓᚋ㸪4Υ㸪36,000 g࡟࡚15ศ㛫㐲ᚰศ㞳
ࢆ⾜ࡗࡓࠋࢡ࣒ࣟࣟ࣍ࣝᾮ┦࡜TriPure Isolation Reagent ⁐ᾮ┦࡟ศ㞳ࡋ࡚࠸ࡿࡇ࡜ࢆ☜ㄆ
ࡋ㸪ࢡ࣒ࣟࣟ࣍ࣝᒙࢆูࡢ1.5mlࢳ࣮ࣗࣈ࡟⛣ࡍࠋࡇࢀ࡟500μlࡢ࢖ࢯࣉࣟࣃࣀ࣮ࣝ⁐ᾮ
㸦3-Propanol㸧ࢆຍ࠼㸪15⛊㛫࣎ࣝࢸࢡࢫࡋ㸪10ศ㛫ᐊ ࡟࡚㟼⨨ࡋࡓᚋ㸪4Υ㸪36,000 g
࡟࡚15ศ㛫㐲ᚰศ㞳ࢆ⾜ࡗࡓࠋRNAࡢ࣌ࣞࢵࢺࡢᏑᅾࢆ☜ㄆࡋࡓᚋ㸪࢖ࢯࣉࣟࣃࣀ࣮ࣝ⁐
ᾮࢆ㝖ཤࡋ㸪500μlࡢ80㸣࢚ࢱࣀ࣮ࣝࢆຍ࠼㸪Ὑίࡋ㸪4Υ㸪36,000 g࡟࡚5ศ㛫㐲ᚰศ㞳ࢆ
⾜ࡗࡓࠋ࢚ࢱࣀ࣮ࣝࢆ㝖ཤᚋ㸪ᐊ ࡛5ศ㛫࣌ࣞࢵࢺࢆ஝⇱ࡉࡏ㸪6μlࡢࢪ࢚ࢳࣝࣆ࣮ࣟ࢝
࣎ࢿ࣮ࢺ㸦DEPC㸧ฎ⌮Ỉࢆຍ࠼ࡓࠋ
㏫㌿෗ࡣSuperscript VIRO Reaction Mix 㸦Invitrogen.㸪Carlsbad㸪CA㸪USA㸧ࢆ⏝࠸ࡓࠋ
ࡲࡎ㸪Nano-Drop 2000㸦Thermo scientific㸪Wilmington㸪DE㸪USA㸧ࢆ⏝࠸࡚RNA⃰ᗘࢆ⟬
ฟࡋࡓࠋḟ࡟㸪RQ1 RNase-Free DNase (Promega㸪Madison㸪WI㸪USA) ࢆ⏝࠸࡚DNaseฎ
⌮ࢆ⾜ࡗࡓࠋRNAࡀ1μgྵࡲࢀࡿRNA⁐ᾮ㸪1μlࡢDNase 10×Reaction Buffer࠾ࡼࡧ2μlࡢ
RNase-Free DNaseࢆΰ࿴ࡋ㸪37Υ࡛30ศ㛫࢖࣮ࣥ࢟ࣗ࣋ࢺࡋࡓࠋࡑࡢᚋ㸪1μlࡢDNase Stop
Solutionࢆຍ࠼65Υ࡛10ศ㛫࢖࣮ࣥ࢟ࣗ࣋ࢺࡋࡓࠋDNaseฎ⌮ࡋࡓࢧࣥࣉࣝ࡟5×VILO
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Reaction Mixࢆ4μl㸪10×Super Script Enzymeࢆ2μlຍ࠼㸪⥲㔞ࡀ20μl࡟࡞ࡿࡼ࠺࡟DEPCฎ⌮
Ỉࢆຍ࠼ࡓᚋ㸪25Υ࡛10ศ㛫㸪42Υ࡛60ศ㛫࠾ࡼࡧ85Υ࡛5ศ㛫࢖࣮ࣥ࢟ࣗ࣋ࢺࡋ㸪cDNA
ࢆసᡂࡋࡓࠋ
2㸫4㸫6㸬ࣜ࢔ࣝࢱ࢖࣒PCR࡟ࡼࡿmRNAⓎ⌧㔞ࡢ ᐃ
ࣜ࢔ࣝࢱ࢖࣒PCRࡣTli RNaseH Plus㸦࢟࢔ࢤࣥ㸪ᮾி㸪᪥ᮏ㸧ࢆ౑⏝ࡋ㸪Roter-Gene Q 㸦࢟
࢔ࢤࣥ㸪ᮾி㸪᪥ᮏ㸧 ࢆ⏝࠸࡚⾜ࡗࡓࠋ7.5μlࡢSYBR Green Master Mix㸪5.75μlࡢDEPCฎ
⌮Ỉ㸪Forward࡜Reverseࡢࣉࣛ࢖࣐࣮ࢆྛ0.375μlຍ࠼㸪᭱ᚋ࡟1.0μlࡢࢧࣥࣉࣝࢆຍ࠼࡚཯
ᛂࡉࡏࡓࠋ ᐃࡍࡿmRNAࡣ㸪LHཷᐜయ㸦LHr㸧㸪࢔࣐ࣟࢱ࣮ࢮ㸦CYP19A1㸧㸪ࢩࢡࣟ࢜
࢟ࢩࢤࢼ࣮ࢮ̺2㸦COX-2㸧㸪PGE2ྜᡂ㓝⣲㸦PGES㸧㸪PGF2αྜᡂ㓝⣲㸦PGFS㸧㸪ㄏᑟᆺ
୍㓟໬❅⣲ྜᡂ㓝⣲㸦iNOS㸧㸪⾑⟶ෆ⓶ᆺ୍㓟໬❅⣲ྜᡂ㓝⣲㸦eNOS㸧㸪⾑⟶ෆ⓶ቑṪ
ᅉᏊ㸦VEGF㸧120㸪VEGF164㸪⥺⥔ⱆ⣽⬊ቑṪᅉᏊ㸦FGF㸧-2㸪Steroidogenic acute regulatory
protein㸦StAR㸧㸪ࢳࢺࢡ࣮࣒ࣟP450ഃ㙐ษ᩿㓝⣲㸦cytochrome P450 cholesterol side-chain
cleavage enzymes㸹 P450-scc㸧㸪3β-Ỉ㓟ᇶ⬺Ỉ⣲㓝⣲㸦3β-hydroxy steroid dehydrogenase㸹
3β-HSD㸧࠾ࡼࡧࢢࣜࢭࣝ࢔ࣝࢹࣄࢻ3ࣜࣥ㓟⬺Ỉ⣲㓝⣲㸦glyceraldehyde-3-phosphate
dehydrogenase㸹GAPDH㸧࡛࠶ࡿࠋGAPDHࡣෆ㒊ᶆ‽㑇ఏᏊ࡜ࡋ࡚⏝࠸㸪ࡑࡢⓎ⌧࡜ࡢ๭
ྜ࡛ồࡵࡓࠋࣉࣛ࢖࣐࣮ࡣPrimer-3ࢆ⏝࠸࡚సᡂࡋࡓࠋࣜ࢔ࣝࢱ࢖࣒PCRࡢ཯ᛂ᮲௳ࡣ94Υ
࡛10ศ㛫ฎ⌮ࡋࡓᚋ㸪94Υ࡛30⛊㸪ྛࠎࡢ࢔ࢽ࣮ࣜࣥࢢ ᗘ࡛30⛊࠾ࡼࡧ72Υ࡛30⛊ࡢࢧ
࢖ࢡࣝࢆ40ᅇ⾜ࡗࡓࠋࡑࢀࡒࢀࡢmRNAࡢࣉࣛ࢖࣐࣮ࡢࢩ࣮ࢡ࢚ࣥࢫࢆ♧ࡋࡓ⾲ࢆTable
2.3.࡟♧ࡋࡓࠋLHࢧ࣮ࢪ᭚㟢๓ࡢ㢛⢏ᒙ⣽⬊࡟ᑐࡋ࡚ࡣLHr࠾ࡼࡧCYP19A1 mRNAⓎ⌧㔞
ࢆ ᐃࡋࡓࠋLHࢧ࣮ࢪ᭚㟢ᚋࡢ㢛⢏ᒙ⣽⬊࡟ᑐࡋ࡚ࡣCOX-2㸪PGES㸪PGFS㸪iNOS㸪eNOS㸪
VEGF120㸪VEGF164㸪FGF-2㸪StAR㸪P450-scc࠾ࡼࡧ3β-HSD mRNAⓎ⌧㔞ࢆ ᐃࡋࡓࠋ
20
2㸫4㸫7㸬⤫ィฎ⌮
⤖ᯝࡣࡍ࡭࡚ᖹᆒ್sᶆ‽ㄗᕪ࡛♧ࡋࡓࠋ༸⬊ᾮ୰ࡢᛶࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥ⃰ᗘ࠾ࡼ
ࡧ㢛⢏ᒙ⣽⬊࡛Ⓨ⌧ࡍࡿ mRNA Ⓨ⌧㔞ࡢẚ㍑࡟㛵ࡋ࡚ࡣ㸪ࡲࡎ F ᳨ᐃ࡟ࡼࡾศᩓࡢᆒ୍
ᛶࢆ᳨ᐃࡋ㸪➼ศᩓࡀㄆࡵࡽࢀࡓሙྜ㸪Student ࡢ t ᳨ᐃࢆ⾜࠸㸪➼ศᩓࡀㄆࡵࡽࢀ࡞࠿
ࡗࡓሙྜࡣ Mann–Whitney ࡢ U ᳨ᐃࢆ⾜ࡗࡓࠋP < 0.1 ࢆഴྥ࠶ࡾ࡜ࡋࠊP < 0.05 ࡛᭷ព
ᕪ࠶ࡾ࡜ࡋࡓࠋ⤫ィฎ⌮࡟ࡣ⤫ィฎ⌮ࢯࣇࢺ࡛࠶ࡿ StatView㸦Abacus Concepts㸪Inc.㸪
Berkeley㸪CA㸪USA㸧ࢆ⏝࠸ࡓࠋ
2㸫5㸬ヨ㦂 4㸸W1DF ࡜ W2DF ࡢ᤼༸ᚋ࡟ᙧᡂࡉࢀࡿ㯤యࡢᙧែ㸪㯤య⾑ὶ࠾ࡼࡧ⾑୰
P4 ⃰ᗘ᥎⛣ࡢẚ㍑
2㸫5㸫1㸬౪ヨື≀
⮫ᗋⓗ࡟೺ᗣ࡛㸪ṇᖖ࡞Ⓨ᝟࿘ᮇࢆ᭷ࡍࡿ࣍ࣝࢫࢱ࢖ࣥ✀㠀Ἢங∵ 6 㢌㸦ᖹᆒᖺ㱋㸸
4.2 r 2.1 ṓ㸪ᖹᆒsᶆ‽ㄗᕪ) ࢆ⏝࠸ࡓࠋ ࢘ࢩࡣᖏᗈ␆⏘኱Ꮫ␆⏘ࣇ࢕࣮ࣝࢻ⛉Ꮫࢭࣥ
ࢱ࣮ෆࡢࣃࢻࢵࢡ࡟࡚㸪ࢥ࣮ࣥࢧ࢖࣮ࣞࢪ㸪஝ⲡ࠾ࡼࡧ⃰ཌ㣫ᩱࡀΰྜࡉࢀࡓ TMR ࡀ
⤥୚ࡉࢀ㸪⮬⏤㣧Ỉ࡛ࡁࡿ≧ἣ࡛㣫㣴ࡉࢀ࡚࠸ࡓࠋᐇ㦂ෆᐜࡣᖏᗈ␆⏘኱Ꮫࡢᐇ㦂೔⌮
ጤဨ఍࡟࡚ᢎㄆࡉࢀ࡚࠸ࡿࠋ
2㸫5㸫2 㸬ᐇ㦂᪉ἲ
6 㢌ࡢ࢘ࢩࡣ W1DF ᤼༸ᚋ㯤య㸦W1CL㸹n㸻3㸧࡜ W2DF ᤼༸ᚋ㯤య㸦W2CL㸹n㸻3㸧
࡟ศࡅࡓࠋࡑࢀࡒࢀࡢ⩌ࡣヨ㦂⤊஢ 2 ࠿᭶ᚋ࡟㸪ࣛࢸࣥ᱁Ꮚἲࢆ⏝࠸࡚ࢡࣟࢫ࣮࢜ࣂ࣮
ヨ㦂ࢆ⾜ࡗࡓࠋࡑࡢࡓࡵ㸪ࡑࢀࡒࢀࡢ⩌࡟ࡣ 6 㢌ࡢ࢘ࢩࡀ඲࡚ྵࡲࢀ࡚࠸ࡿ㸦n㸻6㸧
ࠋ
21
ヨ㦂ࡢࣉࣟࢺࢥ࣮ࣝࡣヨ㦂 2 ࡜ྠᵝ࡛࠶ࡿࡀ㸪ᮏヨ㦂࡛ࡣ୺ᖍ༸⬊ࢆ྾ᘬࡏࡎ㸪᤼༸
ࡉࡏ㸪ࡑࡢᚋ࡟ᙧᡂࡉࢀࡿ㯤యࢆほᐹࡋࡓࠋ
W1DF ࡜ W2DF ࡜ࡶ࡟㸪Day 8 ࡟ GnRH ࢆᢞ୚ࡋ㸪ࡑࡢ 24 ᫬㛫࠾ࡼࡧ 36 ᫬㛫ᚋ࡟㉸
㡢Ἴ⏬ീデ᩿⿦⨨࡛᤼༸☜ㄆࢆ⾜࠸㸪24 ᫬㛫ᚋ࡟᤼༸ࡏࡎ㸪36 ᫬㛫ᚋࡲ࡛࡟᤼༸ࡀ☜ㄆ
ࡉࢀࡓ᫬Ⅼࢆ Day 10 ࡜ࡋࡓࠋDay 9 ࡟࠾ࡅࡿ୺ᖍ༸⬊ࡢᖹᆒ┤ᚄ࠾ࡼࡧ༸⬊ቨ⾑ὶ㸪Day
12㸪15㸪18 ࠾ࡼࡧ 21 ࡟࠾ࡅࡿ㯤యࡢ㯤య᩿㠃✚࠾ࡼࡧ㯤య⾑ὶࢆ࣮࢝ࣛࢻࣉࣛ㉸㡢Ἴ
⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚ ᐃࡋࡓࠋ
ࡲࡓ Day 10㹼21 ࡢ㛫㸪1 ᪥࡟ 1 ᅇṇ୰ᑿ㟼⬦ࡼࡾ᥇⾑ࢆ⾜ࡗࡓࠋヨ㦂 4 ࡢࣉࣟࢺࢥ࣮
ࣝࡢᶍᘧᅗࢆ Fig. 2.15.࡟♧ࡋࡓࠋ
2㸫5㸫3㸬༸⬊࠾ࡼࡧ㯤యᙧែࡢほᐹ
Day 9࡟࠾ࡅࡿ୺ᖍ༸⬊ࡢᖹᆒ┤ᚄ࠾ࡼࡧ༸⬊ቨ⾑ὶ㸪Day 12㸪15㸪18࠾ࡼࡧ21࡟࠾ࡅ
ࡿ㯤యࡢ᩿㠃✚࠾ࡼࡧ㯤య⾑ὶࡣ㸪8.0MHzࡢࣜࢽ࢔ࣉ࣮ࣟࣈ㸦1739̺RSࣉ࣮ࣟࣈ㸹GEᶓ
Ἑ࣓ࢹ࢕࢝ࣝࢩࢫࢸ࣒㸪ᮾி㸪᪥ᮏ㸧ࢆ᥋⥆ࡋࡓ࣮࢝ࣛࢻࣉࣛ㉸㡢Ἴ⏬ീデ᩿⿦⨨㸦LOGIQ
Book XP㸪GE࣓ࢹ࢕࢝ࣝࢩࢫࢸ࣒㸪ᮾி㸪᪥ᮏ㸧ࢆ⏝࠸࡚࣮࣮࢝ࣛࣔࢻ࡟ࡼࡾほᐹࢆ⾜ࡗ
ࡓࠋ༸⬊ࡢホ౯ࡣヨ㦂1࡜ྠᵝࡢ᪉ἲ࡛⾜࠸㸪༸⬊ቨ⾑ὶࡢホ౯࡟ࡣBF㸣ࢆ⏝࠸ࡓࠋ㯤య
ࡢ᩿㠃✚ࡣ㸪㯤యࡢ᩿ᒙ⏬ീࡀ᭱኱࡟࡞ࡿࡼ࠺㟼Ṇ⏬ࢆグ㘓ࡋ㸪ࣃࢯࢥࣥୖ࡟㟼Ṇ⏬ࢆ⛣
ືࡉࡏ㸪㯤యࡢ㛗ᚄ࡜▷ᚄࡢᖹᆒ್࠿ࡽᖹᆒ┤ᚄࢆ⟬ฟࡋ㸪㸦ᖹᆒ┤ᚄ㸭2㸧2×3.14࡟ᙜ࡚
ࡣࡵ㯤య᩿㠃✚ࢆ⟬ฟࡋ㸪ࢹ࣮ࢱ࡟⏝࠸ࡓࠋ
㯤య⾑ὶࡢ᳨ᰝ᪉ἲࡣ㸪㯤యࡢ᩿ᒙീࢆほᐹࡋ㸪㯤య᩿㠃✚ࡀ᭱኱࡛࠿ࡘ⾑ὶ㠃✚ࡀ᭱
኱࡟࡞ࡿࡼ࠺࡞㟼Ṇ⏬ࢆグ㘓ࡋ㸪㯤య⾑ὶ㠃✚ࢆ⟬ฟࡋࡓࠋ
㯤య⾑ὶ㠃✚ࡢ⟬ฟࡣ㸪グ㘓ࡋࡓ᧜ᙳ⏬ീࢆࣃࢯࢥࣥෆ࡟ྲྀࡾ㎸ࡳ㸪Photoshop 5.5
㸦Adobe Systems Inc.㸪San Jose㸪CA㸪USA㸧ࢆ⏝࠸࡚⾑ὶ㡿ᇦࢆⓑ㯮⏬ീ࡟ኚ᥮ࡋ㸪Pop
22
Imaging㸦ࢹࢪࢱ࣭ࣝࣅ࣮࢖ࣥࢢ࣭࢟ࢵࢬ㸪⚄ዉᕝ㸧ࢆ⏝࠸࡚⾑ὶ㠃✚ࢆ⟬ฟࡋ㸪㯤య⾑
ὶ㠃✚࡜ࡋ࡚ࢹ࣮ࢱࢆ⏝࠸ࡓࠋ
2㸫5㸫4㸬᥇⾑
ヨ㦂ᮇ㛫୰ࡢDay 10㹼21࡟21G᥇⾑㔪࡜࣊ࣃࣜࣥຍ┿✵᥇⾑⟶㸦࣋ࣀࢪ࢙ࢡࢺϩ┿✵᥇
⾑⟶㸪TERUMO㸪ᮾி㸧ࢆ⏝࠸࡚ᑿ㟼⬦ࡼࡾ10mlࡢ᥇⾑ࢆ⾜ࡗࡓࠋ᥇ྲྀࡋࡓ⾑ᾮࡣịỈ
୰࡟࡚ᛴ෭ᚋ㸪4Υ࡛2,000 g㸪20ศ㛫㐲ᚰࡋ㸪⾑₢ศ㞳ᚋ㸪⾑୰P4⃰ᗘ ᐃࡲ࡛㸫30Υ࡟
࡚෾⤖ಖᏑࡋࡓࠋ
2㸫5㸫5㸬⾑୰P4⃰ᗘࡢ ᐃ
⾑୰P4⃰ᗘࡢ ᐃࡣヨ㦂1࡜ྠᵝࡢ᪉ἲ࡛⾜ࡗࡓࠋ ᐃෆኚື࠾ࡼࡧ ᐃ㛫ኚືࡣࡑࢀ
ࡒࢀ6.4㸣࠾ࡼࡧ8.6%࡛࠶ࡗࡓࠋ
2㸫5㸫6㸬⤫ィฎ⌮
⤖ᯝࡣࡍ࡭࡚ᖹᆒ್sᶆ‽ㄗᕪ࡛♧ࡋࡓࠋ㯤య᩿㠃✚㸪㯤య⾑ὶ㠃✚࠾ࡼࡧ⾑୰ P4
⃰ᗘ᥎⛣ࢆẚ㍑ࡍࡿ࡟ᙜࡓࡗ࡚ࡣ㸪2 ඖ㓄⨨ศᩓศᯒࢆ⾜࠸㸪඲యࡢኚ໬ࡢ᭷ពᛶࢆㄪ
࡭㸪஺஫స⏝ࡀ᭷ព࡛࠶ࡗࡓሙྜ㸪Bartlet ᳨ᐃࢆ⾜࠸ศᩓࡢᆒ୍ᛶࢆ᳨ᐃࡋࡓᚋ㸪Post-hoc
᳨ᐃ࡜ࡋ࡚ Schefe ࡢከ⩌ẚ㍑᳨ᐃࢆ⏝࠸ࡓࠋ᤼༸๓༸⬊ࡢᖹᆒ┤ᚄࢆẚ㍑ࡍࡿ࡟ࡣ㸪ࡲ
ࡎ F ᳨ᐃ࡟ࡼࡾศᩓࡢᆒ୍ᛶࢆ☜ㄆࡋࡓᚋ㸪Student ࡢ t ᳨ᐃࢆ⾜ࡗࡓࠋP < 0.1 ࢆഴྥ࠶
ࡾ࡜ࡋࠊP < 0.05 ࡛᭷ពᕪ࠶ࡾ࡜ࡋࡓࠋ⤫ィฎ⌮࡟ࡣ⤫ィฎ⌮ࢯࣇࢺ࡛࠶ࡿ StatView
㸦Abacus Concepts㸪Inc.㸪Berkeley㸪CA㸪USA㸧ࢆ⏝࠸ࡓࠋ
2㸫6㸬⤖ᯝ
23
2㸫6㸫1㸬ヨ㦂1ࡢ⤖ᯝ
⾑୰P4⃰ᗘ᥎⛣ࢆFig. 2.3.࡟♧ࡋࡓࠋ඲ヨ㦂ᮇ㛫୰࡟࠾࠸࡚W2⩌࡛W1⩌࡟ẚ㍑ࡋ࡚᭷ព
࡟㧗ࡃ᥎⛣ࡋࡓࠋ
୺ᖍ༸⬊ࡢᖹᆒ┤ᚄࡢ᥎⛣ࢆFig. 2.4.࡟♧ࡋࡓࠋW1DFࡢᖹᆒ┤ᚄࡣヨ㦂ᮇ㛫୰㸪W2DF
࡟ẚ㍑ࡋ࡚኱ࡁࡃⓎ⫱ࡋ㸪≉࡟Day 6࡟᭷ព࡟኱ࡁ࠿ࡗࡓࠋࡲࡓ㸪W1DF⩌ෆ࡛ࡣ㸪Day 3
࠾ࡼࡧ4࠿ࡽDay 6࡟࠿ࡅ࡚᭷ព࡟኱ࡁࡃⓎ⫱ࡋࡓࡀ㸪W2DF⩌ෆ࡛ࡣ㸪Day 3࠿ࡽDay 6࡟
࠿ࡅ࡚ࡢࡳ᭷ព࡟኱ࡁࡃ࡞ࡗࡓࠋ
Day 6࡟࠾ࡅࡿBFA࠾ࡼࡧBF㸣ࢆTable 2.1.࡟♧ࡋࡓࠋBFA࠾ࡼࡧBF%ࡣW1DF࡛㧗࠸ഴ
ྥࢆ♧ࡋࡓࠋ
2㸫6㸫2㸬ヨ㦂2ࡢ⤖ᯝ
୺ᖍ༸⬊ࡢᖹᆒ┤ᚄࡢ᥎⛣ࢆFig. 2.6.࡟♧ࡋࡓࠋᖹᆒ┤ᚄࡢ᥎⛣ࡣ㸪W1DFࡀW2DF࡟ẚ
㍑ࡋ࡚ヨ㦂ᮇ㛫୰ࢆ㏻ࡋ࡚᭷ព࡟㧗ࡃ᥎⛣ࡋࡓࠋヨ㦂ᮇ㛫୰ࡢ⾑୰P4⃰ᗘ᥎⛣ࢆFig. 2.7.
࡟♧ࡋࡓࠋDay 6࡟࠾ࡅࡿ⾑୰P4⃰ᗘࡣW2DF࡛W1DF࡟ẚ㍑ࡋ࡚᭷ព࡟㧗࠿ࡗࡓࡀ㸪ࡑࡢ
ᚋࡢ⾑୰P4⃰ᗘ᥎⛣࡟୧⩌㛫࡛ᕪࡣ࡞ࡃ㸪PGF2Dᢞ୚ᚋᛴ⃭࡟పୗࡋࡓࠋ
ヨ㦂ᮇ㛫୰ࡢBFA࠾ࡼࡧBF%ࡢ᥎⛣ࢆFig. 2.8.࡟♧ࡋࡓࠋBFAࡣ㸪W1DF࡟࠾࠸࡚Day 9
࡛W2DF࡟ẚ㍑ࡋ࡚᭷ព࡟㧗࠿ࡗࡓࡀ㸪Day 6࠾ࡼࡧ8࡛ࡣ୧⩌㛫࡛ᕪࡣ࡞࠿ࡗࡓࠋࡲࡓ㸪
BFAࡢ᥎⛣ࢆ⩌ෆ࡛ẚ㍑ࡋࡓ࡜ࡇࢁW1DF࠾ࡼࡧW2DF࡜ࡶ࡟Day 6࠿ࡽ9࡟࠿ࡅ࡚᭷ព࡟
ቑຍࡋࡓࠋࡲࡓ㸪W1DF࡟࠾࠸࡚ࡢࡳDay 8࠿ࡽ9࡟࠿ࡅ࡚᭷ព࡟ቑຍࡋࡓࡀ㸪W2DF࡛ࡣ
᭷ព࡞ቑຍࡣࡳࡽࢀ࡞࠿ࡗࡓࠋBF㸣ࡣ㸪W1DF࡟࠾࠸࡚Day 9࡛W2DF࡟ẚ㍑ࡋ࡚᭷ព࡟㧗
࠿ࡗࡓࡀ㸪Day 6࠾ࡼࡧ8࡛ࡣ୧⩌㛫࡛ᕪࡣ࡞࠿ࡗࡓࠋBF㸣᥎⛣ࢆ⩌ෆ࡛ẚ㍑ࡋࡓ࡜ࡇࢁ
24
W1DF࡛ࡣDay 6࠿ࡽ9࠾ࡼࡧDay 8࠿ࡽ9࡟࠿ࡅ࡚᭷ព࡟ቑຍࡋࡓࡀ㸪W2DF࡛ࡣ᭷ព࡞ቑ
ຍࡣࡳࡽࢀ࡞࠿ࡗࡓࠋ
Day 8࡟࠾ࡅࡿ⾑୰E2⃰ᗘࢆTable 2.2.࡟♧ࡋࡓࠋ⾑୰E2⃰ᗘࡣW1DF࡛᭷ព࡟㧗࠿ࡗࡓࠋ
2㸫6㸫3㸬ヨ㦂3ࡢ⤖ᯝ
LHࢧ࣮ࢪ᭚㟢๓࡟࠾ࡅࡿ༸⬊ᾮ୰E2࠾ࡼࡧA4⃰ᗘࡣ㸪W1DF࡛᭷ព࡟㧗࠿ࡗࡓࡀ㸪P4
⃰ᗘ࡟ᕪࡣ࡞࠿ࡗࡓ㸦Table 2.4.㸧ࠋLHࢧ࣮ࢪ᭚㟢ᚋ࡟࠾ࡅࡿ㸪༸⬊ᾮ୰P4࠾ࡼࡧE2⃰ᗘ࡟
ᕪࡣ࡞࠿ࡗࡓ㸦Table 2.5.㸧ࠋ
LHr࡜CYP19A1 mRNAⓎ⌧㔞ࡢ⤖ᯝࢆFig. 2.10.࡟♧ࡋࡓࠋLHrࡣW1DF࡛W2DF࡟ẚ㍑ࡋ
࡚᭷ព࡟㧗࠿ࡗࡓࡀ㸪CYP19AⓎ⌧㔞࡟ᕪࡣ࡞࠿ࡗࡓࠋCOX-2㸪PGES࠾ࡼࡧPGFS mRNA
Ⓨ⌧㔞࡟୧⩌㛫࡛ᕪࡣ࡞࠿ࡗࡓ㸦Fig. 2.11㸧ࠋiNOS࠾ࡼࡧeNOS mRNAⓎ⌧㔞ࢆFig. 2.12.
࡟♧ࡋࡓࠋiNOS ࡟ᕪࡣ࡞࠿ࡗࡓࡀ㸪eNOSࡣW1DF࡛㧗࠸ഴྥࢆ♧ࡋࡓࠋVEGF120㸪
VEGF164࠾ࡼࡧFGF-2 mRNAⓎ⌧㔞ࡢ⤖ᯝࢆFig. 2.13.࡟♧ࡋࡓࠋW1DF࡟࠾࠸࡚㸪VEGF120
࠾ࡼࡧFGF-2࡛㧗࠸ഴྥࢆ♧ࡋ㸪VEGF164ࡣ᭷ព࡟㧗࠿ࡗࡓࠋStAR㸪P450-scc࠾ࡼࡧ3β-HSD
mRNAⓎ⌧㔞ࡢ⤖ᯝࢆFig. 2.14.࡟♧ࡋࡓࠋW1DF࡟࠾࠸࡚StAR࡛㧗࠸ഴྥࢆ♧ࡋ㸪P450-scc
࠾ࡼࡧ3β-HSD mRNAࡣ᭷ព࡟㧗࠿ࡗࡓࠋ
2㸫6㸫4㸬ヨ㦂4ࡢ⤖ᯝ
Day 9࡟࠾ࡅࡿW1DF࡜W2DFࡢᖹᆒ┤ᚄ࡜BF㸣ࡢ⤖ᯝࢆTable 2.6.࡟♧ࡋࡓࠋW1DF࡟࠾
࠸࡚ᖹᆒ┤ᚄ࠾ࡼࡧBF%ࡣ኱ࡁ࠿ࡗࡓࠋ㯤య᩿㠃✚᥎⛣ࢆFig. 2.16.࡟♧ࡋࡓࠋ㯤య᩿㠃✚
ࡣDay 15㸪18࠾ࡼࡧ21࡛W1CL࡛W2CL࡟ẚ㍑ࡋ࡚᭷ព࡟㧗࠿ࡗࡓࠋ
25
㯤య⾑ὶ㠃✚᥎⛣ࢆFig. 2.17.࡟♧ࡋࡓࠋ㯤య⾑ὶ㠃✚ࡣDay 12࠾ࡼࡧ15࡛W1CL࡛W2CL
࡟ẚ㍑ࡋ࡚᭷ព࡟㧗࠿ࡗࡓࠋ
⾑୰P4⃰ᗘ᥎⛣ࢆFig .2.18.࡟♧ࡋࡓࠋ⾑୰P4⃰ᗘࡣ඲ヨ㦂ᮇ㛫ࢆ㏻ࡌ࡚W1CL࡛W2CL࡟
ẚ㍑ࡋ࡚᭷ព࡟㧗࠿ࡗࡓࠋ
2㸫7㸬⪃ᐹ
ᮏ❶࡛ࡢヨ㦂 1 ࠾ࡼࡧ 2 ࠿ࡽ㸪W1DF ࡣ W2DF ࡟ẚ㍑ࡋ࡚㸪୺ᖍ༸⬊ࡢᖹᆒ┤ᚄ㸪༸
⬊ቨ⾑ὶ㸪LH ࢧ࣮ࢪ᭚㟢┤๓ࡢ⾑୰ E2 ⃰ᗘࡀ㧗࠿ࡗࡓࠋࡲࡓ㸪ヨ㦂 3 ࠿ࡽ㸪༸⬊ᾮ E2
⃰ᗘ࠾ࡼࡧ༸⬊ᾮ A4 ⃰ᗘ㸪㢛⢏ᒙ⣽⬊࡛Ⓨ⌧ࡋ࡚࠸ࡿ LHr㸪⾑⟶᪂⏕ᅉᏊ㸪ࢫࢸࣟ࢖ࢻ
ྜᡂ㓝⣲ࡢ mRNA Ⓨ⌧㔞ࡀ W1DF ࡛㧗࠿ࡗࡓࠋヨ㦂 4 ࠿ࡽ㸪W1DF ᤼༸ᚋ࡟ᙧᡂࡉࢀ
ࡿ㯤యࡢ᩿㠃✚㸪⾑ὶ࠾ࡼࡧ⾑୰ P4 ⃰ᗘ᥎⛣ࡀ㧗࠸ࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋࡇࢀࡽࡢ⤖
ᯝ࠿ࡽ㸪W1DF ࡣ W2DF ࡟ẚ㍑ࡋ࡚༸⬊࡜ࡋ࡚ࡼࡾᶵ⬟ⓗ࡟άຊࡀ㧗࠸ࡇ࡜ࡀ⪃࠼ࡽࢀ
ࡿࠋࡲࡓ㸪ࡇࢀࡽࡢᕪ␗ࡀ⏕ࡌࡿཎᅉ࡜ࡋ࡚㸪W1DF Ⓨ⫱ᮇ㛫୰ࡢప࠸⾑୰ P4 ⃰ᗘ࡟క
࠺㧗࠸ LH ࣃࣝࢫ㢖ᗘ࡟ࡼࡿ༸⬊⣽⬊࡬ࡢ่⃭ࡀ᥎ ࡉࢀࡓࠋ
ヨ㦂 1 ࡼࡾ㸪༸⬊ἼⓎ⌧㛤ጞ࠿ࡽ 7 ᪥┠ࡲ࡛ࡢ୺ᖍ༸⬊ࡢⓎ⫱ࢆẚ㍑ࡍࡿ࡜㸪༸⬊㑅
ᢤ㛤ጞᚋ࠿ࡽ㸪Ⓨ⫱⋡ࡸ୺ᖍ༸⬊ࡢᖹᆒ┤ᚄࡣ W1DF ࡛኱ࡁࡃ࡞ࡿࡇ࡜ࡀ♧ࡉࢀࡓࠋࡲ
ࡓ㸪W1DF ࠾ࡼࡧ W2DF ࡑࢀࡒࢀࡢⓎ⫱ᮇ㛫୰ࡢ⾑୰ P4 ⃰ᗘࢆẚ㍑ࡍࡿ࡜㸪Day 0 ࠿ࡽ
Day 6 ࡟࠿ࡅ࡚ W1DF ࡛᭷ព࡟పࡃ᥎⛣ࡍࡿࡇ࡜ࡀ᫂ࡽ࠿࡟ࡉࢀࡓࠋ㐣ཤࡢ◊✲࡟࠾࠸
࡚㸪㯤యᙧᡂᮇࡣ㯤య㛤ⰼᮇ࡟ẚ㍑ࡋ࡚㸪LH ࣃࣝࢫ㢖ᗘࡀ㧗ࡃ࡞ࡿࡇ࡜ࡀሗ࿌ࡉࢀ࡚
࠸ࡿ㸦73㸧
ࠋࡲࡓ㸪⭐ෆ␃⨨ᆺ P4 〇๣ࢆ⏝࠸࡚㸪⾑୰ P4 ⃰ᗘࢆ㧗ࡃࡍࡿ࡜ LH ࣃࣝࢫ㢖
ᗘࡣపୗࡍࡿ୍᪉࡛㸪⾑୰ P4 ⃰ᗘࢆపࡃ⥔ᣢࡍࡿ࡜ LH ࣃࣝࢫ㢖ᗘࡣୖ᪼ࡍࡿࡇ࡜ࡀ▱
ࡽࢀ࡚࠸ࡿ㸦15㸪52㸧
ࠋࡲࡓ㸪Adams et al.㸦5㸧ࡣ㸪⮬↛Ⓨ᝟ᚋࡢ᤼༸☜ㄆ᫬࡟⭐ෆ␃⨨
ᆺ P4 〇๣ࢆᤄධࡋ㸪ࡑࡢᚋࡢ༸ᕢෆ࡛Ⓨ⫱ࡍࡿ➨ 1 ༸⬊Ἴࡢ༸⬊Ⓨ⫱ືែࢆほᐹࡋࡓ࡜
26
ࡇࢁ㸪ᤄධࡋ࡞࠿ࡗࡓ∵࡟ẚ࡭୺ᖍ༸⬊ࡢ᭱኱࡟㐩ࡋࡓᖹᆒ┤ᚄࡀᑠࡉ࠸ࡇ࡜ࢆሗ࿌ࡋ
࡚࠸ࡿࠋ༸⬊Ἴࡢ୰࡛༸⬊ࡀ୺ᖍ༸⬊࡜ࡋ࡚㑅ᢤࡉࢀ㸪ࡑࡢᚋⓎ⫱ࢆ⥅⥆ࡍࡿࡓࡵ࡟ࡣ㸪
㢛⢏ᒙ⣽⬊࡛ LHr ࡢⓎ⌧ࡀᚲ㡲࡛࠶ࡿ㸦13㸧
ࠋヨ㦂 1 ࡛ࡳࡽࢀࡓ㸪W1DF ࡢ W2DF ࡟ẚ
࡭࡚ᖹᆒ┤ᚄࡀ኱ࡁࡃ᥎⛣ࡋࡓࡇ࡜࠿ࡽ㸪W1DF ࡢⓎ⫱ᮇ㛫୰ࡢప࠸⾑୰ P4 ⃰ᗘ᥎⛣࡟
㉳ᅉࡍࡿ㧗࠸ LH ࣃࣝࢫ㢖ᗘ࡟ࡼࡾ୺ᖍ༸⬊ࡢⓎ⫱ࡀಁࡉࢀࡓ࡜᥎ ࡉࢀࡿࠋࡉࡽ࡟㸪
ヨ㦂 1 ࡛ࡣ Day 6 ࡟༸⬊ቨ⾑ὶࢆほᐹࡋࡓ࡜ࡇࢁ㸪W1DF ࡣ W2DF ࡟ẚ㍑ࡋ࡚㧗࠸ഴྥ
ࢆ♧ࡋࡓࠋ༸⬊ࡢⓎ⫱㐣⛬࡟࠾࠸࡚㸪༸⬊ቨ࡛ࡢ⾑⟶ᙧᡂࡣ㔜せ࡛࠶ࡿࡇ࡜ࡀ▱ࡽࢀ࡚
࠸ࡿ㸦95㸧
ࠋ㐣ཤࡢ◊✲࡟࠾࠸࡚㸪㑅ᢤᚋࡢ୺ᖍ༸⬊࡛ࡢ༸⬊ቨ⾑ὶࡀቑຍࡍࡿࡇ࡜ࡀሗ
࿌ࡉࢀ࡚࠸ࡿ㸦42㸧
ࠋࡲࡓ㸪㛢㙐๓ᚋࡢ༸⬊ቨ⾑ὶࢆẚ㍑ࡍࡿ࡜㛢㙐ᚋ࡟༸⬊ቨ⾑ὶࡀほ
ᐹࡉࢀ࡞ࡃ࡞ࡿ࡜࠸࠺ሗ࿌ࡶ࠶ࡿ㸦2㸧
ࠋࡇࢀࡽࡢࡇ࡜࠿ࡽ㸪࣮࢝ࣛࢻࣉࣛࢆ⏝࠸ࡓ༸⬊
ቨ⾑ὶࡢホ౯ࡣ༸⬊ࡢάຊࡸᶵ⬟ࢆホ౯ࡍࡿࡢ࡟᭷ຠ࡞ᣦᶆ࡜࡞ࡿ࡜⪃࠼ࡽࢀ㸪ᮏ◊✲
࡛ࡳࡽࢀࡓW1DF࡜W2DF ࡟࠾ࡅࡿ༸⬊ቨ⾑ὶࡢ㐪࠸ࡣ༸⬊ࡢᶵ⬟ࡢᕪࢆ♧ࡋ࡚࠸ࡿ࡜
⪃࠼ࡽࢀࡿࠋ ᮏ◊✲ࡢ⤖ᯝ࡟࠾࠸࡚㸪W1DF ࡛ࡣ W2DF ࡟ẚ࡭Ⓨ⫱⋡㸪ᖹᆒ┤ᚄ࠾ࡼ
ࡧ༸⬊ቨ⾑ὶࡀ㧗࠿ࡗࡓࡇ࡜࠿ࡽ㸪ᶵ⬟ᛶࡀ㧗࠸༸⬊࡛࠶ࡿࡇ࡜ࡀ᥎ ࡉࢀࡓࠋ
ヨ㦂 2 ࡛ࡣ PGF2α ࠾ࡼࡧ GnRH ࢆ⏝࠸࡚㸪㯤య㏥⾜ㄏ㉳ᚋࡢ༸⬊ࡢᡂ⇍࠾ࡼࡧ᤼༸࡟
⮳ࡿ㐣⛬ࡢ W1DF ࡜ W2DF ࡢᛶ㉁ࢆㄪ࡭㸪ẚ㍑ࡋࡓࠋ୺ᖍ༸⬊ࡢᖹᆒ┤ᚄࡣ Day 6 ࠿ࡽ
Day 9 ࡟࠿ࡅ࡚ᮇ㛫ࢆ㏻ࡋ࡚ W1DF ࡛኱ࡁࡃ᥎⛣ࡋࡓࠋ༸⬊ቨ⾑ὶࡢኚ໬ࢆẚ㍑ࡋࡓ࡜
ࡇࢁ㸪W1DF ࡟࠾࠸࡚ GnRH ᢞ୚๓ᚋ࡛᭷ព࡞ቑຍࡀほᐹࡉࢀࡓࡀ㸪W2DF ࡟࠾࠸࡚ࡣ
᭷ព࡞ቑຍࡣほᐹࡉࢀࡎ㸪Day 9 ࡟࠾࠸࡚ W1DF ࡛༸⬊ቨ⾑ὶࡀ W2DF ࡟ẚ࡭᭷ព࡟኱
ࡁ࠿ࡗࡓࠋ
࢘ࢩ࡛ࡣ LH ࢧ࣮ࢪ࠿ࡽ࠾ࡼࡑ 27 ᫬㛫ᚋ࡟᤼༸ࡍࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿ
㸦24㸧
ࠋ
ࡲࡓ࢘ࢩ࡛ࡣ㸪᤼༸┤๓㸦LH ࢧ࣮ࢪ᭚㟢࠾ࡼࡑ 19㹼21 ᫬㛫ᚋ㸧ࡢ༸⬊ቨ⾑ὶࡀቑຍࡍ
ࡿࡇ࡜ࡀሗ࿌ࡉࢀ࡚࠸ࡿ 㸦85㸧
ࠋ༸⬊ࡀ LH ࢧ࣮ࢪ࡟᭚㟢ࡉࢀࡿ࡜㸪༸⬊ෆ࡛ PG 㢮㸪
ࣄࢫࢱ࣑ࣥ㸪ࢥࣛࢤࢼ࣮ࢮ㸪࢟ࢽࣥ࠾ࡼࡧࣉࣛࢫ࣑ࣀ࣮ࢤࣥ࢔ࢡࢳ࣮࣋ࢱ࡞࡝ࡢ⏘⏕ࡀ
27
ஹ㐍ࡋ༸⬊⾑⟶⥙࡛ࡢ㏱㐣ᛶஹ㐍ࡸ༸⬊ቨࡢ⼥ゎ㸪⳼ⷧ໬ࡀ㉳ࡇࡿࡇ࡜࡛᤼༸ࡀ㐍⾜ࡋ㸪
ࡑࡢ཯ᛂࡣ⅖⑕⌧㇟࡟㢮ఝࡋ࡚࠸ࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿ㸦25㸧
ࠋࡑࡢࡓࡵ㸪LH ࢧ࣮ࢪ᭚
㟢ᚋ࡟ቑຍࡍࡿ༸⬊ቨ⾑ὶࡣ㸪ࡇࢀࡽࡢ⅖⑕ᛶኚ໬࡟㉳ᅉࡍࡿ⾑⟶ᶵ⬟ࡢኚ໬࡟ࡼࡿ࡜
⪃࠼ࡽࢀࡿࠋࡋ࠿ࡋ࡞ࡀࡽ㸪ᮏヨ㦂࡛ࡣ GnRH ᢞ୚ 24 ᫬㛫ᚋ࡟࠾ࡅࡿ༸⬊ቨ⾑ὶࡢ᭷
ព࡞ቑຍࡣ W1DF ࡢࡳ࡛ࡋ࠿ほᐹࡉࢀ࡞࠿ࡗࡓࠋࡲࡓ㸪BF㸣࡟࠾࠸࡚ࡶ Day 9 ࡟࠾࠸࡚
W1DF ࡛㧗࠸ࡇ࡜࠿ࡽ㸪W1DF ࡢ⾑ὶࡢቑຍ࠾ࡼࡧ㧗್ࡢཎᅉ࡜ࡋ࡚㸪༸⬊ቨෆ࡛ࡢ⾑
⟶ࡢศᕸࡀࡼࡾᗈ⠊ᅖ࡛࠶ࡿྍ⬟ᛶࡀ⪃࠼ࡽࢀࡿࠋࡲࡓ㸪LH ࢧ࣮ࢪ࡟ᑐࡍࡿ཯ᛂᛶࡀ
㧗࠸ࡇ࡜࡛༸⬊ቨ࡛ࡢ⅖⑕ᛶኚ໬ࡀࡼࡾ኱ࡁࡃ࡞ࡾ㸪⾑⟶࡬ࡢ⾑ᾮ㑏ὶ㔞ࡀቑຍࡋ࡚࠸
ࡿྍ⬟ᛶࡀ⪃࠼ࡽࢀࡿࠋᮍ⤒⏘∵ࢆ⏝࠸࡚Ⓨ᝟ㄏ㉳ࢆ⾜࡞ࡗࡓヨ㦂࡟࠾࠸࡚㸪GnRH ᢞ
୚ 26 ᫬㛫ᚋࡢ༸⬊ቨ⾑ὶ࡜ࡑࡢ᫬࡟ᐇ᪋ࡋࡓேᕤᤵ⢭ᚋࡢཷ⫾ࡢ᭷↓ࢆẚ㍑ࡋࡓ࡜ࡇ
ࢁ㸪ዷፎࡋࡓ∵࡛༸⬊ቨ⾑ὶࡀ᭷ព࡟㧗࠸ࡇ࡜ࢆሗ࿌ࡋ࡚࠸ࡿ㸦84㸧
ࠋࡇࡢ⌧㇟ࡣ㸪࣐࢘
ࢆ⏝࠸ࡓヨ㦂࡟࠾࠸࡚ࡶྠᵝࡢ⤖ᯝࡀᚓࡽࢀ࡚࠸ࡿ㸦87㸧
ࠋࡲࡓ㸪Ⓨ᝟ࢆㄏ㉳ࡋ GnRH
ᢞ୚ 26 ᫬㛫ᚋࡢ᤼༸๓༸⬊࠿ࡽᅇ཰ࡋࡓ༸Ꮚ࡟ᑐࡋ࡚㸪యእཷ⢭ࢆ⾜࠸ࡑࡢᚋࡢ⬇Ⓨ⫱
ࢆẚ㍑ࡋࡓ◊✲࡛ࡣ㸪༸Ꮚᅇ཰᫬ࡢ᤼༸๓༸⬊ࡢ༸⬊ቨ⾑ὶࡀ኱ࡁ࠸ሙྜ㸪⬇Ⓨ⫱ࡀⰋ
ዲ࡛࠶ࡿࡇ࡜ࡶ᫂ࡽ࠿࡟ࡉࢀ࡚࠸ࡿ㸦86㸧
ࠋࡇࢀࡽࡢࡇ࡜࠿ࡽ㸪᤼༸๓༸⬊ࡢ༸⬊ቨ⾑ὶ
ࡣ㸪ࡑࡢ༸⬊ࡢάຊࡢ⛬ᗘࢆ♧ࡍࡇ࡜ࡀ࡛ࡁࡿ࡜⪃࠼ࡽࢀࡿࠋࡲࡓ㸪ᮏ◊✲࠿ࡽ㸪GnRH
ᢞ୚᫬ࡢ Day 8 ࡟࠾ࡅࡿ⾑୰ E2 ⃰ᗘࡣ W1DF ࡛㧗࠸ࡇ࡜ࡀ♧ࡉࢀࡓࠋ㐣ཤࡢᐃ᫬ேᕤᤵ
⢭ࢆ⏝࠸ࡓヨ㦂࡟࠾࠸࡚㸪GnRH ᢞ୚᫬ࡢ⾑୰ E2 ⃰ᗘ࡜ࡑࡢᚋࡢཷ⫾ྍ⬟ᛶ࡜ࡢ㛫࡟ࡣ
ṇࡢ┦㛵㛵ಀࡀᏑᅾࡍࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿ㸦14㸧
ࠋࡲࡓ㸪ᐃ᫬ேᕤᤵ⢭᫬࡟Ⓨ᝟ᚩೃࢆ
♧ࡋ࡚࠸ࡓ࢘ࢩࡣ㸪Ⓨ᝟ᚩೃࢆ♧ࡋ࡚࠸࡞࠿ࡗࡓ࢘ࢩ࡟ẚ㍑ࡋ࡚ཷ⫾⋡ࡀ㧗࠸ࡇ࡜ࡀሗ
࿌㸦70㸧ࡉࢀ࡚࠾ࡾ㸪᤼༸๓ࡢ⾑୰ E2 ⃰ᗘࡣཷ⫾ᛶࡸ༸⬊ࡢάຊࢆ♧ࡍᣦᶆ࡜࡞ࡿࠋࡇ
ࢀࡽࡢࡇ࡜࠿ࡽ㸪
W1DFࡣ༸⬊ቨ⾑ὶࡀ኱ࡁࡃ㸪
᤼༸┤๓ࡢ⾑୰E2 ⃰ᗘࡀ㧗࠸ࡇ࡜࠿ࡽ㸪
W2DF ࡟ẚ࡭άຊࡀ㧗࠸ࡇ࡜ࡀ᥎ ࡉࢀࡿࠋ
28
ヨ㦂 3 ࡛ࡣ㸪ヨ㦂 2 ࡛ᚓࡽࢀࡓ㸪W1DF ࡢᛶ㉁ࢆࡉࡽ࡟ヲ⣽࡟ẚ㍑ࡍࡿࡓࡵ㸪LH ࢧ
࣮ࢪ᭚㟢๓ᚋࡢ༸⬊ᾮᛶࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥࡸ㢛⢏ᒙ⣽⬊࡛Ⓨ⌧ࡋ࡚࠸ࡿ mRNA Ⓨ⌧
㔞ࢆẚ㍑ࡋࡓࠋ
LH ࢧ࣮ࢪ᭚㟢๓ࡢᡂ⇍༸⬊ෆ࡛㸪ࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥྜᡂ㐣⛬ࡣ㸪༸⬊ቨࡢෆ༸⬊
⭷⣽⬊࡟࠾࠸࡚㸪ࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥࡢᇶ㉁࡜࡞ࡿࢥࣞࢫࢸ࣮ࣟࣝࡀ⣽⬊ෆ࡟ྲྀࡾ㎸ࡲ
ࢀࡿࡇ࡜࠿ࡽጞࡲࡾ㸪ࡇࡢࢥࣞࢫࢸ࣮ࣟࣝࡣ StAR ࡟ࡼࡾ࣑ࢺࢥࣥࢻࣜ࢔ෆ࡟ྲྀࡾ㎸ࡲ
ࢀ㸪⥆࠸࡚࣑ࢺࢥࣥࢻࣜ࢔ෆ⭷ୖ࡟Ꮡᅾࡍࡿ P450-scc ࡟ࡼࡾࢥࣞࢫࢸ࣮ࣟࣝ࠿ࡽࣉࣞࢢ
ࢿࣀࣟࣥ࡟ኚ᥮ࡉࢀ㸪ࡑࡢᚋ⁥㠃ᑠ⬊యୖ࡟Ꮡᅾࡋ࡚࠸ࡿ 3β-HSD ࡟ࡼࡾࣉࣞࢢࢿࣀࣟ
ࣥ࠿ࡽ P4 ࡬࡜ኚ᥮ࡉࢀࡿ㸦22㸧
ࠋP4 ࡣ C17 Ỉ㓟໬㓝⣲άᛶ࡟ࡼࡾ 17α̺ࣄࢻࣟ࢟ࢩࣉࣟ
ࢪ࢙ࢫࢸࣟࣥ࡬࡜ኚ᥮ࡉࢀ㸪C17-20 ഃ㙐ษ᩿㓝⣲άᛶ࡟ࡼࡾ A4 ࡟ኚ᥮ࡉࢀࡿ㸦31㸪59㸧
ࠋ
ࡉࡽ࡟ A4 ࡣ༸⬊⭷⣽⬊࠿ࡽ㢛⢏ᒙ⣽⬊࡟⛣⾜ࡋࡑࡇ࡛࢔࣐ࣟࢱ࣮ࢮ㸦CYP19A1㸧࡟ࡼ
ࡾ E2 ࡟ኚ᥮ࡉࢀࡿ㸦12㸧ࡇ࡜࡛༸⬊ෆ࡛ࢫࢸࣟ࢖ࢻࡀ⏘⏕ࡉࢀ࡚࠸ࡿࠋᮏヨ㦂࡟࠾࠸࡚㸪
༸⬊ᾮ୰ E2 ࠾ࡼࡧ A4 ⃰ᗘࡣ W1DF ࡛㧗࠿ࡗࡓࡀ㸪CYP19A1 mRNA Ⓨ⌧㔞࡟࠾࠸࡚ࡣ
୧⩌࡟ᕪࡣ࡞࠿ࡗࡓࠋ㐣ཤ࡟⾜ࢃࢀࡓ◊✲࡟࠾࠸࡚㸪༸⬊ෆ࡛ࡢ E2 ⏘⏕ࡢไ㝈せᅉࡣ㸪
࢔࣐ࣟࢱ࣮ࢮάᛶ࡛ࡣ࡞ࡃ㸪ෆ༸⬊⭷࡛⏘⏕ࡉࢀࡿ A4 ࡟ࡼࡿ࡜ࡇࢁࡀ኱ࡁ࠸࡜࠸࠺ሗ࿌
ࡀ࠶ࡿ㸦9㸧
ࠋࡇࢀࡽࡢࡇ࡜࠿ࡽ㸪W1DF ࡟࠾ࡅࡿ༸⬊ᾮ E2 ⃰ᗘࡢ㧗್ࡣ W1DF ࡢෆ༸
⬊⭷࡛ࡢ㧗࠸ A4 ⏘⏕⬟࡟ࡼࡿࡶࡢ࡛࠶ࡿ࡜᥎ ࡉࢀࡿࠋLH ࢧ࣮ࢪ᭚㟢๓ࡢ㢛⢏ᒙ⣽⬊
࡛Ⓨ⌧ࡋ࡚࠸ࡿ LHr mRNA Ⓨ⌧㔞ࢆẚ㍑ࡍࡿ࡜㸪W1DF ࡀ㧗࠸ࡇ࡜ࡀ♧ࡉࢀࡓࠋ࢘ࢩࡢ
㢛⢏ᒙ⣽⬊࡟࠾࠸࡚㸪LH ࡣ LHr mRNA Ⓨ⌧㔞ࢆቑຍࡉࡏࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠾ࡾ㸦56㸧
㸪
ヨ㦂 1 ࡟࠾࠸࡚ W1DF Ⓨ⫱ᮇ㛫୰ࡢ⾑୰ P4 ⃰ᗘࡀప࠿ࡗࡓࡇ࡜࠿ࡽ㸪
W1DF Ⓨ⫱ᮇ㛫୰
ࡢ㧗࠸LHࣃࣝࢫ㢖ᗘࡀW1DF㢛⢏ᒙ⣽⬊୰࡟࠾ࡅࡿLHrⓎ⌧㔞ࢆ㧗ࡵࡓ࡜⪃࠼ࡽࢀࡿࠋ
༸⬊ࡀ LH ࢧ࣮ࢪ࡟཯ᛂࡋ࡚᤼༸࡛ࡁࡿࡼ࠺࡟࡞ࡿࡓࡵ࡟ࡣ㸪㢛⢏ᒙ⣽⬊࡟࠾ࡅࡿ LHr
Ⓨ⌧ࡀᚲ㡲࡛࠶ࡿࡇ࡜࠿ࡽ㸪W1DF ࡢ㢛⢏ᒙ⣽⬊ࡣ LH ࢧ࣮ࢪࢆཷࡅ࡚᤼༸࡬ྥ࠿࠺཯
29
ᛂᛶࡀࡼࡾ㧗࠸ࡇ࡜ࡀ᥎ ࡉࢀ㸪ヨ㦂 2 ࡟࠾ࡅࡿ Day 9 ࡛ࡢ W1DF ࡢ༸⬊ቨ⾑ὶࡢ㧗್
ࡣ㸪W1DF ࡢ LH ࢧ࣮ࢪ࡟ᑐࡍࡿ᤼༸๓ࡢ༸⬊ቨ⾑ὶቑຍ࡟࠾ࡅࡿ཯ᛂᛶࡢ㧗ࡉࢆ཯ᫎ
ࡋ࡚࠸ࡿྍ⬟ᛶࡀ♧၀ࡉࢀࡿࠋ
༸⬊ࡀ LH ࢧ࣮ࢪ࡟᭚㟢ࡉࢀࡿ࡜㸪༸⬊ࢆᵓᡂࡍࡿ⣽⬊࡛࠶ࡿ㢛⢏ᒙ⣽⬊ࡸ༸⬊⭷⣽
⬊ࡣ㯤య⣽⬊࡬࡜ኚ໬ࡍࡿࡇ࡜࡛㸪ࢫࢸࣟ࢖ࢻྜᡂࡣ E2 ྜᡂ࠿ࡽ P4 ྜᡂ࡬࡜ᛴ㏿࡟⛣
⾜ࡋ࡚࠸ࡃ㸦89㸧
ࠋࡲࡓ㸪LH ࢧ࣮ࢪ᭚㟢ᚋࡢ༸⬊ᾮ୰࡟࠾࠸࡚㸪PG 㢮ࡢ⃰ᗘࡀᛴ⃭࡟
ୖ᪼ࡋ࡚࠸ࡃ㸦1㸪3㸧
ࠋPG ࡣᒁᡤ࡟࠾ࡅࡿ⾑⟶సືᛶస⏝㸦21㸪98㸧ࡸ⾑⟶㏱㐣ᛶస⏝
㸦26㸧ࢆᣢࡘࡇ࡜ࡀ▱ࡽࢀ࡚࠾ࡾ㸪᤼༸┤๓ࡢ༸⬊య✚ቑຍ㸦61㸧࡜ࡑࡢᚋࡢ༸⬊◚⿣
㸦26㸧࡟㛵ࢃࡿ࡜ࡉࢀ࡚࠸ࡿࠋࡉࡽ࡟㸪᤼༸┤๓࡟࠾ࡅࡿ PGE2 ྜᡂࢆᢚไࡍࡿ࡜㸪༸
⬊ࡢ◚⿣ࢆᢚไࡍࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿ㸦71㸧
ࠋ࢘ࢩ࡟࠾࠸࡚㏥⾜㛤ጞ᫬ࡢ㯤య࡟࠾ࡅࡿ
⾑ὶࡢቑຍ࡟ࡣ⾑⟶ᣑᙇᅉᏊ࡛࠶ࡿ୍㓟໬❅⣲㸦NO㸧ࡀ㛵୚ࡍࡿࡇ࡜ࡀሗ࿌ࡉࢀ࡚࠾ࡾ
㸦83㸧
㸪࣐࢘ࢫ࡟࠾࠸࡚༸⬊ෆ࡛ࡶⓎ⌧ࡀ☜ㄆࡉࢀ࡚࠸ࡿ㸦104㸧
ࠋVEGF ࡸ FGF ࡣ༸⬊
Ⓨ⫱㸦82㸧ࡸ㯤యᙧᡂ㸦105㸧࡟࠾ࡅࡿ⾑⟶᪂⏕࡟㔜せ࡞ᙺ๭ࢆᯝࡓࡍࡇ࡜ࡀ▱ࡽࢀ࡚࠾
ࡾ㸪ࡇࢀࡽࡢᅉᏊࡢⓎ⌧㔞ࢆẚ㍑ࡍࡿࡇ࡜࡛ LH ࢧ࣮ࢪ๓ᚋ࡟᤼༸࡟⮳ࡿ㐣⛬࡟࠾ࡅࡿ
༸⬊ᶵ⬟ࢆホ౯࡛ࡁࡿ࡜⪃࠼ࡓࠋ
ᮏヨ㦂࡛ࡣ㸪COX-2㸪PGES ࠾ࡼࡧ PGFS mRNA Ⓨ⌧㔞࡟᭷ព࡞ᕪࡀ࡞࠿ࡗࡓࡇ࡜࠿
ࡽ㸪᤼༸㐣⛬࡟ᚲ㡲࡞ࡇࢀࡽࡢᅉᏊࡢⓎ⌧㔞࡟ཬࡰࡍ㸪LH ࢧ࣮ࢪ࡟ᑐࡍࡿ཯ᛂᛶࡀ
W1DF ࡜ W2DF ࡜ࡢ㛫࡛ᕪ␗ࡣ࡞࠸ࡇ࡜ࢆ♧၀ࡋ࡚࠸ࡿ࡜⪃࠼ࡽࢀࡿࠋࡘࡲࡾ㸪ࡇࢀࡽ
ࡢᅉᏊࡢⓎ⌧㔞ࡢ㐪࠸ࡀ㸪༸⬊ቨ⾑ὶࡢᕪ␗ࢆࡶࡓࡽࡋࡓཎᅉ࡛࠶ࡿ࡜ࡣ⪃࠼ࡽࢀ࡞࠸ࠋ
୍᪉࡛㸪eNOS mRNA Ⓨ⌧㔞ࡣ W1DF ࡛㧗࠸ഴྥࢆ♧ࡋࡓࡇ࡜࠿ࡽ㸪༸⬊ࡢ⾑⟶ᣑᙇస
⏝࡟ W1DF ࡜ W2DF 㛫࡛ᕪࡀ⏕ࡌ࡚࠸ࡿྍ⬟ᛶࡶ⪃࠼ࡽࢀࡿࠋࡋ࠿ࡋ࡞ࡀࡽ㸪༸⬊ቨࡢ
⾑⟶⥙ࡣෆ༸⬊⭷࡟ศᕸࡋ࡚࠾ࡾ㸪㢛⢏ᒙ⣽⬊࡟ࡣ⾑⟶ࡀ౵ධࡋ࡚࠸࡞࠸㸦29㸧ࡇ࡜࠿
ࡽ㸪ෆ༸⬊⭷࡛ࡢ⾑⟶⥙ࡢศᕸࡸෆ༸⬊⭷⣽⬊࡛ࡢ iNOS ࠾ࡼࡧ eNOS ࡞࡝ࡢ⾑⟶సື
30
ᛶᅉᏊࡢⓎ⌧㔞ࢆẚ㍑ࡍࡿࡇ࡜࡛㸪༸⬊ቨ⾑ὶࡢᕪ␗ࢆࡶࡓࡽࡋࡓཎᅉ࡟ࡘ࠸࡚㏣ཬࡋ
࡚࠸ࡃᚲせࡀ࠶ࡿ࡜⪃࠼ࡿࠋ
P4 ⏘⏕࡟㛵ࢃࡿࢫࢸࣟ࢖ࢻྜᡂ㓝⣲࡛࠶ࡿ StAR㸪P450-scc ࠾ࡼࡧ 3β-HSD mRNA Ⓨ⌧
㔞ࢆ W1DF ࡜ W2DF 㛫࡛ẚ㍑ࡋࡓ࡜ࡇࢁ㸪P450-scc ࠾ࡼࡧ 3β-HSD mRNA ࡀ W1DF ࡛
㧗ࡃⓎ⌧ࡋ࡚࠸ࡓࠋࡲࡓ㸪⾑⟶ᙧᡂᅉᏊ࡛࠶ࡿ VEGF120㸪164 ࠾ࡼࡧ FGF-2 mRNA Ⓨ⌧
㔞࡟࠾࠸࡚ࡶ㸪VEGF164 mRNA Ⓨ⌧㔞ࡀ W1DF ࡛㧗ࡃⓎ⌧ࡋ࡚࠸ࡓࠋ㢛⢏ᒙ⣽⬊࡟ᑐ
ࡋ࡚㸪LH ࡣ VEGF㸦45㸧࠾ࡼࡧ P450-scc 㸦106㸧ࡢⓎ⌧ࢆୖ᪼ࡉࡏࡿ࡜ሗ࿌ࡉࢀ࡚࠾ࡾ㸪
W1DF ࡢ LH ࢧ࣮ࢪ᭚㟢๓ࡢ㢛⢏ᒙ⣽⬊࡛ LHr mRNA ࡢⓎ⌧ࡀ㧗࠿ࡗࡓࡇ࡜࠿ࡽ㸪ࡇࢀ
ࡽࡢᅉᏊࡢⓎ⌧㔞ࡀୖ᪼ࡋࡓ࡜᥎ ࡉࢀࡿࠋࡇࡢࡼ࠺࡟ࢫࢸࣟ࢖ࢻྜᡂ㓝⣲࠾ࡼࡧ⾑⟶
᪂⏕ᅉᏊࡢⓎ⌧ࡀ W1DF ࡛㧗ࡃ࡞ࡗ࡚࠸ࡓࡇ࡜࠿ࡽ㸪᤼༸ᚋ࡟ᙧᡂࡉࢀࡿ㯤యࡢᙧែࡸ
ᶵ⬟ࡀ W1CL ࡟࠾࠸࡚㧗࠸ࡇ࡜ࡀ᥎ ࡉࢀࡓࠋ
ヨ㦂 4 ࡟࠾࠸࡚㸪W1DF ᤼༸ᚋ࡟ᙧᡂࡉࢀࡿ W1CL ࡢ㯤య᩿㠃✚㸪㯤య⾑ὶ㠃✚࠾ࡼ
ࡧ⾑୰ P4 ⃰ᗘࡣ㧗࠿ࡗࡓࠋࡇࢀࡲ࡛㸪᤼༸๓༸⬊࡟ VEGF ࡢ࢔ࣥࢱࢦࢽࢫࢺࢆᢞ୚ࡋࡓ
ሙྜ㸪ࡑࡢᚋ࡟ᙧᡂࡉࢀࡿ㯤యࡢᙧែࡸᶵ⬟ࢆపୗࡉࡏࡿࡇ࡜ࡀሗ࿌ࡉࢀ࡚࠸ࡿ㸦46㸧
ࠋ
ࡲࡓ㸪FGFR1 ࡟ᑐࡍࡿ࢖ࣥࣄࣅࢱ࣮ࢆᇵ㣴ࡋࡓ㯤య⣽⬊࡟ῧຍࡍࡿ࡜⾑⟶ෆ⓶⣽⬊ࡢࢿ
ࢵࢺ࣮࣡ࢡࡸ⾑⟶ഃᯞࢆⴭࡋࡃῶᑡࡉࡏࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿ㸦101㸧
ࠋࡇࢀࡽࡢࡇ࡜࠿
ࡽ㸪W1DF ࡟࠾ࡅࡿ⾑⟶ᙧᡂᅉᏊࡢ㧗࠸Ⓨ⌧࡟ࡼࡾ㸪㯤యᙧᡂึᮇࡢ⾑⟶ᙧᡂࡢ⛬ᗘࡀ
W1CL ࡛኱ࡁࡃ࡞ࡗࡓ࡜⪃࠼ࡽࢀࡿࠋࡇࢀࡲ࡛㸪᤼༸๓༸⬊ࡢ┤ᚄࡀ኱ࡁ࠸ሙྜ㸪ࡑࡢ
ᚋ࡟ᙧᡂࡉࢀࡿ㯤యࡢ┤ᚄࡶ኱ࡁࡃ࡞ࡿ࡜࠸࠺ሗ࿌ࡀ࠶ࡿ㸦97㸧
ࠋᮏヨ㦂࡟࠾࠸࡚ࡶ᤼༸
๓༸⬊ࡣ W1DF ࡛኱ࡁࡃ㸪ࡑࡢᚋࡢ㯤య᩿㠃✚ࡀ኱ࡁ࠸ࡇ࡜࠿ࡽ㸪㐣ཤࡢሗ࿌࡜୍⮴ࡍ
ࡿࠋࡉࡽ࡟㸪W1CL ࡛ࡣ㯤యᙧᡂึᮇ࡛ࡢ⾑⟶ᙧᡂࡢ⛬ᗘࡀ኱ࡁ࠿ࡗࡓࡇ࡜࠿ࡽ㸪⾑ᾮ
㑏ὶ㔞ࡀቑຍࡋ㸪㯤యࡢⓎ⫱ࡀࡉࡽ࡟ಁࡉࢀ࡚኱ࡁࡃⓎ⫱ࡋࡓ࡜⪃࠼ࡽࢀࡿࠋ㐣ཤࡢሗ
࿌࡟࠾࠸࡚㸪㯤యࡢ┤ᚄ࡜⾑୰ P4 ⃰ᗘ࡟ࡣṇࡢ┦㛵㛵ಀࡀᏑᅾࡍࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿ
31
㸦58㸧
ࠋᮏヨ㦂࡟࠾࠸࡚ࡶ㸪⾑୰ P4 ⃰ᗘࡀ㧗ࡃ᥎⛣ࡋࡓཎᅉ࡟㸪W1CL ࡢࢧ࢖ࢬࡀ኱ࡁ
࠸ࡇ࡜ࡶ⪃࠼ࡽࢀࡿࡀ㸪㯤యᙧᡂึᮇ࡟⾑ὶ㔞ࡀከ࠸ࡇ࡜࡛㯤య⣽⬊࡛ࡢ P4 ⏘⏕ࡢஹ㐍
ࡸ㸪⏘⏕ࡉࢀࡓ P4 ࢆࡼࡾຠ⋡Ⰻࡃ඲㌟ᚠ⎔࡟ᨺฟ࡛ࡁࡓࡇ࡜ࡀ㧗࠸⾑୰ P4 ⃰ᗘࢆࡶࡓ
ࡽࡋࡓࡢ࡛ࡣ࡞࠸࠿࡜᥎ ࡉࢀࡿࠋࡲࡓ㸪ヨ㦂 3 ࠿ࡽ P4 ྜᡂ㓝⣲ࡢ mRNA Ⓨ⌧㔞ࡀ㧗
࠿ࡗࡓࡇ࡜࠿ࡽ㸪㯤య⣽⬊࡛ࡢࢫࢸࣟ࢖ࢻྜᡂ⬟ࡢᶵ⬟ࡢ㧗࠸ࡇ࡜ࡶせᅉࡢ୍ࡘ࡟࡞ࡿ
࡜⪃࠼ࡽࢀࡿࠋࡇࢀࡽࡢࡇ࡜࠿ࡽ㸪W1DF ࡣ༸⬊ࡢᶵ⬟ࡔࡅ࡛࡞ࡃ㸪ࡑࡢᚋ࡟ᙧᡂࡉࢀ
ࡿ㯤యࡢάຊࡶ㧗࠸ࡇ࡜ࡀ♧ࡉࢀࡓࠋࡲࡓ㸪㯤యᶵ⬟ࡣ᤼༸┤๓ࡢ༸⬊ᶵ⬟࡟኱ࡁࡃᙳ
㡪ࢆཷࡅࡿࡇ࡜ࡀ♧၀ࡉࢀࡓࠋ
௨ୖࡢࡇ࡜࠿ࡽ㸪W1DF ࡢᛶ㉁ࢆ᫂ࡽ࠿࡟ࡍࡿ┠ⓗ࡛ W2DF ࡜༸⬊Ⓨ⫱ືែ㸪᤼༸࡟
⮳ࡿࡲ࡛ࡢ༸⬊ቨ⾑ὶࡸ⾑୰ E2 ⃰ᗘ㸪LH ࢧ࣮ࢪ᭚㟢๓ᚋ࡟࠾ࡅࡿ༸⬊ᾮᛶࢫࢸࣟ࢖ࢻ
⃰ᗘ㸪㢛⢏ᒙ⣽⬊࡛Ⓨ⌧ࡋ࡚࠸ࡿ LHr㸪ࢫࢸࣟ࢖ࢻྜᡂ㓝⣲㸪⾑⟶సືᛶᅉᏊ࠾ࡼࡧ⾑
⟶ᙧᡂᅉᏊࡢ mRNA Ⓨ⌧㔞㸪ࡉࡽ࡟ࡣ᤼༸ᚋ࡟ᙧᡂࡉࢀࡿ㯤యࡢᙧែ࠾ࡼࡧᶵ⬟ࢆẚ㍑
ࡋࡓ࡜ࡇࢁ㸪W1DF ࡣࢧ࢖ࢬࡸᶵ⬟ᛶࡀ㧗ࡃ㸪άຊࡢ㧗࠸༸⬊࡛࠶ࡿࡇ࡜ࡀ᫂ࡽ࠿࡟࡞
ࡗࡓࠋ
2㸫8㸬ᑠᣓ
㯤యᙧᡂᮇ࡟Ⓨ⫱ࡍࡿW1DFࡣ㸪㯤య㛤ⰼᮇ࡟Ⓨ⫱ࡍࡿW2DF࡟ẚ࡭༸⬊ࡢⓎ⫱㸪༸⬊
ቨ⾑ὶ㸪᤼༸๓༸⬊ࡢ㢛⢏ᒙ⣽⬊࡛Ⓨ⌧ࡋ࡚࠸ࡿLHr㸪⾑⟶᪂⏕ᅉᏊ࠾ࡼࡧࢫࢸࣟ࢖ࢻྜ
ᡂ㓝⣲ࡢmRNAⓎ⌧㔞㸪ࢫࢸࣟ࢖ࢻྜᡂ⬟㸪㯤యᙧᡂ࠾ࡼࡧ㯤యᶵ⬟ࡀ㧗ࡃ㸪άຊࡀ㧗࠸
ࡇ࡜ࡀ♧၀ࡉࢀࡓࠋࡇࢀࡽࡢW1DFࡢᛶ㉁ࡣ㸪W1DFⓎ⫱ᮇ㛫୰ࡢ⾑୰P4⃰ᗘࡢప࠸᥎⛣
࡟ࡼࡿࡶࡢ࡜᥎ ࡉࢀࡓࠋ
32
W1DF
Spontaneous
ovulation
Day0
B-mode US
Day1
Day2
Day3
Day4
Color Doppler US
Day5
Day6
W2DF
Spontaneous
ovulation
Day7
Induced ovulation
Day2
Day0
B-mode US
Day1
Day2
Day3
Day4
Color Doppler US
Day5
Day6
GnRH
Fig. 2.1.
Schematic diagram of experimental model of W1DF and W2DF in Experiment 1.
In the first follicular wave, the day of spontaneous ovulation was defined as Day
0. In the second follicular wave, the day of spontaneous ovulation was defined as
Day 7. Ovulation of the first-wave dominant follicle (DF) was induced by
GnRH treatment on Day 2 to induce a new follicular wave, and induced
ovulation was confirmed 36 h after GnRH treatment on Day 0. W1DF; DF in the
first follicular wave. W2DF;DF in the second follicular wave. B-mode US =
trans-rectal ultrasonography. Color Doppler US = trans-rectal color Doppler
ultrasonography.
33
(B)
(A)
Fig. 2.2.
Measuring method of blood flow area (BFA). Image of (A) is
dominant follicle with blood flow signals in the follicular wall
using color Doppler ultrasonography. The area of blood flow
signals which is enclosed by white line is measured as BFA
(image B).
34
Plasma
P4Pconcentration
of P4(ng/ml)
Plasma
(ng/ml)
4 concentration
8.0
7.0
W1DF
W2DF
6.0
5.0
4.0
3.0
G䠖P < 0.001
D䠖P < 0.001
G,D䠖NS
2.0
1.0
0
Day0 Day1 Day2 Day3 Day4 Day5 Day6
Days from follicular wave emergence
Fig. 2.3.
Comparative changes of plasma P4 concentration of W1DF and
W2DF from Day 0 to 6. Day 0 = The day of follicular wave
emergence. W1DF; Dominant follicle (DF) in the first follicular
wave. W2DF;DF in the second follicular wave. Effect of group
(G) (P < 0.001), day (D) (P < 0.001) and interaction between
group and day (G,D) (NS). Values are mean r SEM of each point.
35
Dominant follicle diameter (mm)
17
16
15
14
13
W1DF
W2DF
G䠖P < 0.01
D䠖P < 0.01
G,D䠖P < 0.01
12
11
10
9
8
Day3
Day4
Day5
Day6
Days from follicular wave emergence
Fig. 2.4.
Comparative changes of dominant follicle (DF) of W1DF and W2DF
from Day 3 to 6. Day 0 = The day of follicular wave emergence. W1DF;
DF in the first follicular wave. W2DF; DF in the second follicular wave.
Effect of group (G) (P < 0.01), day (D) (P < 0.01) and interaction
between group and day (G,D) (P < 0.01). The asterisk denotes
difference between each point, : P < 0.05. Values are mean r SEM of
each point.㻌
36
Table 2.1. Blood flow in the follicular wall on Day6.
W1DF
W2DF
P-value
BFA(cm2)
0.32㼼0.05
0.21㼼0.05
BF% (%)
24.37㼼2.64
18.35㼼3.17
P < 0.1
P < 0.1
Values are mean 㼼 SEM.
W1DF = Dominant follicle (DF) in the first follicular wave.
W2DF = DF in the second follicular wave.
BFA = Blood flow area.
BF% = The percentage of follicle circumference with blood flow signals.
37
W1DF
Spontaneous
ovulation
Color Doppler US
Day0
Day6
W2DF
PGF2D
Spontaneous
ovulation
Day7
Day7
Day8
Day9
GnRH
Induced ovulation
Day2
Day0
Color Doppler US
Day6
GnRH
PGF2D
Day7
Day8
Day9
GnRH
Fig. 2.5.
Schematic diagram of experimental model of W1DF and W2DF in Experiment 2.
In the first follicular wave, the day of spontaneous ovulation was defined as Day
0. To induce follicular maturation, PGF2α and GnRH were administrated on Day
6 and 8, respectively. In the second follicular wave, the day of spontaneous
ovulation was defined as Day 7. Ovulation of the first-wave dominant follicle
(DF) was induced by GnRH treatment on Day 2 to induce a new follicular wave,
and induced ovulation was confirmed 36 h after GnRH treatment on Day 0.
PGF2α and GnRH were administrated on Day 6 and 8, respectively. W1DF; DF in
the first follicular wave. W2DF;DF in the second follicular wave. Color Doppler
US = trans-rectal color Doppler ultrasonography.
38
Dominant follicle diameter (mm)
20
19
W1DF
W2DF
18
17
16
15
G : P < 0.001
D : P < 0.001
G,D : NS
14
13
12
Day6
Day8
Day9
Days from follicular wave emergence
Fig. 2.6.
Comparative changes of dominant follicle (DF) of W1DF and
W2DF from Day 6 to 9. Day 0 = The day of follicular wave
emergence. W1DF; DF in the first follicular wave. W2DF;DF in
the second follicular wave. Effect of group (G) (P < 0.001), day
(D) (P < 0.001) and interaction between group and day (G,D) (NS).
Values are mean r SEM of each point.
39
Plasma P4
P4 concentration
concentration (ng/ml)
(ng/ml)
8.0
W1DF
W1DF
7.0
W2DF
W2DF
6.0
5.0
G : P < 0.01
D : P < 0.01
G : P < 0.01
G,D : P < 0.05
D : P < 0.001
4.0
3.0
G,D : P < 0.05
䠆䠖P < 0.05
2.0
1.0
0
Day6 Day7
Day8 Day9
Days from follicular wave emergence
Fig. 2.7.
Comparative changes of plasma P4 concentration of W1DF and
W2DF from Day 6 to 9. Day 0 = The day of follicular wave
emergence. W1DF; Dominant follicle (DF) in the first follicular
wave. W2DF;DF in the second follicular wave.㻌 Effect of group
(G) (P < 0.01), day (D) (P < 0.01) and interaction between
group and day (G,D) (P < 0.05). The asterisk denotes difference
between each point, : P < 0.05. Values are mean r SEM of
each point.
40
BFA
1.2
BFA(cm2)
1.0
0.8
G : P < 0.01
D : P < 0.01
G,D : P < 0.05
0.6
0.4
0.2
Day6
BF%
Day8
70
Day9
W1DF
W2DF
BF% (%)
60
G : P < 0.01
D : P < 0.01
G,D : P < 0.01
50
40
30
20
10
Day6
Day8
Day9
Days from follicular wave emergence
Fig. 2.8.
Comparative changes of blood flow area (BFA) and the percentage of follicle
circumference with blood flow signals (BF%) of W1DF and W2DF on Day 6 to 9.
Cows were treated with PGF2α and GnRH on Day 6 and Day 8, respectively. Day
0 = day of follicular wave emergence. W1DF; Dominant follicle (DF) in the first
follicular wave. W2DF;DF in the second follicular wave. For BFA, effect of
group (G) (P < 0.01), day (D) (P < 0.01) and interaction between group and day
(G,D)(P < 0.05). For BF%, effect of group (G) (P < 0.01), day (D) (P < 0.01) and
interaction between group and day (G,D) (P < 0.01). The asterisk denotes
difference between each points, : P < 0.05, : P < 0.01. Values are mean r
SEM of each point.
41
Table 2.2. Plasma E2 concentration on Day 8.
E2 (pg/ml)
W1DF
W2DF
P-value
7.5㼼0.9
4.4㼼0.5
P < 0.01
Values are mean 㼼 SEM.
Day8 = The day of after 48h of PGF2α treatment.
W1DF = Dominant follicle (DF) in the first follicular wave.
W2DF = DF in the second follicular wave.
42
Follicle aspilation
W1DF
Spontaneous
ovulation
Follicle aspilation
Day0
Day6
Day7
Day8
Day9
Follicle aspilation
W2DF
PGF 2D
Spontaneous
ovulation
Day 7
GnRH
Follicle aspilation
Induced ovulation
Day 2
Day0
Day6
PGF2D
GnRH
Day7
Day8
Day9
GnRH
Fig. 2.9.
Schematic diagram of experimental model of W1DF and W2DF in
Experiment 3. In the first follicular wave, the day of spontaneous ovulation
was defined as Day 0. To induce follicular maturation, PGF2α and GnRH
were administrated on Day 6 and 8, respectively. In the second follicular
wave, the day of spontaneous ovulation was defined as Day 7. Ovulation of
the first-wave dominant follicle (DF) was induced by GnRH treatment on
Day 2 to induce a new follicular wave, and induced ovulation was
confirmed 36 h after GnRH treatment on Day 0. PGF2α and GnRH were
administrated on Day 6 and 8, respectively. W1DF; DF in the first follicular
wave. W2DF;DF in the second follicular wave. DF were aspirated by transvaginal ultrasonography in different estrous cycle.
43
Table 2.3. Primers used in real-time PCR.
Gene
Sequence of nucleotide(5䇻-3䇻)
Fa
Rb
Size(bp)
Annealing
Accesion No.
temperature( q C)
GCATCCACAAGCTTCCAGATGTTACGA
GGGAAATCAGCGTTGTCCCATTGA
204
62
CYP19A1 F
R
TTGCAAAGCATCCCCAGGTT
AGGTCCACAACGGGCTGGTA
151
60
Z32741
COX -2
F
R
TCCTGAAACCCACTCCCAACA
TGGGCAGTCATCAGGCACAG
241
60
AF031698
PGFS
F
R
GATCAAAGCGATTGCAGACA
CAATGCGTTCAGGTGTCACT
113
59
S54973
PGES
F
R
CGCTGCTGGTCATCAAAAT
GGAAGGGGTAGATGGTCTCC
186
60
AY032727
iNOS
F
R
TCATCTTCGCCACCAAGCAG
CAGTGATGGCCGACCTGATG
180
60
U14640
eNOS
F
R
GGAAATCGGGGGTCTGGAGT
TTGGCGAGCTGAAAGCTGTG
219
60
M89952
VEGF120 F
R
CCCAGATGAGATTGAGTTCATTTT
GCCTCGGCTTGTCACATTTT
377
56
M32976
VEGF164 F
R
CCCAGATGAGATTGAGTTCATTTT
AGCAAGGCCCACAGGGATTT
245
58
M32976
F
R
GTGCATTTTGCCAATCACCT
TTATTGAAAACGTGCCACCA
203
54.3
M174189
P450-scc
F
R
CTGCAAATGGTCCCACTTCT
CACCTGGTTGGGTCAAACTT
209
56.3
K02103
3β-HSD
F
R
TCCACACCAGCACCATAGAA
AAGGTGCCACCATTTTTCAG
118
56.3
X17614
F
R
CTCTCAAGGGCATTCTAGGC
TGACAAAGTGGTCGTTGAGG
160
60
LHr
StAR
GAPDH
a
b
F, forward
R, reverse
44
NM 174381
NM001034034
Table 2.4. Sex steroids concentration in follicular fluid on Day 8.
W1DF
P4 (ng/ml)
37.4㼼8.5
E2 (ng/ml)
1,942.4㼼247.9
A4 (ng/ml)
161.8㼼26.2
W2DF
P-value
34.6㼼2.2
NS
1,169.3㼼90.9
P < 0.05
104.6㼼12.7
P < 0.05
Values are mean 㼼 SEM.
Day 8 = The day of after 40h of PGF2α treatment.
W1DF = Dominant follicle (DF) in the first follicular wave.
W2DF = DF in the second follicular wave.
45
LHr
CYP19A1
*
4.0
0.3
/GAPDH
/GAPDH
3.0
0.2
0.1
0
2.0
1.0
0
W1DF
W2DF
W1DF
W2DF
Fig. 2.10.
The relative amounts of mRNA of LHr and CYP19A1 in W1DF and
W2DF granulosa cells on Day 8. In each figure, the black bar indicates
W1DF and the white bar indicates W2DF. W1DF; Dominant follicle (DF) in
the first follicular wave. W2DF;DF in the second follicular wave. Day 8 =
the day of after 40h of PGF2α treatment. The asterisk denotes differences, *:
P < 0.05. Values are shown as mean r SEM. 㻌
46
Table 2.5. Follicular fluid sex steroids concentration on Day 9.
W1DF
W2DF
P-value
P4 (ng/ml)
90.1㼼11.8
91.4㼼7.7
NS
E2 (ng/ml)
82.5㼼20.7
64.1㼼8.7
NS
Values are mean 㼼 SEM.
Day 9 = The day of after 24h of GnRH treatment.
W1DF = Dominant follicle (DF) in the first follicular wave.
W2DF = DF in the second follicular wave.
47
COX-2
PGES
0.16
2.5
0.12
/GAPDH
/GAPDH
2.0
1.5
1.0
0.08
0.5
0.04
0
0
W1DF
W1 W2DF
W2
W1 W2DF
W2
W1DF
PGFS
/GAPDH
0.8
0.6
0.4
0.2
0
W1DF
W1
W2DF
W2
Fig. 2.11.
The relative amounts of mRNA of COX-2, PGES and PGFS of W1DF
and W2DF granulosa cells on Day 9. In each figure, the black bar
indicates W1DF and the white bar indicates W2DF. W1DF; Dominant
follicle (DF) in the first follicular wave. W2DF;DF in the second
follicular wave. Day9 = the day of after 24h of GnRH treatment. Values
are shown as mean r SEM. 㻌
48
iNOS
eNOS
ͤ
.
0.012
0.02
/GAPDH
/GAPDH
0.025
0.015
0.01
0.08
0.04
0.005
0
0
W1DF
W1
W1DF
W1
W2DF
W2
W2DF
W2
Fig. 2.12.
The relative amounts of mRNA of iNOS and eNOS in W1DF and
W2DF granulosa cells on Day 9. In each figure, the black bar
indicates W1DF and the white bar indicates W2DF. W1DF;
Dominant follicle (DF) in the first follicular wave. W2DF;DF in the
second follicular wave. Day9 = the day of after 24h of GnRH
treatment. The asterisk denotes differences,
shown as mean r SEM. 㻌
49
䈜:
P < 0.1. Values are
VEGF120
VEGF164
*
ͤ
1.4
0.5
1.2
0.4
/GAPDH
/GAPDH
1.0
0.8
0.6
0.3
0.2
0.4
0.1
0.2
0
0
W1
W1DF
W1
W1DF
W2
W2DF
W2
W2DF
FGF-2
ͤ
2.5
/GAPDH
2.0
1.5
1.0
0.5
0
W1
W1DF
W2
W2DF
Fig. 2.13.
The relative amounts of mRNA of VEGF120, VEGF164 and FGF-2 in
W1DF and W2DF granulosa cells on Day 9. In each figure, the black
bar indicates W1DF and the white bar indicates W2DF. W1DF;
Dominant follicle (DF) in the first follicular wave. W2DF;DF in the
second follicular wave. Day9 = the day of after 24h of GnRH treatment.
The asterisk denotes differences,
䈜:
shown as mean r SEM. 㻌
50
P < 0.1, *: P < 0.05. Values are
StAR
P450-scc
ͤ
16
25
14
20
12
/GAPDH
/GAPDH
*
18
30
15
10
8
6
10
4
5
2
0
0
W1
W1DF
W2
W2DF
W1
W1DF
W2
W2DF
3β-HSD
*
140
120
/GAPDH
100
80
60
40
20
0
W1
W1DF
W2
W2DF
Fig. 2.14.
The relative amounts of mRNA of StAR, P450-scc, and 3E-HSD in W1DF
and W2DF granulosa cells on Day 9. In each figure, the black bar indicates
W1DF and the white bar indicates W2DF. W1DF; Dominant follicle (DF) in
the first follicular wave. W2DF;DF in the second follicular wave. Day9 = the
day of after 24h of GnRH treatment. The asterisk denotes differences, 䈜: P <
0.1, *: P < 0.05. Values are shown as mean r SEM. 㻌
51
Ovulation
Color Doppler US
W1CL
W2CL
Day10
Day11
Day12
Day13
Day14
Day15
Day16
Day17
Day18
Day19
Day20
Day21
Fig. 2.15.
Schematic diagram of experimental model of W1CL and W2CL in Experiment 4.
Day 0 = The day of spontaneous ovulation. Day10 = The day of W1DF or W2DF
ovulation. W1DF; Dominant follicle (DF) in the first follicular wave. W2DF;DF
in the second follicular wave. W1CL; Corpus luteum (CL) formed after ovulation
of W1DF. W2CL; CL formed after ovulation of W2DF. B-mode US = transrectal ultrasonography. Color Doppler US = trans-rectal color Doppler
ultrasonography.
52
Table 2.6. Diameter and blood flow in the follicular wall on Day 9.
W1DF
W2DF
P-value
Diameter (mm)
17.7㼼0.3
15.7㼼0.5
P 0.01
BF%(%)
55.3㼼4.0
36.1㼼2.3
P 0.01
Values are mean 㼼 SEM.
Day 9 = The day of after 24h of GnRH treatment.
W1DF = Dominant follicle (DF) in the first follicular wave.
W2DF = DF in the second follicular wave.
BF% = The percentage of follicle circumference with blood flow signals.
53
Cross-sectional area of corpus luteum (mm2)
䠆
700
W1CL
W2CL
600
䠆
䠆
500
400
300
G : P < 0.01
D : P < 0.01
200
G,D : P < 0.05
100
0
12
15
18
21
Days from follicular wave emergence
Fig. 2.16.
Comparative changes of cross-sectional area of corpus luteum (CL) of
W1CL and W2CL on Day 12, 15, 18 and 21. Day 10 = ovulation day of
W1DF and W2DF. W1DF; Dominant follicle (DF) in the first follicular
wave. W2DF;DF in the second follicular wave. W1CL; CL formed after
ovulation of W1DF. W2CL; CL formed after ovulation of W2DF. Effect
of group (G) (P < 0.01), day (D) (P < 0.01) and interaction between
group and day (G,D)(P < 0.05). The asterisk denotes difference between
each point, : P < 0.05. Values are mean r SEM of each point.㻌
54
Blood flow area of corpus luteum (mm2)
500
W1CL
W2CL
400
䠆
䠆
300
G : P < 0.05
D : P < 0.05
G,D : P < 0.05
200
100
0
12
15
18
21
Days from follicular wave emergence
Fig. 2.17.
Comparative changes of blood flow area in the corpus luteum (CL) of
W1CL and W2CL on Day 12, 15, 18 and 21. Day 10 = ovulation
day of W1DF and W2DF. W1DF; Dominant follicle (DF) in the first
follicular wave. W2DF;DF in the second follicular wave. W1CL; CL
formed after ovulation of W1DF. W2CL; CL formed after ovulation
of W2DF. Effect of group (G) (P < 0.05), day (D) (P < 0.05) and
interaction between group and day (G,D)(P < 0.05). The asterisk
denotes difference between each point, : P < 0.05. Values are mean
r SEM of each point. 㻌
55
Plasma P4 concentration (ng/ml)
7.0
W1CL
W2CL
6.0
5.0
4.0
3.0
G : P < 0.05
G:P<0.05
D:P<0.05
G,D : NS
GD:NS
2.0
D : P < 0.05
1.0
0
10 11 12 13 14 15 16 17 18 19 20 21
Days from follicular wave emergence
Fig. 2.18.
Comparative changes in the plasma P4 concentration of W1CL and
W2CL. Blood samples were collected daily from Day 10 to 21. Day
10 = ovulation day of W1DF and W2DF. W1DF; Dominant follicle
(DF) in the first follicular wave. W2DF;DF in the second follicular
wave. W1CL; Corpus luteum (CL) formed after ovulation of W1DF.
W2CL; CL formed after ovulation of W2DF. Effect of group (G) (P <
0.05), day (D) (P < 0.05) and interaction between group and day
(G,D)(NS). Values are mean r SEM of each point. 㻌
56
➨㸱❶
➨ 1 ༸⬊Ἴ୺ᖍ༸⬊㸦W1DF㸧ࡢⓎ⫱ࢆไᚚࡍࡿせᅉ
57
3㸫1㸬ᗎㄽ
➨ 2 ❶ࡼࡾ㸪W1DF ࡢⓎ⫱ືែ㸪ᶵ⬟㸪᤼༸๓ᚋࡢᛶ㉁࠾ࡼࡧ᤼༸ᚋ࡟ᙧᡂࡉࢀࡿ㯤
యࡢᛶ㉁ࢆ W2DF ࡜ẚ㍑ࡍࡿࡇ࡜࡛᫂ࡽ࠿࡟ࡋࡓࠋࡲࡓ㸪୧⪅ࡢᛶ㉁ࡢ㐪࠸ࢆࡶࡓࡽࡍ
せᅉ࡜ࡋ࡚㸪ᮎᲈ⾑୰ࡢ P4 ⃰ᗘࡢ㐪࠸࡟ࡼࡿ LH ࣃࣝࢫ㢖ᗘࡢ㐪࠸ࡀ᥎ ࡉࢀࡓ㸦15㸪
52㸧
ࠋAdams ࡽ㸦5㸧ࡣⓎ᝟┤ᚋࡢ࢘ࢩ࡟⭐ෆ␃⨨ᆺ P4 〇๣ࢆᤄධࡋࡓ࡜ࡁ㸪W1DF ࡢ
᭱኱┤ᚄࡀ↓ฎ⨨⩌࡜ẚ㍑ࡋ࡚ᑠࡉ࠸ࡇ࡜ࢆ♧ࡋ࡚࠸ࡿࠋࡇࡢࡇ࡜࠿ࡽ㸪W1DF ࡢᛶ㉁
ࢆᕥྑࡍࡿせᅉ࡜ࡋ࡚㸪Ⓨ⫱ᮇ㛫୰ࡢ⾑୰ P4 ⃰ᗘ࡟ࡼࡿᙳ㡪ࡀ⪃࠼ࡽࢀࡿࠋࡋ࠿ࡋ࡞ࡀ
ࡽ㸪↓ฎ⨨≧ែ࡛ࡢ W1DF ࡢⓎ⫱ࢆไᚚࡍࡿせᅉࡣ㸪㐣ཤ࡟࠾࠸࡚༑ศ࡟᫂ࡽ࠿࡟ࡉࢀ
࡚ࡣ࠸࡞࠸ࠋࡑࡇ࡛㸪ᮏ❶࡛ࡣ༸⬊Ⓨ⫱ᮇ㛫୰ࡢ⾑୰ P4 ⃰ᗘࡀ༸⬊ࡢⓎ⫱࡟ཬࡰࡍᙳ㡪
ࢆㄪ࡭ࡓࠋࡉࡽ࡟㸪W1DF ࡣ㯤య࡜ྠ୍༸ᕢෆ࡛Ⓨ⫱ࡍࡿ㸦ඹᏑ㸧࠿㸪཯ᑐഃࡢ༸ᕢ࡛
Ⓨ⫱ࡍࡿ㸦㠀ඹᏑ㸧࠿ࡢ࡝ࡕࡽ࠿࡛࠶ࡿࠋࡇࢀࡲ࡛㸪W1DF ࡜㯤యࡢඹᏑࡲࡓࡣ㠀ඹᏑ
ࡢⓎ⏕⋡ࡣኚࢃࡽ࡞࠸࡜࠸࠺ሗ࿌ࡀ࠶ࡾ㸦40㸧
㸪୍᪉࡛ඹᏑࡢⓎ⏕⋡ࡀ㧗࠸࡜࠸࠺ሗ࿌ࡶ
࠶ࡿ㸦33㸧
ࠋࡋ࠿ࡋ࡞ࡀࡽ㸪W1DF ࡜㯤యࡢඹᏑࡲࡓࡣ㠀ඹᏑࡀ W1DF ࡢⓎ⫱ືែࡸ༸
⬊ࡢᶵ⬟࡟୚࠼ࡿᙳ㡪ࡣ༑ศ࡟ࡣ᳨ウࡉࢀ࡚࠸࡞࠸ࠋࡑࡇ࡛㸪ᮏ❶࡛ࡣ㸪༸ᕢෆᒁᡤ⎔
ቃࡀ༸⬊ࡢᛶ㉁࡟ᙳ㡪ࢆ୚࠼ࡿྍ⬟ᛶࢆ᥈ࡿࡓࡵ㸪ඹᏑ࡜㠀ඹᏑ࡜ࡢ㛫࡛ࡢ W1DF ࡢⓎ
⫱ືែ㸪༸⬊ᾮ୰ࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥࢆ ᐃࡋ㸪ẚ㍑ࡋࡓࠋ
3㸫2㸬ヨ㦂 1㸸༸⬊ἼⓎ⌧࠿ࡽ 7 ᪥┠ࡢ W1DF ࡢ┤ᚄ࡜⾑୰ P4 ⃰ᗘࡢ┦㛵㛵ಀ࠾ࡼࡧ
W1DF ࡜㯤యࡢඹᏑࡲࡓࡣ㠀ඹᏑ㛵ಀࡀ W1DF ࡢ┤ᚄ࡟ཬࡰࡍᙳ㡪 3㸫2㸫1㸬౪ヨື≀
58
⮫ᗋⓗ࡟೺ᗣ࡛㸪ṇᖖ࡞Ⓨ᝟࿘ᮇࢆ᭷ࡍࡿ࣍ࣝࢫࢱ࢖ࣥ✀㠀Ἢங∵ 30 㢌㸦ᖹᆒᖺ㱋㸸
6.1 r 0.4 ṓ㸪ᖹᆒ±ᶆ‽ㄗᕪ) ࢆ⏝࠸࡚㸪ᘏ࡭ 44 㢌ࡢࢹ࣮ࢱࢆゎᯒ࡟฼⏝ࡋࡓࠋ࢘ࢩࡣ
ᖏᗈ␆⏘኱Ꮫ␆⏘ࣇ࢕࣮ࣝࢻ⛉Ꮫࢭࣥࢱ࣮ෆࡢࣃࢻࢵࢡ࡟࡚㸪ࢥ࣮ࣥࢧ࢖࣮ࣞࢪ㸪஝ⲡ
࠾ࡼࡧ⃰ཌ㣫ᩱࡀΰྜࡉࢀࡓ TMR ࢆ⤥୚ࡉࢀ㸪
⮬⏤㣧Ỉ࡛ࡁࡿ≧ἣ࡛㣫㣴ࡉࢀ࡚࠸ࡓࠋ
ᐇ㦂ෆᐜࡣᖏᗈ␆⏘኱Ꮫࡢᐇ㦂೔⌮ጤဨ఍࡟࡚ᢎㄆࡉࢀ࡚࠸ࡿࠋ
3㸫2㸫2㸬ᐇ㦂᪉ἲ
⮬↛Ⓨ᝟㛤ጞᚋ㸪12 ᫬㛫ࡈ࡜࡟㉸㡢Ἴ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚༸ᕢࢆほᐹࡋ㸪᤼༸๓༸
⬊ࡢᾘኻࢆ☜ㄆࡋࡓ᫬Ⅼࢆ Day 0 ࡜ࡋࡓࠋDay 6 ࡟㉸㡢Ἴ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚ W1DF
ࡢほᐹࢆ⾜ࡗࡓࠋࡇࡢ᫬㸪㯤య࡜ W1DF ࡀྠ୍༸ᕢෆ࡟ᏑᅾࡍࡿඹᏑ㛵ಀ࠿㸪ࡑࢀࡒࢀ
ࡀูࡢ༸ᕢ࡟Ꮡᅾࡍࡿ㠀ඹᏑ㛵ಀ࡛࠶ࡿࡢ࠿ࢆ☜ㄆࡋࡓࠋࡲࡓ㸪29 㢌࠿ࡽṇ୰ᑿ㟼⬦ࡼ
ࡾ᥇⾑ࢆ⾜ࡗࡓࠋ
3㸫2㸫3㸬 ༸⬊ᙧែࡢほᐹ
୺ᖍ༸⬊ࡢᖹᆒ┤ᚄࡣ㸪5.0MHzࡢࣜࢽ࢔ࣉ࣮ࣟࣈࡀ௜ᒓࡋࡓ⤒┤⭠㉸㡢Ἴ⏬ീデ᩿⿦
⨨㸦HS̺101V㸪ᮏከ㟁Ꮚ㸪ឡ▱㸧ࢆ⏝࠸࡚ ᐃࡋࡓࠋࣉ࣮ࣟࣈࢆᡭᣦ࡜࡜ࡶ࡟┤⭠ෆ࡟
ᤄධࡋ㸪ᕥྑ୧ഃ༸ᕢࡢ᩿ᒙീࢆほᐹࡋࡓࠋ୺ᖍ༸⬊ࡢ༸⬊᩿ᒙ⏬ീࡀ᭱኱࡟࡞ࡿࡼ࠺㟼
Ṇ⏬ࢆグ㘓ࡋ㸪ࣃࢯࢥࣥୖ࡟㟼Ṇ⏬ࢆ⛣ືࡉࡏ㸪୺ᖍ༸⬊ࡣ㛗ᚄ࡜▷ᚄࡢᖹᆒ್ࢆᖹᆒ┤
ᚄ࡜ࡋ㸪ࢹ࣮ࢱ࡜ࡋ࡚⏝࠸ࡓࠋ
3㸫2㸫4㸬᥇⾑
21G᥇⾑㔪࡜࣊ࣃࣜࣥຍ┿✵᥇⾑⟶㸦࣋ࣀࢪ࢙ࢡࢺϩ┿✵᥇⾑⟶㸪TERUMO㸪ᮾி㸪᪥
ᮏ㸧ࢆ⏝࠸࡚ᑿ㟼⬦ࡼࡾ10mlࡢ᥇⾑ࢆ⾜ࡗࡓࠋ᥇ྲྀࡋࡓ⾑ᾮࡣịỈ୰࡟࡚ᛴ෭ᚋ㸪4Υ࡛
2,000 g㸪20ศ㛫㐲ᚰࡋ㸪⾑₢ศ㞳ᚋ㸪⾑୰P4⃰ᗘ ᐃࡲ࡛㸫30Υ࡟࡚෾⤖ಖᏑࡋࡓࠋ
59
3㸫2㸫5㸬⾑୰P4⃰ᗘࡢ ᐃ
Day 6࡟࠾ࡅࡿ⾑୰P4⃰ᗘࡣEIA࡟ࡼࡾ ᐃࡋࡓࠋ ᐃࡣ➨2❶࡜ྠᵝࡢ᪉ἲ࡛⾜ࡗࡓࠋ
ᐃෆኚື࠾ࡼࡧ ᐃ㛫ኚືࡣࡑࢀࡒࢀ5.2㸣࠾ࡼࡧ7.4%࡛࠶ࡗࡓࠋ
3㸫2㸫6㸬⤫ィฎ⌮
Day 6 ࡟࠾ࡅࡿ୺ᖍ༸⬊ࡢᖹᆒ┤ᚄ࡜⾑୰ P4 ⃰ᗘࡢ┦㛵ᛶࢆㄪ࡭ࡿࡓࡵ࡟ࡣ㸪᭱ᑠ 2
஌ἲ࡟ࡼࡾᅇᖐ┤⥺ᘧࢆồࡵ㸪Pearson ࡢ┦㛵ಀᩘࢆồࡵ࡚┦㛵ࡢ᭷ពᛶࢆ᳨ᐃࡋࡓࠋ⤖
ᯝࡣࡍ࡭࡚ᖹᆒ್±ᶆ‽ㄗᕪ࡛♧ࡋࡓࠋඹᏑ⩌࡜㠀ඹᏑ⩌ࡢ㛫࡛ Day 6 ࡟࠾ࡅࡿ୺ᖍ༸⬊
ࡢᖹᆒ┤ᚄ࡜⾑୰ P4 ⃰ᗘࡢẚ㍑࡟ࡣ㸪F ᳨ᐃࢆ⾜࠸ศᩓࡢᆒ୍ᛶࢆ☜ㄆࡋࡓᚋ㸪Student
ࡢ t ᳨ᐃࢆ⏝࠸ࡓࠋP < 0.05 ࡢሙྜࢆ᭷ពᕪ࠶ࡾ࡜ࡋࡓࠋ⤫ィฎ⌮࡟ࡣ⤫ィฎ⌮ࢯࣇࢺ࡛
࠶ࡿ StatView㸦Abacus Concepts㸪Inc.㸪Berkeley㸪CA㸪USA㸧ࢆ⏝࠸ࡓࠋ
3㸫3㸬ヨ㦂 2㸸W1DF ࡜㯤యࡢඹᏑࡲࡓࡣ㠀ඹᏑ㛵ಀࡀ༸⬊ἼⓎ⌧᪥࠿ࡽ 5 ᪥┠ࡲ࡛ࡢ
W1DF ࡜㯤యࡢⓎ⫱ືែ㸪⾑୰ P4 ⃰ᗘ㸪࠾ࡼࡧ༸⬊ᾮࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥ⃰ᗘ࡟
ཬࡰࡍᙳ㡪 3㸫3㸫1㸬౪ヨື≀
⮫ᗋⓗ࡟೺ᗣ࡛㸪ṇᖖ࡞Ⓨ᝟࿘ᮇࢆ᭷ࡍࡿ࣍ࣝࢫࢱ࢖ࣥ✀㠀Ἢங∵ 5 㢌㸦ᖹᆒᖺ㱋㸸
5.6 r 1.0 ṓ㸪ᖹᆒ±ᶆ‽ㄗᕪ) ࢆ⏝࠸ࡓࠋ࢘ࢩࡣᖏᗈ␆⏘኱Ꮫ␆⏘ࣇ࢕࣮ࣝࢻ⛉Ꮫࢭࣥࢱ
࣮ෆࡢࣃࢻࢵࢡ࡟࡚㸪ࢥ࣮ࣥࢧ࢖࣮ࣞࢪ㸪஝ⲡ࠾ࡼࡧ⃰ཌ㣫ᩱࡀΰྜࡉࢀࡓ TMR ࢆ⤥
୚ࡉࢀ㸪⮬⏤㣧Ỉ࡛ࡁࡿ≧ἣ࡛㣫㣴ࡉࢀ࡚࠸ࡓࠋᐇ㦂ෆᐜࡣᖏᗈ␆⏘኱Ꮫࡢᐇ㦂೔⌮ጤ
ဨ఍࡟࡚ᢎㄆࡉࢀ࡚࠸ࡿࠋ
60
3㸫3㸫2㸬ᐇ㦂᪉ἲ
⮬↛Ⓨ᝟㛤ጞᚋ㸪12 ᫬㛫ࡈ࡜࡟㉸㡢Ἴ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚༸ᕢࢆほᐹࡋ㸪᤼༸๓༸
⬊ࡢᾘኻࢆ☜ㄆࡋࡓ᫬Ⅼࢆ Day 0 ࡜ࡋࡓࠋ
Day 0 ࠿ࡽ 4 ࡟࠿ࡅ࡚㉸㡢Ἴ⏬ീデ᩿⿦⨨ࢆ⏝
࠸࡚ W1DF ࠾ࡼࡧ㯤యࡢほᐹࢆ⾜ࡗࡓࠋࡲࡓ㸪Day 4 ࡢ᫬Ⅼ࡛ W1DF ࡀ㯤య࡜ྠ୍༸ᕢ
ෆ࡟ᏑᅾࡍࡿಶయࢆඹᏑ⩌㸪W1DF ࡀ㯤య࡜཯ᑐഃࡢ༸ᕢ࡟Ꮡᅾࡍࡿሙྜࢆ㠀ඹᏑ⩌࡜
ศ㢮ࡋࡓࠋࡲࡓ㸪Day 0 ࠿ࡽ 4 ࡟࠿ࡅ࡚㐃᪥ṇ୰ᑿ㟼⬦ࡼࡾ᥇⾑ࢆ⾜ࡗࡓࠋࡑࡋ࡚㸪Day
4 ࡟ W1DF ࡢ༸⬊ᾮ࠾ࡼࡧ㢛⢏ᒙ⣽⬊ࡢᅇ཰ࢆ⤒⭐༸⬊྾ᘬἲ࡟ࡼࡾ⾜ࡗࡓࠋ
5 㢌ࡢ౪ヨ∵ࡣ㸪ࣛࢸࣥ᱁Ꮚἲ࡟ࡼࡿࢡࣟࢫ࣮࢜ࣂ࣮ヨ㦂ࢆ⾜ࡗࡓࡓࡵ㸪ඹᏑ⩌㸦n㸻
5㸧࠾ࡼࡧ㠀ඹᏑ⩌㸦n㸻5㸧࡟ࡣࡑࢀࡒࢀ 5 㢌ࡢ౪ヨ∵ࡀ 1 ᅇࡎࡘྵࡲࢀ࡚࠸ࡿࠋ
3㸫3㸫3㸬༸⬊࠾ࡼࡧ㯤యᙧែࡢほᐹ
୺ᖍ༸⬊ࡢᖹᆒ┤ᚄ࠾ࡼࡧ㯤యࡢ᩿㠃✚ࡣ㸪5.0MHzࡢࣜࢽ࢔ࣉ࣮ࣟࣈࡀ௜ᒓࡋࡓ⤒┤
⭠㉸㡢Ἴ⏬ീデ᩿⿦⨨㸦HS̺101V㸪ᮏከ㟁Ꮚ㸪ឡ▱㸪᪥ᮏ㸧ࢆ⏝࠸࡚ ᐃࡋࡓࠋࣉ࣮ࣟ
ࣈࢆᡭᣦ࡜࡜ࡶ࡟┤⭠ෆ࡟ᤄධࡋ㸪ᕥྑ୧ഃ༸ᕢࡢ᩿ᒙീࢆほᐹࡋࡓࠋ୺ᖍ༸⬊ࡢ༸⬊᩿
ᒙ⏬ീࡀ᭱኱࡟࡞ࡿࡼ࠺㟼Ṇ⏬ࢆグ㘓ࡋ㸪ࣃࢯࢥࣥୖ࡟㟼Ṇ⏬ࢆ⛣ືࡉࡏ㸪୺ᖍ༸⬊ࡣ㛗
ᚄ࡜▷ᚄࡢᖹᆒ್ࢆᖹᆒ┤ᚄ࡜ࡋ㸪ࢹ࣮ࢱ࡜ࡋ࡚⏝࠸ࡓࠋ㯤యࡢ᩿㠃✚ࡣ㸪㯤యࡢ᩿ᒙ⏬
ീࡀ᭱኱࡟࡞ࡿࡼ࠺㟼Ṇ⏬ࢆグ㘓ࡋࡓࠋࣃࢯࢥࣥୖ࡟㟼Ṇ⏬ࢆ⛣ືࡉࡏ㸪㯤యࡢ㛗ᚄ࡜▷
ᚄࡢᖹᆒ್࠿ࡽᖹᆒ┤ᚄࢆ⟬ฟࡋ㸪
㸦ᖹᆒ┤ᚄ㸭2㸧2×3.14࡟ᙜ࡚ࡣࡵ㯤య᩿㠃✚ࢆ⟬ฟࡋ㸪
ࢹ࣮ࢱ࡟⏝࠸ࡓࠋ
3㸫3㸫4㸬᥇⾑
21G᥇⾑㔪࡜࣊ࣃࣜࣥຍ┿✵᥇⾑⟶㸦࣋ࣀࢪ࢙ࢡࢺϩ┿✵᥇⾑⟶㸪TERUMO㸪ᮾி㸪᪥
ᮏ㸧ࢆ⏝࠸࡚ᑿ㟼⬦ࡼࡾ10mlࡢ᥇⾑ࢆ⾜ࡗࡓࠋ᥇ྲྀࡋࡓ⾑ᾮࡣịỈ୰࡟࡚ᛴ෭ᚋ㸪4Υ࡛
61
2,000 g㸪20ศ㛫㐲ᚰࡋ㸪⾑₢ศ㞳ᚋ㸪⾑୰P4࠾ࡼࡧE2⃰ᗘ ᐃࡲ࡛㸫30Υ࡟࡚෾⤖ಖᏑࡋ
ࡓࠋ
3㸫3㸫5㸬୺ᖍ༸⬊ࡢ྾ᘬ࡜༸⬊ᾮࡢᅇ཰
୺ᖍ༸⬊ࡢ྾ᘬ㸪༸⬊ᾮࡢᅇ཰࠾ࡼࡧࡑࡢᚋࡢฎ⌮࡜ಖᏑࡣ㸪➨2❶࡜ྠᵝࡢ᪉ἲ࡛⾜
ࡗࡓࠋ
3㸫3㸫6㸬༸⬊ᾮP4㸪E2࠾ࡼࡧA4⃰ᗘࡢ ᐃ
༸⬊ᾮࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥࡢ ᐃࡣ➨2❶࡜ྠᵝࡢ᪉ἲ࡛⾜ࡗࡓࠋࡇࡢ ᐃἲ࡟ࡼࡿP4㸪
E2࠾ࡼࡧA4ࡢᢳฟຠ⋡ࡣࡑࢀࡒࢀ85㸣㸪81㸣࠾ࡼࡧ84㸣࡛࠶ࡗࡓࠋP4ࡢ ᐃෆኚື࠾ࡼࡧ
ᐃෆኚືࡣࡑࢀࡒࢀ5.5%࠾ࡼࡧ7.4%㸪E2ࡢ ᐃෆኚື࠾ࡼࡧ ᐃ㛫ኚືࡣ6.2㸣࠾ࡼࡧ
8.6%㸪A4ࡢ ᐃෆኚື࠾ࡼࡧ ᐃ㛫ኚືࡣࡑࢀࡒࢀ5.6㸣࠾ࡼࡧ7.8%࡛࠶ࡗࡓࠋ
3㸫3㸫7㸬⾑୰P4࠾ࡼࡧE2⃰ᗘࡢ ᐃ
Day 0࠿ࡽ4࡟࠾ࡅࡿ⾑୰P4⃰ᗘ࠾ࡼࡧDay 4ࡢ⾑୰E2⃰ᗘࡣEIA࡟ࡼࡾ ᐃࡋࡓࠋ ᐃ᪉
ἲࡣ➨2❶࡜ྠᵝࡢ᪉ἲ࡛⾜ࡗࡓࠋP4ࡢ ᐃෆኚື࠾ࡼࡧ ᐃ㛫ኚືࡣࡑࢀࡒࢀ5.2㸣࠾ࡼ
ࡧ7.4%㸪E2ࡢ ᐃෆኚື࠾ࡼࡧ ᐃ㛫ኚືࡣࡑࢀࡒࢀ6.0㸣࠾ࡼࡧ8.4㸣࡛࠶ࡗࡓࠋ
3㸫3㸫8㸬⤫ィฎ⌮
⤖ᯝࡣࡍ࡭࡚ᖹᆒ್±ᶆ‽ㄗᕪ࡛♧ࡋࡓࠋ⾑୰ P4 ⃰ᗘ㸪୺ᖍ༸⬊ࡢᖹᆒ┤ᚄ࠾ࡼࡧ㯤
య᩿㠃✚ࡢ᥎⛣ࡢẚ㍑࡟ࡣ㸪2 ඖ㓄⨨ศᩓศᯒࢆ⾜࠸඲యࡢኚ໬ࡢ᭷ពᛶࢆㄪ࡭㸪஺஫
స⏝ࡀ᭷ព࡛࠶ࡗࡓࡶࡢ࡟ᑐࡋ࡚㸪Bartlet ᳨ᐃࢆ⾜࠸ศᩓࡢᆒ୍ᛶࢆ᳨ᐃࡋࡓᚋ㸪
Post-hoc ᳨ᐃ࡜ࡋ࡚ Schefe ࡢከ⩌ẚ㍑᳨ᐃࢆ⾜ࡗࡓࠋDay 4 ࡟࠾ࡅࡿඹᏑ⩌࡜㠀ඹᏑ⩌
㛫࡛ࡢ⾑୰ E2 ⃰ᗘ࠾ࡼࡧ༸⬊ᾮ୰ P4㸪E2 ࠾ࡼࡧ A4 ⃰ᗘࡢ᳨ᐃ࡟ࡣ F ᳨ᐃ࡟ࡼࡾศᩓࡢ
62
ᆒ୍ᛶࢆ᳨ᐃࡋ㸪Student ࡢ t ᳨ᐃࢆ⾜ࡗࡓࠋP < 0.05 ࡢሙྜࢆ᭷ពᕪ࠶ࡾ࡜ࡋࡓࠋ⤫ィ
ฎ⌮࡟ࡣ⤫ィฎ⌮ࢯࣇࢺ࡛࠶ࡿ StatView㸦Abacus Concepts㸪Inc.㸪Berkeley㸪CA㸪USA㸧
ࢆ⏝࠸ࡓࠋ
3㸫4㸬⤖ᯝ
3㸫4㸫1㸬ヨ㦂 1 ⤖ᯝ
ᮏヨ㦂࡛ඹᏑ⩌ࡣ n㸻22㸦ᖹᆒᖺ㱋㸸6.2±0.6㸧
㸪㠀ඹᏑ⩌ࡣ n㸻22㸦ᖹᆒᖺ㱋㸸6.2±0.4㸧
࡛࠶ࡗࡓࠋ᥇⾑ࢆ⾜ࡗࡓ࢘ࢩ㸦n㸻29㸪ᖹᆒᖺ㱋㸸6.1±0.4㸧ࡢ⾑୰ P4 ⃰ᗘࡢᖹᆒ್ࡣ 3.0±0.2
ng/ml ࡛࠶ࡗࡓࠋࡲࡓ㸪ඹᏑ⩌㸦n㸻16㸪ᖹᆒᖺ㱋㸸6.0±0.7㸧࡛ࡢ⾑୰ P4 ⃰ᗘࡢᖹᆒ್ࡣ
㠀ඹᏑ⩌㸦n㸻13㸪ᖹᆒᖺ㱋㸸6.2±0.6㸧࡛ࡢ⾑୰ P4 ⃰ᗘࡢᖹᆒ್࡟ẚ࡭࡚㸪᭷ព࡟ప࠿
ࡗࡓ㸦Table 3.1.㸧
ࠋ
Day 6 ࡟࠾ࡅࡿ⾑୰ P4 ⃰ᗘ࡜୺ᖍ༸⬊┤ᚄ࡜ࡢ┦㛵㛵ಀࢆㄪ࡭ࡓ⤖ᯝ㸪᭷ព࡞┦㛵㛵
ಀࡣほᐹࡉࢀ࡞࠿ࡗࡓ㸦Fig. 3.1.㸧
ࠋࡲࡓ㸪ඹᏑ⩌࡜㠀ඹᏑ⩌ࢆࡑࢀࡒࢀศࡅ࡚┦㛵㛵ಀ
ࢆㄪ࡭ࡓሙྜ㸪୧⩌࡜ࡶ⾑୰ P4 ⃰ᗘ࡜୺ᖍ༸⬊┤ᚄ࡜ࡢ㛫࡟᭷ព࡞┦㛵㛵ಀࡣほᐹࡉࢀ
࡞࠿ࡗࡓ㸦Fig. 3.2.㸧
ࠋ
ඹᏑ⩌࡜㠀ඹᏑ⩌࡛ Day 6 ࡟࠾ࡅࡿ୺ᖍ༸⬊ࡢᖹᆒ┤ᚄࢆẚ㍑ࡋࡓ࡜ࡇࢁඹᏑ⩌࡛᭷
ព࡟኱ࡁ࠿ࡗࡓ㸦Table 3.2.㸧
ࠋ
3㸫4㸫2㸬ヨ㦂 2 ⤖ᯝ
ඹᏑ⩌࡜㠀ඹᏑ⩌ࡢ୺ᖍ༸⬊ࡢᖹᆒ┤ᚄࡢ᥎⛣ࢆ Fig. 3.3.࡟♧ࡋࡓࠋඹᏑ⩌࡛ Day 2 ࠿
ࡽ 4 ࡟࠿ࡅ࡚㠀ඹᏑ⩌࡟ẚ㍑ࡋ࡚኱ࡁࡃ᥎⛣ࡋ࡚࠸ࡓࡀ㸪᭷ព࡞ᕪࡣࡳࡽࢀ࡞࠿ࡗࡓࠋ
ඹᏑ⩌࡜㠀ඹᏑ⩌ࡢ㯤య᩿㠃✚࠾ࡼࡧ⾑୰ P4 ⃰ᗘ᥎⛣ࢆ Fig. 3.4.࡜ Fig. 3.5.࡟ࡑࢀࡒࢀ♧
ࡋࡓࠋ㯤య᩿㠃✚࠾ࡼࡧ⾑୰ P4 ⃰ᗘ᥎⛣ඹ࡟୧⩌㛫࡛ᕪࡣ࡞࠿ࡗࡓࠋ
63
Day 4 ࡟࠾ࡅࡿ⾑୰ E2 ⃰ᗘࢆẚ㍑ࡋࡓ࡜ࡇࢁ㸪ඹᏑ⩌࡛㧗࠸ഴྥࢆ♧ࡋࡓࠋDay 4 ࡟
࠾ࡅࡿ༸⬊ᾮ୰ࡢᛶࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥ⃰ᗘࢆ Table 3.4.࡟♧ࡋࡓࠋ༸⬊ᾮ E2 ⃰ᗘ࠾ࡼࡧ
A4 ⃰ᗘ࡟ᕪࡣࡳࡽࢀ࡞࠿ࡗࡓࡀ㸪༸⬊ᾮ P4 ⃰ᗘࡣඹᏑ⩌࡛᭷ព࡟㧗࠿ࡗࡓࠋ
3㸫5㸬⪃ᐹ
ᮏヨ㦂࡟࠾࠸࡚㸪ヨ㦂 1 ࠿ࡽ Day 6 ࡢ⾑୰ P4 ⃰ᗘࡣ W1DF ࡢ┤ᚄ࡟ᙳ㡪ࢆ୚࠼࡞࠸ࡇ
࡜ࢆ♧ࡋࡓࡀ㸪W1DF ࡜㯤య࡜ࡢ༸ᕢෆ࡛ࡢඹᏑࡲࡓࡣ㠀ඹᏑ㛵ಀࡀ୺ᖍ༸⬊ࡢ┤ᚄࡸ
⾑୰ P4 ⃰ᗘ࡟ᙳ㡪ࢆ୚࠼ࡿࡇ࡜ࡀ♧ࡉࢀࡓࠋࡉࡽ࡟㸪ヨ㦂 2 ࡛ࡣඹᏑ⩌࡟࠾࠸࡚㸪⾑୰
E2 ⃰ᗘ࠾ࡼࡧ༸⬊ᾮ୰ P4 ⃰ᗘࡀ㧗್ࢆ♧ࡋࡓࡇ࡜࠿ࡽ㸪W1DF ࡢⓎ⫱ࡸᛶ㉁ࢆไᚚࡍࡿ
せᅉ࡜ࡋ࡚㸪༸ᕢෆ࡛ࡢ㯤య࡜ࡢඹᏑࡲࡓࡣ㠀ඹᏑ≧ែࡀ኱ࡁࡃᙳ㡪ࢆཬࡰࡍࡇ࡜ࡀ᫂
ࡽ࠿࡟࡞ࡗࡓࠋ
➨ 2 ❶࡟࠾࠸࡚㸪
W1DF ࡜ W2DF ࡢẚ㍑࡛ࡣ୺ᖍ༸⬊ࡢⓎ⫱࡟ࡣ⾑୰ P4 ⃰ᗘࡀ኱ࡁࡃ
㛵୚ࡍࡿࡇ࡜ࢆ♧ࡋࡓࡀ㸪Day 6 ࡟࠾ࡅࡿ W1DF ࡢᖹᆒ┤ᚄ࡜⾑୰ P4 ⃰ᗘ࡟┦㛵㛵ಀࡣ
ࡳࡽࢀ࡞࠿ࡗࡓࠋ⮬↛Ⓨ᝟ᚋࡢ᤼༸☜ㄆ᫬࡟⭐ෆ␃⨨ᆺ P4 〇๣ࢆᤄධࡋࡓ࡜ࡁࡢ㸪༸ᕢ
ෆ࡛Ⓨ⫱ࡍࡿ W1DF ࡢⓎ⫱ືែࢆほᐹࡋࡓ◊✲࡛ࡣ㸪ᤄධࡋ࡞࠿ࡗࡓ∵࡟ẚ࡭᭱኱࡟㐩
ࡋࡓ࡜ࡁࡢᖹᆒ┤ᚄࡀᑠࡉ࠸ࡇ࡜ࢆሗ࿌ࡋ࡚࠸ࡿ㸦5㸧
ࠋࡇࡢࡇ࡜ࡣ㸪୺ᖍ༸⬊Ⓨ⫱ᮇ㛫
୰ࡢ⾑୰ P4 ⃰ᗘ࡟ࡼࡾ୺ᖍ༸⬊ࡢⓎ⫱ࡀไᚚࡉࢀࡿࡇ࡜ࢆព࿡ࡋ࡚࠸ࡿࠋࡋ࠿ࡋ࡞ࡀࡽ㸪
ୖグࡢሗ࿌ࡣ㸪⭐ෆ␃⨨ᆺ P4 〇๣ࢆᤄධࡋࡓ࢘ࢩࢆ⏝࠸ࡓヨ㦂࡛࠶ࡾ㸪W1DF ࡢⓎ⫱ᮇ
㛫୰ࢆ㏻ࡋ࡚ᖖ࡟⾑୰ P4 ⃰ᗘࡣ㧗್࡛࠶ࡿࡇ࡜࠿ࡽ㸪
➨ 2 ❶࡟࠾ࡅࡿ W2DF ࡢ㧗࠸⾑୰
P4 ⃰ᗘ᮲௳ୗ࡛ࡢⓎ⫱⎔ቃ࡟㢮ఝࡋࡓࡶࡢ࡛࠶ࡿ࡜⪃࠼ࡽࢀࡿࠋࡑࡢࡓࡵ㸪⮬↛Ⓨ⫱᮲
௳ୗ࡛ࡢ Day 6 ࡟࠾ࡅࡿ⾑୰ P4 ⃰ᗘࡣ㸪W1DF ࡟኱ࡁ࡞ᙳ㡪ࢆ୚࠼࡞࠸࡜᥎ ࡉࢀࡓࠋ
Ginther ࡽ㸦42㸧ࡣᮍ⤒⏘∵ࢆ⏝࠸ࡓヨ㦂࡟࠾࠸࡚㸪㯤య࡜ྠ୍༸ᕢෆ࡛ඹᏑࡍࡿ W1DF
ࡣ཯ᑐഃࡢ༸ᕢ࡟Ꮡᅾࡍࡿ W1DF ࡜ẚ㍑ࡋ࡚ᖹᆒ┤ᚄࡀᑠࡉ࠸ࡇ࡜ࢆሗ࿌ࡋ࡚࠸ࡿࠋ⤒
⏘㠀Ἢங∵ࢆ⏝࠸ࡓᮏヨ㦂࡟࠾࠸࡚ࡶ㸪ྠᵝࡢ⤖ᯝࡀᚓࡽࢀࡓࠋ࣮࢝ࣛࢻࣉࣛࢆ⏝࠸ࡓ
64
◊✲࡛㸪㯤య࡜ W1DF ࡀྠ୍༸ᕢෆ࡛Ⓨ⫱ࡋࡓሙྜ㸪W1DF ࡀ㯤య࡜཯ᑐഃࡢ༸ᕢ࡛Ⓨ
⫱ࡋࡓሙྜ࡟ẚ࡭㸪༸ᕢෆࡢ⾑⟶᢬ᢠ್ࡀపୗࡋ࡚࠾ࡾ㸪W1DF ࡢ༸⬊ቨ⾑ὶࡀ㧗࠸ࡇ
࡜ࡀ♧ࡉࢀ࡚࠸ࡿ㸦42㸧
ࠋᮏヨ㦂࡟࠾࠸࡚ࡶྠᵝࡢ⌧㇟ࡀ⏕ࡌ࡚࠸ࡓ࡜᥎ ࡉࢀࡿࠋ㐣ཤ
ࡢሗ࿌࡟࠾࠸࡚㸪༸⬊ቨ⾑ὶࡣ㸪༸⬊ࡢᶵ⬟ࢆホ౯ࡍࡿࡢ࡟᭷⏝࡛࠶ࡿ࡜ࡉࢀ࡚࠸ࡿࡓ
ࡵ㸦2㸪42㸪84㸪86㸧
㸪ඹᏑ⩌ࡢ W1DF ࡟ࡼࡾከࡃ⾑ᾮࡀ౪⤥ࡉࢀࡿࡇ࡜ࡣ㸪㓟⣲㸪ᰤ㣴
ࡉࡽ࡟ࡣ LH ࡞࡝ࡢᛶ࣍ࣝࣔࣥࡢ౪⤥㔞㸦109㸧ࢆቑࡸࡋ㸪ࡑࡢ⤖ᯝ㸪༸⬊ෆࡢ⣽⬊ࡢቑ
Ṫࡸ࣍ࣝࣔࣥ⏘⏕ࡀቑຍࡋ࡚㸪୺ᖍ༸⬊ࡢⓎ⫱ࢆಁ㐍ࡋࡓ࡜⪃࠼ࡽࢀࡿࠋ୍᪉࡛㸪ᮏヨ
㦂࡛ࡣ㸪Day 6 ࡟࠾ࡅࡿ⾑୰ P4 ⃰ᗘࢆඹᏑ⩌࡜㠀ඹᏑ⩌࡛ẚ㍑ࡋࡓ࡜ࡇࢁ㸪㠀ඹᏑ⩌࡛
᭷ព࡟㧗࠸ࡇ࡜ࡀ♧ࡉࢀࡓࠋࡇࡢ⤖ᯝࢆࡶࡓࡽࡋࡓཎᅉࡣ୙࡛᫂࠶ࡾ㸪ᮏヨ㦂࡛ࡣ㯤య
ࡢᖹᆒ┤ᚄࡢࢹ࣮ࢱࢆ♧ࡋ࡚࠸࡞࠸ࡓࡵ㸪㯤యࡢⓎ⫱࡟ᕪ␗ࡀ⏕ࡌࡓࡇ࡜࡟ࡼࡿ⤖ᯝ࡛
࠶ࡿࡢ࠿㸪W1DF ࡀ༸ᕢෆ࡟Ꮡᅾࡍࡿࡇ࡜࡛㯤యᶵ⬟࡟㈇ࡢᙳ㡪ࢆ୚࠼ࡓ⤖ᯝ࡞ࡢ࠿㸪
᫂ࡽ࠿࡟࡛ࡁ࡞࠿ࡗࡓࠋ
ࡑࡇ࡛㸪ヨ㦂 2 ࡛ࡣ㸪ඹᏑ⩌࡜㠀ඹᏑ⩌࡛ࡢ W1DF ࡢᛶ㉁ࢆヲ⣽࡟᳨ウࡍࡿࡓࡵ㸪⤒
⏘Ἢங∵ࢆ⏝࠸࡚㸪ඹᏑ⩌࡜㠀ඹᏑ⩌ࡢ W1DF ࡜㯤యࡢⓎ⫱ືែ㸪⾑୰ P4 ⃰ᗘ࠾ࡼࡧ༸
⬊ᾮࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥ⃰ᗘࢆẚ㍑ࡋࡓࠋヨ㦂 2 ࡛ࡣ㸪Day 0 ࠿ࡽ 4 ࡲ࡛ࡢ㯤యࡢⓎ⫱
⾑୰ P4 ⃰ᗘ࡟㛵ࡋ࡚ࡣ㸪
ືែ࠾ࡼࡧ⾑୰ P4 ⃰ᗘ᥎⛣ࡣඹᏑ⩌࡜㠀ඹᏑ⩌㛫࡛ᕪࡣ࡞ࡃ㸪
ヨ㦂 1 ࡜ྠᵝࡢ⤖ᯝࡣᚓࡽࢀ࡞࠿ࡗࡓࠋࡲࡓ㸪W1DF ࡢᖹᆒ┤ᚄ᥎⛣࡟࠾࠸࡚ࡶඹᏑ⩌
࡛㧗ࡵࡢ᥎⛣ࢆ♧ࡋ࡚࠸ࡓࡀ㸪᭷ព࡞ᕪࡣࡳࡽࢀ࡞࠿ࡗࡓࠋࡇࡢཎᅉ࡜ࡋ࡚㸪ᮏヨ㦂࡛
ࡣ༸⬊ἼⓎ⌧ᚋ 5 ᪥┠ࡲ࡛ࡋ࠿ືែࢆ㏣㊧ࡋ࡚࠾ࡽࡎ㸪ヨ㦂 1 ࡛ࡣ 7 ᪥┠࡟↔Ⅼࢆᙜ࡚
࡚࠸ࡓࡓࡵ㸪ྠᵝࡢ⤖ᯝࡀᚓࡽࢀ࡞࠿ࡗࡓ࡜⪃࠼ࡽࢀࡿࠋDay 4 ࡛ࡢ W1DF ࡢ༸⬊ᾮ୰
ࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥࢆ ᐃࡋࡓ࡜ࡇࢁ㸪ඹᏑ⩌࡛ P4 ⃰ᗘࡀ᭷ព࡟㧗್ࢆ♧ࡋࡓࠋࡋ࠿ࡋ
࡞ࡀࡽ㸪༸⬊ᾮ E2 ⃰ᗘࡸ A4 ⃰ᗘ࡟᭷ព࡞ᕪࡣࡳࡽࢀ࡞࠿ࡗࡓࠋ༸⬊ෆ࡛ࢫࢸࣟ࢖ࢻ࣍
ࣝࣔࣥࡀྜᡂࡉࢀࡿ㐣⛬ࡣ㸪༸⬊ቨࡢෆ༸⬊⭷⣽⬊࡟࠾࠸࡚㸪ࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥࡢᇶ
㉁࡜࡞ࡿࢥࣞࢫࢸ࣮ࣟࣝࡀ⣽⬊ෆ࡟ྲྀࡾ㎸ࡲࢀࡿࡇ࡜࠿ࡽጞࡲࡾ㸪ࡇࡢࢥࣞࢫࢸ࣮ࣟࣝ
65
ࡣࣉࣞࢢࢿࣀࣟࣥ࡟ኚ᥮ࡉࢀ㸪ࡑࡢᚋࣉࣞࢢࢿࣀࣟࣥ࠿ࡽ P4 ࡬࡜ኚ᥮ࡉࢀࡿ㸦22㸧
ࠋࡑ
ࠋࡉࡽ࡟ A4 ࡣ༸⬊⭷⣽⬊࠿ࡽ㢛
ࡢᚋ㸪༸⬊⭷⣽⬊ෆ࡛ P4 ࡣ A4 ࡟ኚ᥮ࡉࢀࡿ㸦31㸪59㸧
⢏ᒙ⣽⬊࡟⛣⾜ࡋࡑࡇ࡛ E2 ࡟ኚ᥮ࡉࢀࡿ㸦12㸧ࡇ࡜࡛༸⬊ෆ࡛ࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥࡀ⏘
⏕ࡉࢀ࡚࠸ࡿࠋ௒ᅇࡢ⤖ᯝ࡛ࡣ㸪A4 ࠾ࡼࡧ E2 ⃰ᗘ࡟ᕪࡣࡳࡽࢀ࡞࠿ࡗࡓࡇ࡜࠿ࡽ㸪ඹᏑ
⩌࠾ࡼࡧ㠀ඹᏑ⩌ࡑࢀࡒࢀࡢ୺ᖍ༸⬊ࡢ༸⬊⭷⣽⬊࠾ࡼࡧ㢛⢏ᒙ⣽⬊ࡢࢫࢸࣟ࢖ࢻ࣍ࣝ
ࣔࣥ⏘⏕⬟࡟ᕪࡣ࡞࠸ࡇ࡜ࡀ᥎ ࡉࢀࡿࠋࡑࡢࡓࡵ㸪༸⬊ᾮ P4 ⃰ᗘࡀඹᏑ⩌࡛㧗࠸⌮⏤
࡜ࡋ࡚㸪༸⬊࡛ࡢ P4 ⏘⏕⬟ࡀ㧗࠿ࡗࡓࡓࡵ࡜᥎ ࡍࡿࡇ࡜ࡣ㞴ࡋ࠸ࠋ㐣ཤࡢሗ࿌࡛㸪༸
ᕢෆ࡛ࡢ୍ࡘࡢື⬦࠿ࡽ㯤య࡜ࡑࡢ㏆㞄ࡢ༸⬊࡟ື⬦ᯞࢆఙࡤࡋ࡚࠸ࡿྍ⬟ᛶࡀ㸪ࣄࢺ
ࡢ༸ᕢࢆ⏝࠸ࡓ◊✲࡛♧ࡉࢀ࡚࠸ࡿ㸦75㸧
ࠋࡇࡢࡇ࡜ࡣ㸪㯤య࠿ࡽࡢ⾑⟶ࡀྠ୍༸ᕢෆ࡟
Ꮡᅾࡍࡿ༸⬊ቨ࡟Ꮡᅾࡍࡿẟ⣽⾑⟶࡜࿀ྜࡍࡿࡇ࡜࡛㸪㯤య࠿ࡽᨺฟࡉࢀࡓ㧗⃰ᗘࡢ P4
ࡀ༸⬊࡟౪⤥ࡉࢀ㸪༸⬊ᾮෆ࡟ᾐ㏱ࡋ࡚࠸ࡿྍ⬟ᛶࡀ⪃࠼ࡽࢀࡿࠋᮏヨ㦂࡛ࡣ㸪ࡑࡢ௬
ㄝࢆド᫂ࡍࡿࢹ࣮ࢱࢆ♧ࡋ࡚࠸࡞࠸ࡀ㸪ᮏヨ㦂࡛ᚓࡽࢀࡓ⤖ᯝࡣ㸪ࡇࡢ௬ㄝࡢྍ⬟ᛶࢆ
♧၀ࡍࡿࡶࡢ࡜⪃࠼ࡽࢀࡿࠋࡲࡓ㸪⾑୰ E2 ⃰ᗘࡣඹᏑ⩌࡛㧗࠸ഴྥࢆ♧ࡋࡓࠋࡇࢀࡣ㸪
Ginther ࡽ㸦42㸧ࡀᮍ⤒⏘∵ࢆ⏝࠸࡚⾜ࡗࡓ◊✲࡛ሗ࿌ࡋ࡚࠸ࡿࡼ࠺࡟㸪㯤య࡜ W1DF
ࡀྠ୍༸ᕢෆ࡛ඹᏑࡍࡿሙྜ㸪W1DF ࡢ༸⬊ቨ⾑ὶࡀ㠀ඹᏑࡢሙྜ࡟ẚ࡭࡚኱ࡁ࠸ࡇ࡜
࠿ࡽ㸪ᮏヨ㦂࡟࠾࠸࡚ࡶ㸪ඹᏑ⩌࡛ࡢ W1DF ࡬ࡢ⾑ᾮ㑏ὶࡀࡼࡾ኱ࡁࡃ㸪୺ᖍ༸⬊ෆ࡛
⏘⏕ࡉࢀࡓ E2 ࡢᨺฟࡀஹ㐍ࡋࡓࡇ࡜ࡀཎᅉ࡜⪃࠼ࡽࢀࡿࠋࡋ࠿ࡋ࡞ࡀࡽ㸪ᮏヨ㦂࡛ࡣ༸
⬊ቨ⾑ὶࡢホ౯ࡣ⾜ࡗ࡚࠾ࡽࡎ㸪༑ศ࡟᳨ド࡛ࡁࡿࢹ࣮ࢱࡣ࡞࠸ࠋ㠀Ἢங⤒⏘∵ࢆ⏝࠸
࡚ࡢ༸⬊ቨ⾑ὶホ౯ࢆ⾜࠸㸪ࡇࡢཎᅉࢆ᫂ࡽ࠿࡟ࡍࡿ◊✲ࢆ⾜ࡗ࡚࠸ࡃᚲせࡀ࠶ࡿ࡜⪃
࠼ࡿࠋ
3㸫6㸬ᑠᣓ
ᮏᐇ㦂࡛ࡣ㸪㠀Ἢங⤒⏘∵ࢆ⏝࠸࡚ W1DF ࡢⓎ⫱ࡸᛶ㉁ࢆไᚚࡍࡿせᅉ㸪ࡲࡓඹᏑ⩌
࡜㠀ඹᏑ⩌࡛ࡢ W1DF ࡢᛶ㉁࡟ࡘ࠸࡚ㄪ࡭ࡓࠋࡑࡢ⤖ᯝ㸪ヨ㦂 1 ࡟࠾࠸࡚᤼༸☜ㄆ᪥࠿
66
ࡽ 7 ᪥┠ࡢ W1DF ࡢᖹᆒ┤ᚄ࡜⾑୰ P4 ⃰ᗘ࡜ࡢ㛫࡟┦㛵㛵ಀࡣ࡞࠸ࡇ࡜ࡀ♧ࡉࢀࡓࡀ㸪
W1DF ࡀ㯤య࡜ྠ୍༸ᕢෆ࡛ඹᏑࡍࡿ࡜㸪ඹᏑࡋ࡞࠸ W1DF ࡟ẚ࡭࡚᤼༸☜ㄆ᪥࠿ࡽ㸵
᪥┠ࡢᖹᆒ┤ᚄࡀ኱ࡁࡃ࡞ࡾ㸪⾑୰ P4 ⃰ᗘࡶ㧗್ࢆ♧ࡍࡇ࡜ࡀ♧ࡉࢀࡓࠋࡇࢀࡽࡢࡇ࡜
࠿ࡽ㸪W1DF ࡢᙧែ࡟ࡣ⾑୰ P4 ⃰ᗘ࡛ࡣ࡞ࡃ㸪༸ᕢෆ࡛ࡢ㯤య࡜ࡢ఩⨨㛵ಀࡀ኱ࡁࡃ㛵
୚ࡍࡿࡇ࡜ࡀ♧၀ࡉࢀࡓࠋヨ㦂 2 ࡟࠾࠸࡚㸪᤼༸☜ㄆ᪥࠿ࡽ 5 ᪥┠ࡲ࡛ࡢ୺ᖍ༸⬊ࡢᖹ
ᆒ┤ᚄ࠾ࡼࡧ⾑୰ P4 ⃰ᗘ࡟ඹᏑ⩌࡜㠀ඹᏑ⩌࡜ࡢ㛫࡛ᕪࡣࡳࡽࢀ࡞࠿ࡗࡓࡀ㸪༸⬊ᾮ୰
ࡢ P4 ⃰ᗘࡀඹᏑ⩌࡛㧗࠸࡜࠸࠺⤖ᯝࡀᚓࡽࢀࡓࠋࡇࡢ⌧㇟ࡀ⏕ࡌࡓཎᅉ࡜ࡋ࡚㸪༸ᕢෆ
࡛ࡢ㏆㞄ࡢ㯤య࠿ࡽ⏘⏕ࡉࢀࡓ P4 ࡀ⾑⟶ࢆ㏻ࡌ࡚୺ᖍ༸⬊ࡢ༸⬊ቨẟ⣽⾑⟶࡟౵ධࡋ㸪
P4 ࡀ༸⬊ᾮෆ࡟ᾐ㏱ࡋࡓ࡜࠸࠺ྍ⬟ᛶࡶ⪃࠼ࡽࢀࡿࡀ㸪༸ᕢෆࡢ⾑⟶㉮⾜ࡸᙧᡂࡢ≧ἣ
ࡢゎ᫂ࡶྵࡵ࡚᭦࡞ࡿ◊✲ࢆ⾜ࡗ࡚࠸ࡃᚲせࡀ࠶ࡿ࡜⪃࠼ࡽࢀࡿࠋ
67
Table 3.1. Plasma P4 concentration on Day 6.
P4 (ng/ml)
IG
CG
P-value
2.7 㼼 0.3
3.5 㼼 0.3
P < 0.05
Values are mean 㼼 SEM.
IG; Ipsilateral group: Dominant follicle (DF) ipsilateral to the corpus luteum (CL).
CG; Contralateral group: DF contralateral to the CL.
Day0 = The day of the first follicular wave emergence.
68
Plasma P4 concentration (ng/ml)
7.0
R=0.23
P:NS
6.0
5.0
4.0
3.0
2.0
1.0
13
14
15
16
17
18
Diameter of the first wave dominant follicle (mm)
Fig. 3.1.
The linear relationship between plasma P4 concentration and
diameter of the first wave dominant follicle on Day 6. Day 0 = The
day of the first follicular wave emergence.
69
Plasma P4 concentration (ng/ml)
7.0
IG R=0.36 P:NS
CG R=0.12 P:NS
6.0
5.0
4.0
3.0
2.0
1.0
13
14
15
16
17
18
Diameter of the first wave dominant follicle (mm)
Fig. 3.2.
The linear relationship between plasma P4 concentration and
diameter of the first wave dominant follicle (DF) on Day6 in IG and
CG. Day0 = The day of the first follicular wave emergence. IG;
Ipsilateral group: DF ipsilateral to the corpus luteum (CL). CG;
Contralateral group: DF contralateral to the CL.
70
Table 3.2. Diameter of the first follicular wave dominant follicle on Day6.
Diameter (mm)
IG
CG
P-value
15.5 㼼 0.2
14.7 㼼 0.2
P < 0.01
Values are mean 㼼 SEM.
IG; Ipsilateral group: Dominant follicle (DF) ipsilateral to the corpus luteum (CL).
CG; Contralateral group: DF contralateral to the CL.
Day0 = The day of the first follicular wave emergence.
71
Diameter of dominant follicle (mm)
14
IG
CG
12
10
8
6
G : NS
4
D : P < 0.001
G,D : NS
2
0
Day0
Day1
Day2
Day3
Day4
Days from follicular wave emergence
Fig. 3.3.
Comparative changes of the first follicular wave dominant follicle (DF) of
IG and CG from Day 0 to 4. Day 0 = The day of the first follicular wave
emergence. Effect of group (G) (NS), day (D) (P < 0.01) and interaction
between group and day (G,D) (NS). IG; Ipsilateral group: DF ipsilateral to
the corpus luteum (CL). CG; Contralateral group: DF contralateral to the CL.
Values are mean r SEM of each point.
72
Cross-sectional area of corpus luteum (mm2)
300
IG
CG
250
200
150
G : NS
100
D : P < 0.001
50
0
G,D : NS
Day0
Day1
Day2
Day3
Day4
Days
wave
emergence
Daysfrom
fromfollicular
follicular
wave
emergence
Fig. 3.4.
Comparative changes of cross-sectional area of corpus luteum (CL) of IG
and CG from Day 0 to 4. Day 0 = The day of the first follicular wave
emergence. Effect of group (G) (NS), day (D) (P < 0.001) and interaction
between group and day (G,D) (NS). IG; Ipsilateral group: Dominant follicle
(DF) ipsilateral to the CL. CG; Contralateral group: DF contralateral to the
CL. Values are mean r SEM of each point.
73
Plasma P4 concentration (ng/ml)
3.0
2.5
2.0
IG
CG
1.5
1.0
G : NS
D : P < 0.001
G,D : NS
0.5
0
Day0
Day1
Day2
Day3
Day4
Days from follicular wave emergence
Fig. 3.5.
Comparative changes of plasma P4 concentration of IG and CG from Day
0 to 4. Day 0 = The day of the first follicular wave emergence. Effect of
group (G) (NS), day (D) (P<0.001) and interaction between group and day
(G,D) (NS). IG; Ipsilateral group: Dominant follicle (DF) ipsilateral to the
corpus luteum (CL). CG; Contralateral group: DF contralateral to the CL.
Values are mean r SEM of each point.
74
Table 3.3. Plasma E2 concentration on Day4.
E2 (pg/ml)
IG
CG
P-value
1.69 㼼 0.12
1.51 㼼 0.15
P < 0.1
Values are mean 㼼 SEM.
IG; Ipsilateral group: Dominant follicle (DF) ipsilateral to the corpus luteum (CL).
CG; Contralateral group: DF contralateral to the CL.
Day0 = The day of the first follicular wave emergence.
75
Table 3.4. Sex steroids concentration in follicular fluid on Day4.
IG
CG
P-value
P4 (ng/ml)
48.8 㼼 12.7
16.2 㼼 3.2
P < 0.05
E2 (ng/ml)
419.2 㼼 33.2
339.4 㼼 53.5
NS
A4 (ng/ml)
84.6 㼼 23.1
102.7 㼼 40.2
NS
Values are mean 㼼 SEM.
IG; Ipsilateral group: Dominant follicle (DF) ipsilateral to the corpus luteum (CL).
CG; Contralateral group: DF contralateral to the CL.
Day0 = The day of the first follicular wave emergence.
76
➨㸲❶
㯤య࡜ྠ୍༸ᕢෆ࡟Ꮡᅾࡍࡿ➨ 1 ༸⬊Ἴ୺ᖍ༸⬊㸦W1DF㸧
ࡢᛶ㉁࠾ࡼࡧཷ⫾ᛶ࡟ཬࡰࡍᙳ㡪
77
4㸫1㸬ᗎㄽ
➨ 3 ❶ࡼࡾ㸪W1DF ࡢⓎ⫱ไᚚ࡟༸ᕢෆ࡛ࡢ㯤య࡜ࡢඹᏑࡢ᭷↓ࡀ㔜せ࡛࠶ࡿࡇ࡜ࡀ
᫂ࡽ࠿࡜࡞ࡗࡓࠋࡑࡇ࡛㸪ᮏ❶࡛ࡣࡇࡢ⌧㇟ࡀἪங∵࡟࠾࠸࡚ࡶྠᵝ࡟㉳ࡇࡿ⌧㇟࡛࠶
ࡿࡢ࠿ࢆ᫂ࡽ࠿࡟ࡍࡿࡓࡵ࡟㸪W1DF ࡜㯤యࡢ఩⨨㛵ಀࡀ W1DF ࡟୚࠼ࡿᙳ㡪ࢆㄪ࡭
ࡓࠋࡇࢀࡲ࡛㸪㯤యࡀᏑᅾࡍࡿ༸ᕢ࡜ྠഃࡢᏊᐑゅ࡟࠾ࡅࡿᏊᐑෆ⭷ࡢ⤌⧊୰ P4 ⃰ᗘࡣ㸪
཯ᑐഃࡢᏊᐑゅ࡟࠾ࡅࡿᏊᐑෆ⭷࡟ẚ࡭㧗࠸ࡇ࡜ࡀሗ࿌ࡉࢀ࡚࠸ࡿ㸦20㸧
ࠋࡲࡓ㸪᤼༸๓
༸⬊ࡀᏑᅾࡍࡿ༸ᕢ࡜ྠഃࡢ༸⟶ෆ E2 ⃰ᗘࡣ㸪཯ᑐഃࡢࡶࡢ࡟ẚ㍑ࡋ࡚㧗࠸ࡇ࡜ࡀሗ࿌
ࡉࢀ࡚࠸ࡿ㸦99㸧
ࠋࡇࢀࡽࡢ஦ᐇ࠿ࡽ㸪༸ᕢ࡜ྠഃࡢᏊᐑゅ࡜ࡢ㛫࡟ࡣᐦ᥋࡞ᒁᡤࡢࡘ࡞
ࡀࡾࡀᏑᅾࡋ㸪Ꮚᐑࡀྠഃࡢ༸ᕢ࠿ࡽศἪࡉࢀࡿᛶࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥࡢᙳ㡪ࢆᙉࡃཷ
ࡅ࡚࠸ࡿྍ⬟ᛶࡀ♧၀ࡉࢀࡿࠋࡑࡇ࡛㸪ேᕤᤵ⢭ᚋࡢཷ⫾⋡࡟ࡘ࠸࡚㸪ඹᏑ⩌࡜㠀ඹᏑ
⩌࡜࡛ẚ㍑ࡋ㸪W1DF ࡜㯤య࡜ࡢ఩⨨㛵ಀࡀ࢘ࢩࡢ⦾Ṫ⏕⌮࡟୚࠼ࡿᙳ㡪ࢆㄪᰝࡋࡓࠋ
4㸫2㸬ヨ㦂 1㸸Ἢங∵࡟࠾ࡅࡿ W1DF ࡜㯤యࡢඹᏑ࠾ࡼࡧ㠀ඹᏑ㛵ಀࡀ W1DF ࡜㯤యࡢ
Ⓨ⫱ືែ࠾ࡼࡧ⾑୰ P4 ⃰ᗘ᥎⛣࡟ཬࡰࡍᙳ㡪
4㸫2㸫1㸬౪ヨື≀
ᖏᗈ␆⏘኱Ꮫ␆⏘ࣇ࢕࣮ࣝࢻ⛉Ꮫࢭࣥࢱ࣮࡟࡚㣫㣴ࡉࢀ࡚࠸ࡿ㸪⮫ᗋⓗ࡟೺ᗣ࡛Ⓨ᝟
࿘ᮇࡀṇᖖ࡞࣍ࣝࢫࢱ࢖ࣥ✀⤒⏘Ἢங∵㸦n㸻30㸪ᖹᆒ⏘ḟ㸸2.2 r 0.2㸪ᖹᆒศፔᚋ᪥ᩘ㸸
99.9s8.0㸪ᖹᆒ᪥ங㔞㸸37.6s1.6 kg㸧ࢆ⏝࠸ࡓࠋ౪ヨࡋࡓಶయࡣ㸪ศፔᚋ࡟௦ㅰᛶ⑌ᝈ
ࡸ⦾Ṫ㞀ᐖ࡛἞⒪Ṕࡢ࡞࠸ࡶࡢ࡛࠶ࡿࠋ
4㸫2㸫2㸬ᐇ㦂᪉ἲ
⮬↛Ⓨ᝟Ⓨぢᚋ㸪24 ᫬㛫ẖ࡟┤⭠᳨ᰝࡲࡓࡣ㉸㡢Ἴ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚᤼༸ࡢ☜ㄆ
ࢆ⾜ࡗࡓࠋ᤼༸☜ㄆ᪥ࢆ Day 0 ࡜ࡋࡓࠋDay 2㸪4㸪6㸪8 ࠾ࡼࡧ 10 ࡢ㛫࡟㉸㡢Ἴ⏬ീデ᩿
78
⿦⨨ࢆ⏝࠸࡚༸ᕢࡢほᐹࢆ⾜ࡗࡓࠋࡇࡢ᫬㸪୺ᖍ༸⬊ࡀ 2 ࡘ࠶ࡿಶయ㸪ࡲࡓࡣ୺ᖍ༸⬊
ࡀ☜ㄆࡉࢀ࡞࠸ಶయࡣヨ㦂ࡼࡾ㝖እࡋࡓࠋࡲࡓ㸪ྠࡌ᪥࡟ṇ୰ᑿ㟼⬦ࡼࡾ᥇⾑ࢆ⾜ࡗࡓࠋ
4㸫2㸫3㸬 ༸ᕢࡢほᐹ
W1DF ࡜㯤యࡢඹᏑࡲࡓࡣ㠀ඹᏑ㛵ಀࡢほᐹ࡟ࡣ㸪5.0MHz ࡢࣜࢽ࢔ࣉ࣮ࣟࣈࡀ௜ᒓ
ࡋࡓ⤒┤⭠㉸㡢Ἴ⏬ീデ᩿⿦⨨㸦HS̺101V㸪ᮏከ㟁Ꮚ㸪ឡ▱㸧ࢆ⏝࠸ࡓࠋ༸ᕢほᐹ᫬࡟
᭱኱┤ᚄࢆ᭷ࡍࡿ༸⬊ࢆ W1DF ࡜ࡋ㸪W1DF ࡀྠ୍༸ᕢෆ࡟㯤య࡜ඹᏑࡍࡿሙྜࢆඹᏑ
⩌㸪㯤యࡀᏑᅾࡍࡿ༸ᕢ࡜ࡣ཯ᑐഃࡢ༸ᕢ࡟Ꮡᅾࡍࡿሙྜࢆ㠀ඹᏑ⩌࡜ࡋࡓࠋ
4㸫2㸫4㸬 ༸⬊࠾ࡼࡧ㯤యᙧែࡢほᐹ
୺ᖍ༸⬊࠾ࡼࡧ㯤యࡢ᩿㠃✚ࡣ㸪5.0MHzࡢࣜࢽ࢔ࣉ࣮ࣟࣈࡀ௜ᒓࡋࡓ⤒┤⭠㉸㡢Ἴ⏬
ീデ᩿⿦⨨㸦HS̺101V㸪ᮏከ㟁Ꮚ㸪ឡ▱㸧ࢆ⏝࠸࡚ ᐃࡋࡓࠋࣉ࣮ࣟࣈࢆᡭᣦ࡜࡜ࡶ࡟
┤⭠ෆ࡟ᤄධࡋ㸪ᕥྑ୧ഃ༸ᕢࡢ᩿ᒙീࢆほᐹࡋ㸪୺ᖍ༸⬊࠾ࡼࡧ㯤యࡢ᩿ᒙ⏬ീࡀ᭱኱
࡟࡞ࡿࡼ࠺㟼Ṇ⏬ࢆグ㘓ࡋ㸪ࣃࢯࢥࣥୖ࡟㟼Ṇ⏬ࢆ⛣ືࡉࡏ㸪୺ᖍ༸⬊ࡣ㛗ᚄ࡜▷ᚄࡢᖹ
ᆒ್ࢆᖹᆒ┤ᚄ࡜ࡋ㸪ࢹ࣮ࢱ࡜ࡋ࡚⏝࠸ࡓࠋ㯤యࡢ᩿㠃✚ࡣ㸪㯤యࡢ᩿ᒙ⏬ീࡀ᭱኱࡟࡞
ࡿࡼ࠺㟼Ṇ⏬ࢆグ㘓ࡋ㸪ࣃࢯࢥࣥୖ࡟㟼Ṇ⏬ࢆ⛣ືࡉࡏ㸪㯤యࡢ㛗ᚄ࡜▷ᚄࡢᖹᆒ್࠿ࡽ
ᖹᆒ┤ᚄࢆ⟬ฟࡋ㸪㸦ᖹᆒ┤ᚄ㸭2㸧2™3.14࡟ᙜ࡚ࡣࡵ㯤య᩿㠃✚ࢆ⟬ฟࡋ㸪ࢹ࣮ࢱ࡟⏝
࠸ࡓࠋ
4㸫2㸫5㸬᥇⾑
21G᥇⾑㔪࡜࣊ࣃࣜࣥຍ┿✵᥇⾑⟶㸦࣋ࣀࢪ࢙ࢡࢺϩ┿✵᥇⾑⟶㸪TERUMO㸪ᮾி㸧ࢆ
⏝࠸࡚ᑿ㟼⬦ࡼࡾ10mlࡢ᥇⾑ࢆ⾜ࡗࡓࠋ᥇ྲྀࡋࡓ⾑ᾮࡣịỈ୰࡟࡚ᛴ෭ᚋ㸪4Υ࡛2,000 g㸪
20ศ㛫㐲ᚰࡋ㸪⾑₢ศ㞳ᚋ㸪⾑୰P4⃰ᗘ ᐃࡲ࡛㸫30Υ࡟࡚෾⤖ಖᏑࡋࡓࠋ
79
4㸫2㸫6㸬⾑୰P4⃰ᗘࡢ ᐃ
Day 2㸪4㸪6㸪8࠾ࡼࡧ10࡟࠾ࡅࡿ⾑୰P4⃰ᗘࡢ ᐃࡣEIAἲ࡟ࡼࡾ ᐃࡋࡓࠋ ᐃ᪉ἲ
ࡣ➨2❶࡜ྠᵝࡢ᪉ἲ࡛⾜ࡗࡓࠋ⾑୰P4ࡢ ᐃෆኚື࠾ࡼࡧ ᐃ㛫ኚືࡣࡑࢀࡒࢀ5.2㸣࠾
ࡼࡧ7.4%࡛࠶ࡗࡓࠋ
4㸫2㸫7㸬⤫ィฎ⌮
⤖ᯝࡣࡍ࡭࡚ᖹᆒsᶆ‽ㄗᕪ࡛♧ࡋࡓࠋ⾑୰ P4 ⃰ᗘ㸪୺ᖍ༸⬊ࡢᖹᆒ┤ᚄ࠾ࡼࡧ㯤య
᩿㠃✚ࡢ᥎⛣ࡢẚ㍑࡟ࡣ㸪2 ඖ㓄⨨ศᩓศᯒࢆ⾜࠸㸪඲యࡢኚ໬ࡢ᭷ពᛶࢆㄪ࡭㸪஺஫
స⏝ࡀ᭷ព࡛࠶ࡗࡓࡶࡢ࡟ᑐࡋ࡚㸪
Bartlet ᳨ᐃࢆ⾜࠸ศᩓࡢᆒ୍ᛶࢆ᳨ᐃࡋࡓᚋ㸪
Pos-hoc
᳨ᐃ࡜ࡋ࡚ Sheffe ࡢከ⩌ẚ㍑᳨ᐃࢆ⾜ࡗࡓࠋP < 0.05 ࡢሙྜࢆ᭷ពᕪ࠶ࡾ࡜ࡋࡓࠋ⤫ィ
ฎ⌮࡟ࡣ⤫ィฎ⌮ࢯࣇࢺ࡛࠶ࡿ StatView㸦Abacus Concepts㸪Inc.㸪Berkeley㸪CA㸪USA㸧
ࢆ⏝࠸ࡓࠋ
4㸫3㸬ヨ㦂 2㸸W1DF ࡜㯤యࡢඹᏑ࠾ࡼࡧ㠀ඹᏑ㛵ಀࡀேᕤᤵ⢭ᚋࡢཷ⫾⋡࡟ཬࡰࡍᙳ
㡪
4㸫3㸫1㸬౪ヨື≀
ᖏᗈ␆⏘኱Ꮫ␆⏘ࣇ࢕࣮ࣝࢻ⛉Ꮫࢭࣥࢱ࣮࡟࡚㣫㣴ࡉࢀ࡚࠸ࡿ㸪⮫ᗋⓗ࡟೺ᗣ࡛Ⓨ᝟
࿘ᮇࡀṇᖖ࡞࣍ࣝࢫࢱ࢖ࣥ✀⤒⏘Ἢங∵㸦153 㢌㸧࡜ᮍ⤒⏘∵㸦75 㢌㸧ࢆ⏝࠸ࡓࠋヨ㦂
ᮇ㛫ࡣ 2008 ᖺ 3 ᭶㹼2013 ᖺ 9 ᭶࡛࠶ࡿࠋ౪ヨࡋࡓಶయࡣ㸪ศፔᚋ࡟௦ㅰᛶ⑌ᝈࡸ⦾Ṫ
㞀ᐖ࡛἞⒪Ṕࡢ࠶ࡿಶయࢆ㝖࠸ࡓࠋゎᯒ࡟ࡣ㸪ᘏ࡭ 238 㢌ࡢἪங∵㹙ᖹᆒศፔᚋ᪥ᩘ㸸
119.8 r 5.2 ᪥㸪ᖹᆒ⏘ḟ㸸2.2 r 0.1㸪ᖹᆒἪங㔞㸸33.9 r 0.5 kg/᪥㸪ᖹᆒ࣎ࢹ࢕࣭ࢥࣥࢹ
80
࢕ࢩ࣭ࣙࣥࢫࢥ࢔㸦BCS㸧
㸸2.91 r 0.02㸪ᖹᆒయ㔜㸸637.4 r 4.6 kg; ᖹᆒ r ᶆ‽ㄗᕪ㹛࠾
ࡼࡧᘏ࡭ 112 㢌ࡢᮍ⤒⏘∵㸦ᖹᆒ᭶㱋㸸14.2 r 0.3 ࣨ᭶㱋㸪ᖹᆒయ㔜㸸440.6 r 5.0 kg)ࢆ౪
ヨࡋࡓࠋἪங∵࠾ࡼࡧᮍ⤒⏘∵ࡣࢥ࣮ࣥࢧ࢖࣮ࣞࢪ㸪ࢢࣛࢫࢧ࢖࣮ࣞࢪ㸪኱㇋⢑㸪ࢺ࢘
ࣔࣟࢥࢩ✐⢏࠾ࡼࡧ㓄ྜ㣫ᩱࢆΰྜࡋࡓ TMR ࢆ⤥୚ࡉࢀ࡚࠾ࡾ㸪⮬⏤㣧Ỉ࡛ࡁࡿࣇࣜ
࣮ࢫࢺ࣮ࣝ࡟࡚㣫㣴ࡉࢀ࡚࠸ࡓࠋࡲࡓ㸪Ἢங∵ࡣ 1 ᪥ 2 ᅇᦢஙࡉࢀ࡚࠸ࡓࠋேᕤᤵ⢭ࡣ㸪
Ἢங∵࡟࠾࠸࡚ࡣศፔᚋ 60 ᪥࠿ࡽ㸪ᮍ⤒⏘∵࡟࠾࠸࡚ࡣయ㔜ࡀ 350 ਻௨ୖ࡟࡞ࡗࡓ᫬Ⅼ
࠿ࡽ㛤ጞࡉࢀࡓࠋ
4㸫3㸫2㸬ᐇ㦂᪉ἲ
እ㒊Ⓨ᝟ᚩೃ㸪ࢸ࣮ࣝ࣌࢖ࣥࢺᾘኻࡢ᭷↓㸪⭐㙾᳨ᰝ࠾ࡼࡧ┤⭠᳨ᰝ࡟ࡼࡿ᤼༸๓༸
⬊ࡢᏑᅾࡸ㏥⾜㯤యࡢ☜ㄆ࡟ࡼࡿ⮬↛Ⓨ᝟Ⓨぢᚋ࡟ேᕤᤵ⢭ࢆᐇ᪋ࡋࡓࠋேᕤᤵ⢭ᐇ᪋
24 ᫬㛫ᚋ࡟┤⭠᳨ᰝࡲࡓࡣ㉸㡢Ἴ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚᤼༸ࡢ☜ㄆࢆ⾜ࡗࡓࠋ᤼༸ࡋ࡚
࠸࡞࠸ሙྜ㸪෌ᗘேᕤᤵ⢭ࢆᐇ᪋ࡋ㸪24 ᫬㛫ᚋ࡟෌ᗘ᤼༸☜ㄆࢆ⾜ࡗࡓࠋࡇࡢ᫬㸪2 ᅇ
ࡢேᕤᤵ⢭ᐇ᪋ᚋ࡟㸪᤼༸ࡋ࡚࠸࡞࠿ࡗࡓಶయࡣヨ㦂ࡼࡾ㝖እࡋࡓࠋ᤼༸☜ㄆ᪥ࢆ Day 0
࡜ࡋ㸪Day 4 ࠿ࡽ 8 ࡢ㛫࡟┤⭠᳨ᰝࢆ⾜࠸㸪W1DF ࠾ࡼࡧ㯤యࡢ఩⨨㛵ಀࢆ㉸㡢Ἴ⏬ീ
デ᩿⿦⨨ࢆ⏝࠸࡚☜ㄆࡋࡓࠋࡇࡢ᫬୺ᖍ༸⬊ࡀ 2 ࡘ࠶ࡿಶయ㸪ࡲࡓࡣ୺ᖍ༸⬊ࡀ☜ㄆࡉ
ࢀ࡞࠸ಶయࡣヨ㦂ࡼࡾ㝖እࡋࡓࠋேᕤᤵ⢭ᚋ 40 ᪥┠࡟㉸㡢Ἴ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚ዷፎ
デ᩿ࢆ⾜࠸㸪ཷ⫾⋡ࢆ⟬ฟࡋࡓࠋ
4㸫3㸫3㸬 ༸ᕢࡢほᐹ
W1DF ࡜㯤యࡢඹᏑ࣭㠀ඹᏑ㛵ಀࡢほᐹ࡟ࡣ㸪5.0MHz ࡢࣜࢽ࢔ࣉ࣮ࣟࣈࡀ௜ᒓࡋࡓ
⤒┤⭠㉸㡢Ἴ⏬ീデ᩿⿦⨨㸦HS̺101V㸪ᮏከ㟁Ꮚ㸪ឡ▱㸧ࢆ⏝࠸ࡓࠋ༸ᕢほᐹ᫬࡟᭱኱
┤ᚄࢆ᭷ࡍࡿ༸⬊ࢆ W1DF ࡜ࡋ㸪W1DF ࡀྠ୍༸ᕢෆ࡟㯤య࡜ඹᏑࡍࡿሙྜࢆඹᏑ⩌㸪
81
㯤యࡀᏑᅾࡍࡿ༸ᕢ࡜ࡣ཯ᑐഃࡢ༸ᕢ࡟Ꮡᅾࡍࡿሙྜࢆ㠀ඹᏑ⩌࡜ࡋࡓࠋ
4㸫3㸫4㸬ཷ⫾⋡ࡢ⟬ฟ
ேᕤᤵ⢭ࡋࡓᘏ࡭㢌ᩘ࡟ᑐࡍࡿ㸪ࡑࡢேᕤᤵ⢭࡛ዷፎࡋࡓ㢌ᩘࡢ๭ྜ࡜ࡋ࡚㸪ཷ⫾⋡
ࢆ⟬ฟࡋࡓࠋ
4㸫3㸫5㸬⤫ィฎ⌮
ཷ⫾⋡ࡢホ౯࡟ࡣȮ஧஌᳨ᐃ࠾ࡼࡧࣟࢪࢫࢸ࢕ࢵࢡᅇᖐศᯒࢆ⏝࠸ࡓࠋ඲࡚ࡢ࢘ࢩ࡟
ᑐࡍࡿཷ⫾⋡ࡢホ౯࡟ࡣȮ஧஌᳨ᐃࢆ⏝࠸ࡓࠋ⤒⏘Ἢங∵࡜ᮍ⤒⏘∵ࡢཷ⫾⋡࡟ཬࡰࡍ
ᙳ㡪ࢆヲ⣽࡟ホ౯ࡍࡿࡓࡵ࡟㸪ࣟࢪࢫࢸ࢕ࢵࢡᅇᖐศᯒࢆ⏝࠸ࡓࠋ⤒⏘∵࡜ᮍ⤒⏘∵࡜
ࡶ࡟ཷ⫾⋡ࢆᚑᒓኚᩘ࡜ࡋࡓࠋ⤒⏘∵࡜ᮍ⤒⏘∵࡟ඹ㏻ࡢ⊂❧ኚᩘ࡟ࡣ㸪ྠ୍༸ᕢෆ࡛
ࡢ㯤య࡜ W1DF ࡢඹᏑࡢ᭷↓㸦ඹᏑ㸪㠀ඹᏑ㸧
㸪Ꮨ⠇㸦 ᬮ㸸6㹼9 ᭶㸪෭ᾴ㸸10㹼5 ᭶㸧
࡛࠶ࡿࠋຍ࠼࡚㸪ᮍ⤒⏘∵࡛ࡣయ㔜㸦㸺441kg㸪Ӎ441kg㸧ࢆ⊂❧ኚᩘ࡜ࡋ࡚㸪ࣟࢪࢫࢸ
࢕ࢵࢡᅇᖐศᯒࢆ⾜ࡗࡓࠋ⤒⏘Ἢங∵࡛ࡣศፔᚋ᪥ᩘ㸦㸺120 ᪥㸪Ӎ120 ᪥㸧
㸪Ἢங㔞㸦㸺
34kg/᪥㸪Ӎ34kg/᪥㸧
㸪⏘ḟ㸦1㸪2㸪Ӎ3㸧
㸪࣎ࢹ࢕࣭ࢥࣥࢹ࢕ࢩ࣭ࣙࣥࢫࢥ࢔㸦BCS㸹㸺3㸪
Ӎ3㸧
㸦27㸧࠾ࡼࡧయ㔜㸦㸺637kg㸪Ӎ637kg㸧ࢆ⊂❧ኚᩘ࡟㏣ຍࡋ࡚ࣟࢪࢫࢸ࢕ࢵࢡᅇᖐ
ศᯒࢆ⾜ࡗࡓࠋἪங㔞ࡣ᭶ 1 ᅇ⾜ࢃࢀࡿ∵⩌᳨ᐃࡢࢹ࣮ࢱࢆ౑⏝ࡋ㸪BCS ࠾ࡼࡧయ㔜ࡣ
␆⏘ࣇ࢕࣮ࣝࢻ⛉Ꮫࢭࣥࢱ࣮࡛ẖ᭶⾜ࢃࢀࡿ ᐃ࡛ᚓࡽࢀࡓࡶࡢࡢ࠺ࡕ㸪ேᕤᤵ⢭࠿ࡽ
┤㏆࡛ᚓࡽࢀࡓࢹ࣮ࢱࢆ౑⏝ࡋࡓࠋἪங㔞㸪BCS ࠾ࡼࡧయ㔜ࡣṇつศᕸ࡟ᚑࡗ࡚࠸ࡓࡓ
ࡵ㸪ᖹᆒ್࡛ 2 ⩌࡟ศࡅࢡࣛࢫศࡅࢆ⾜ࡗࡓࠋP < 0.05 ࢆ᭷ពᕪ࠶ࡾ࡜ࡋࡓࠋ඲࡚ࡢ᳨
ᐃ࡟ࡣ R ࢯࣇࢺ࢙࢘࢔㸦version 2.14.0 for Mac OS X.㸧ࢆ⏝࠸ࡓࠋ
4㸫4㸬⤖ᯝ
82
4㸫4㸫1㸬ヨ㦂 1 ⤖ᯝ
ᮏヨ㦂࡛ඹᏑ⩌ࡣ n㸻16㸦ᖹᆒศፔᚋ᪥ᩘ㸸104.8s10.5㸪ᖹᆒ⏘ḟ㸸1.9s0.2㸪ᖹᆒἪ
ங㔞㸸35.5s2.1 kg/᪥㸧
㸪㠀ඹᏑ⩌ࡣ n㸻14㸦ᖹᆒศፔᚋ᪥ᩘ㸸94.4s12.4㸪ᖹᆒ⏘ḟ㸸2.6
s0.4㸪ᖹᆒἪங㔞㸸39.9s2.3 kg/᪥㸧࡛࠶ࡗࡓࠋ㯤యࡢ᩿㠃✚ࡢ᥎⛣ࢆ Fig. 4.1.࡟♧ࡋࡓࠋ
ඹᏑ⩌࡜㠀ඹᏑ⩌㛫࡛㯤య᩿㠃✚ࡢ᥎⛣࡟ᕪࡣ࡞࠿ࡗࡓࠋ୺ᖍ༸⬊ࡢᖹᆒ┤ᚄࡢ᥎⛣ࢆ
Fig. 4.2.࡟♧ࡋࡓࠋDay 8 ࡛ඹᏑ⩌ࡣ㠀ඹᏑ⩌࡟ẚ㍑ࡋ࡚᭷ព࡟኱ࡁࡃⓎ⫱ࡋ࡚࠸ࡓࠋࡲ
ࡓ㸪ࡑࢀࡒࢀࡢ⩌ෆ࡛ࡢ᥎⛣ࢆẚ㍑ࡋࡓ࡜ࡇࢁ㸪ඹᏑ⩌࡛ࡣ Day 4 ࠿ࡽ 6 ࠾ࡼࡧ 8 ࡟࠿
ࡅ࡚᭷ព࡟኱ࡁࡃⓎ⫱ࡋࡓࡀ㸪㠀ඹᏑ⩌࡛ࡣ Day 4 ࠿ࡽ 8 ࡟࠿ࡅ࡚ࡣࡌࡵ࡚᭷ព࡟኱ࡁ
ࡃⓎ⫱ࡋࡓࠋඹᏑ⩌࡜㠀ඹᏑ⩌࡛⾑୰ P4 ⃰ᗘࡢ᥎⛣ࢆẚ㍑ࡋࡓ࡜ࡇࢁ㸪ᕪࡣࡳࡽࢀ࡞࠿
ࡗࡓ㸦Fig. 4.3㸧
ࠋ
4㸫4㸫2㸬ヨ㦂 2 ⤖ᯝ
ᮏヨ㦂࡛㸪౪ヨ∵඲࡚ࡢ⥲ཷ⫾⋡ࡣ 54.0㸣㸦189/350㸧
㸪⤒⏘∵࡛ࡢ⥲ཷ⫾⋡ࡣ 48.9㸣
㸦122/238㸧
㸪ᮍ⤒⏘∵࡛ࡢ⥲ཷ⫾⋡ࡣ 58.9㸣㸦67/112㸧࡛࠶ࡗࡓࠋ
ᮏヨ㦂࡛⤒⏘∵࡜ᮍ⤒⏘∵ࢆྜࢃࡏࡓ࡜ࡁࡢඹᏑ⩌ࡣ n㸻184㸪㠀ඹᏑ⩌ࡣ n㸻166 ࡛
࠶ࡗࡓࠋ⤒⏘∵࡟࠾ࡅࡿඹᏑ⩌ࡣ n㸻129㸦ᖹᆒศፔᚋ᪥ᩘ㸸115.4s5.7㸪ᖹᆒ⏘ḟ㸸2.4
s0.1㸪ᖹᆒἪங㔞㸸34.9s0.7 kg/᪥㸪ᖹᆒయ㔜㸸646.7s6.3 kg㸪ᖹᆒ BCS㸸2.91s0.03㸧
㸪
㠀ඹᏑ⩌ࡣ n㸻109㸦ᖹᆒศፔᚋ᪥ᩘ㸸118.3s5.6㸪ᖹᆒ⏘ḟ㸸2.1s0.1㸪ᖹᆒἪங㔞㸸32.7
s0.7 kg/᪥㸪ᖹᆒయ㔜㸸626.6s6.5 kg㸪ᖹᆒ BCS㸸2.92s0.03㸧࡛࠶ࡾ㸪ᮍ⤒⏘∵࡟࠾ࡅ
ࡿඹᏑ⩌ࡣ n㸻55㸦ᖹᆒయ㔜㸸434.1s6.3 kg㸪ᖹᆒ᭶㱋㸸14.1s0.6㸧
㸪㠀ඹᏑ⩌࡛ࡣ n㸻
57㸦ᖹᆒయ㔜㸸446.9s8.0 kg㸪ᖹᆒ᭶㱋㸸14.2s0.5㸧࡛࠶ࡗࡓࠋ
⤒⏘∵࠾ࡼࡧᮍ⤒⏘∵ࢆྜࢃࡏ㸪ඹᏑ⩌࡜㠀ඹᏑ⩌࡛ཷ⫾⋡ࢆẚ㍑ࡋࡓ࡜ࡇࢁ㸪ඹᏑ⩌
࡛᭷ព࡟ప࠸ཷ⫾⋡࡛࠶ࡗࡓ㹙ඹᏑ⩌ vs. 㠀ඹᏑ⩌㸻40.2㸣㸦74/184㸧 vs. 69.3㸣
㸦115/166㸧
㸹Fig. 4.4.㹛
ࠋࡲࡓ㸪⤒⏘∵࡜ᮍ⤒⏘∵࡛ࡑࢀࡒࢀඹᏑ⩌࡜㠀ඹᏑ⩌ࡢཷ⫾⋡ࢆ
83
ẚ㍑ࡋࡓ࡜ࡇࢁ㸪⤒⏘∵࡜ᮍ⤒⏘∵࡜ࡶ࡟ඹᏑ⩌࡛ప࠸ཷ⫾⋡࡛࠶ࡗࡓ㹙⤒⏘∵㸹ඹᏑ⩌
vs. 㠀ඹᏑ⩌㸻38.0㸣㸦49/129㸧 vs. 67.0㸣㸦73/109㸧
㸪ᮍ⤒⏘∵㸹ඹᏑ⩌ vs. 㠀ඹᏑ⩌㸻45.5㸣
㸦25/55㸧 vs. 73.7㸣㸦42/57㸧
㹛
ࠋࡲࡓ㸪ࣟࢪࢫࢸ࢕ࢵࢡᅇᖐศᯒࡢ⤖ᯝ࠿ࡽ㸪ᮏヨ㦂࡛ࡣ㸪
Ꮨ⠇㸪య㔜㸪ศፔᚋ᪥ᩘ㸪ங㔞㸪BCS࠾ࡼࡧ⏘ḟࡣཷ⫾⋡࡟ᙳ㡪ࢆཬࡰࡉ࡞࠸ࡇ࡜ࡀ᫂ࡽ
࠿࡜࡞ࡗࡓࠋ
4㸫5㸬⪃ᐹ
ヨ㦂 1 ࡟࠾࠸࡚⤒⏘Ἢங∵ࢆ⏝࠸࡚㸪W1DF ࡜㯤యࡀྠ୍༸ᕢෆ࡟ᏑᅾࡍࡿඹᏑ㛵ಀ
ࡢሙྜ࡜㸪ࡑࢀࡒࢀࡀᕥྑࡢ␗࡞ࡿ༸ᕢ࡟Ꮡᅾࡍࡿ㠀ඹᏑ㛵ಀࡢሙྜ࡟ࡘ࠸࡚ W1DF ࡜
㯤యࡢⓎ⫱ືែ࠾ࡼࡧ⾑୰ P4 ⃰ᗘ᥎⛣ࢆẚ㍑ࡋࡓࠋࡑࡢ⤖ᯝ㸪㯤యࡢⓎ⫱ືែ࡜⾑୰
P4 ⃰ᗘືែ࡟ᕪࡣࡳࡽࢀ࡞࠿ࡗࡓࡀ㸪ඹᏑ⩌ࡢ W1DF ࡣ኱ࡁࡃⓎ⫱ࡍࡿࡇ࡜ࡀ᫂ࡽ࠿࡜
࡞ࡗࡓࠋࡲࡓ㸪⤒⏘Ἢங∵࠾ࡼࡧᮍ⤒⏘∵ࢆ⏝࠸࡚㸪ேᕤᤵ⢭ᚋࡢཷ⫾⋡ࢆඹᏑ⩌࡜㠀
ඹᏑ⩌࡛ẚ㍑ࡋࡓ࡜ࡇࢁ㸪ඹᏑ⩌࡛పୗࡍࡿࡇ࡜ࢆ᫂ࡽ࠿࡟ࡋࡓࠋ
➨ 3 ❶࡛ࡣ㸪㠀Ἢங∵ࢆ⏝࠸࡚ Day 6 ࡟࠾ࡅࡿ W1DF ࡢᖹᆒ┤ᚄ࡜⾑୰ P4 ⃰ᗘ࡟ࡘ࠸
࡚ඹᏑ⩌࡜㠀ඹᏑ⩌࡛ẚ㍑ࡋࡓ࡜ࡇࢁ㸪ඹᏑ⩌࡛ᖹᆒ┤ᚄࡣ኱ࡁࡃ㸪⾑୰ P4 ⃰ᗘࡣప࠸
W1DF
࡜࠸࠺⤖ᯝࢆᚓࡽࢀࡓࠋ
Ἢங∵ࢆ⏝࠸ࡓᮏヨ㦂࡛ࡣ⾑୰ P4 ⃰ᗘ࡟ᕪࡣ࡞࠿ࡗࡓࡀ㸪
ࡢᖹᆒ┤ᚄࡣඹᏑ⩌࡛኱ࡁࡃ࡞ࡾ㸪ᖹᆒ┤ᚄ࡟㛵ࡋ࡚ࡣྠᵝࡢ⤖ᯝࡀᚓࡽࢀࡓࠋࡉࡽ࡟㸪
㯤యࡢᖹᆒ┤ᚄ࡟ᕪࡣ࡞ࡃ㸪➨ 3 ❶ࡢヨ㦂 2 ࡜ྠᵝࡢ⤖ᯝࡀᚓࡽࢀࡓࠋࡇࢀࡲ࡛㸪㧗Ἢ
ங∵ࡢ⾑୰ P4 ⃰ᗘࡣᮍ⤒⏘∵࡟ẚ࡭࡚పࡃ࡞ࡿ㸦78㸧ࡇ࡜ࡀሗ࿌ࡉࢀ࡚࠸ࡿࡀ㸪୍᪉࡛㸪
㠀Ἢங∵࡜Ἢங∵ࡢⓎ᝟࿘ᮇ୰ࡢ⾑୰ P4 ⃰ᗘ᥎⛣ࢆẚ㍑ࡋࡓ࡜ࡇࢁ㸪Ἢங∵࡛㯤యᮇ୰
ᮇ࡟࠾࠸࡚㧗ࡃ᥎⛣ࡍࡿ㸦23㸧࡜࠸࠺ሗ࿌ࡶ࠶ࡾ㸪ࡇࡢࡇ࡜ࡣἪங∵ࡢங⏕⏘࡟క࠺⫢
⮚࡛ࡢࢫࢸࣟ࢖ࢻ௦ㅰࡢ㐪࠸㸦100㸧ࡸ᤼༸๓༸⬊ࡢࢧ࢖ࢬࡀ␗࡞ࡿࡇ࡜࡛ᙧᡂࡉࢀࡿ㯤
యࡢࢧ࢖ࢬࡀ኱ࡁࡃ࡞ࡿࡇ࡜㸦23㸪97㸧࡟⏤᮶ࡍࡿ࡜⪃࠼ࡽࢀ࡚࠸ࡿࠋᮏヨ㦂࡛ࡣඹᏑ
⩌㸪㠀ඹᏑ⩌࡜ࡶ࡟ᵝࠎ࡞ங㔞ࢆᣢࡗࡓἪங∵ࡀヨ㦂࡟౪ヨࡉࢀࡓࡓࡵ㸪⾑୰ P4 ⃰ᗘ࡟
84
㛵ࡋ࡚➨ 3 ❶ࡢヨ㦂 1 ࡜␗࡞ࡿ⤖ᯝࡀᚓࡽࢀࡓࡢ࡛ࡣ࡞࠸࠿࡜᥎ ࡉࢀࡿࠋࡋ࠿ࡋ㸪ୖ
グ࡛㏙࡭ࡓࡼ࠺࡟ᮏヨ㦂࡛ࡣ㸪ඹᏑ⩌࡜㠀ඹᏑ⩌㛫࡛⾑୰ P4 ⃰ᗘ࡟ᕪࡣ࡞࠸࡟ࡶ㛵ࢃࡽ
ࡎ W1DF ࡢᖹᆒ┤ᚄࡀඹᏑ⩌࡛኱ࡁࡃⓎ⫱ࡋࡓࠋ
ᮍ⤒⏘∵ࢆ⏝࠸ࡓヨ㦂࡟࠾࠸࡚㸪W1DF
ࡢࢧ࢖ࢬࡣ㯤య࡜ྠ୍༸ᕢෆ࡟ඹᏑࡍࡿሙྜ࡜ඹᏑࡋ࡞࠸ሙྜ࡛ᕪࡣ࡞࠸࡜࠸࠺ሗ࿌
㸦40㸧ࡀᏑᅾࡍࡿࠋࡋ࠿ࡋ㸪ඹᏑ⩌࡛኱ࡁࡃⓎ⫱ࡍࡿ㸦42㸧࡜࠸࠺ሗ࿌ࡶᏑᅾࡋ㸪ᮏヨ
㦂࡛ࡣᚋ⪅ࡢ⤖ᯝ࡜୍⮴ࡍࡿ⤖ᯝ࡜࡞ࡗࡓࠋ➨ 3 ❶ࡢヨ㦂 2 ࡛ࡣ㸪Day 4 ࡲ࡛ࡢ୺ᖍ༸
⬊ࡢᖹᆒ┤ᚄࡢ᥎⛣࡟ඹᏑ⩌࡜㠀ඹᏑ⩌࡛᭷ព࡞ᕪࡣ࡞࠸࡜࠸࠺⤖ᯝࡀ♧ࡉࢀ㸪ᮏヨ㦂
1 ࡛ᚓࡽࢀࡓ⤖ᯝ࡜▩┪ࡍࡿ⤖ᯝ࡛࠶ࡿࠋࡋ࠿ࡋᮏヨ㦂࡛ࡢ୺ᖍ༸⬊ࡢᖹᆒ┤ᚄࡢ᥎⛣
ࢆࡳࡿ࡜ Day 4 ࡲ࡛ࡣ୧⩌㛫࡛ᕪࡀ࡞࠸ࡇ࡜࠿ࡽ㸪➨ 3 ❶ࡢヨ㦂 2 ࡟࠾࠸࡚ࡶ Day 6 ௨
㝆࡟࠾࠸࡚ඹᏑ⩌࡛኱ࡁࡃⓎ⫱ࡋࡓྍ⬟ᛶࡀ⪃࠼ࡽࢀࡿࠋ஦ᐇ㸪➨ 3 ❶ࡢヨ㦂 1 ࡛ Day 8
࡟࠾࠸࡚ඹᏑ⩌࡛ࡢW1DF ࡢᖹᆒ┤ᚄࡀ኱ࡁ࠿ࡗࡓࡇ࡜࠿ࡽࡶࡇࡢ௬ㄝࡣ⿬௜ࡅࡽࢀࡿࠋ
ᮏヨ㦂࡛ࡣ㸪ඹᏑ⩌࡜㠀ඹᏑ⩌࡜ࡢ㛫࡛⾑୰ P4 ⃰ᗘ࡟ᕪࡣ࡞࠸࡟ࡶ㛵ࢃࡽࡎ㸪W1DF ࡢ
ᖹᆒ┤ᚄ࡟ᕪࡀ⏕ࡌࡓࡇ࡜࠿ࡽ㸪W1DF ࡢ┤ᚄࡢᕪ␗ࡣ⾑୰ P4 ⃰ᗘ࡛ࡣ࡞ࡃ㸪㯤య࡜ࡢ
఩⨨㛵ಀ࡟㉳ᅉࡍࡿࡇ࡜ࡀ᥎ ࡉࢀࡿࠋ࣮࢝ࣛࢻࣉࣛ⏬ീデ᩿⿦⨨ࢆ⏝࠸ࡓ㐣ཤࡢヨ㦂
࡛ࡣ㸪㯤య࡜ W1DF ࡀྠ୍༸ᕢෆ࡛Ⓨ⫱ࡋ࡚࠸ࡿሙྜ㸪༸ᕢࡢ⾑⟶᢬ᢠ್ࡀపࡃ㸪༸⬊
ቨ⾑ὶࡀ኱ࡁ࠸ࡇ࡜ࢆሗ࿌ࡋ࡚࠸ࡿ㸦42㸧
ࠋ༸⬊ቨ⾑ὶࡣ㸪㑅ᢤࡉࢀࡿ༸⬊ࡸ㛢㙐ࡋ࡚࠸
ࡃ༸⬊ࢆホ౯ࡍࡿᣦᶆ࡜ࡋ࡚⏝࠸ࡽࢀ࡚࠾ࡾ㸦2㸪42㸧
㸪ࡲࡓ㸪᤼༸๓༸⬊ࡢ༸⬊ቨ⾑ὶ
࡜㸪ࡑࡢᚋࡢཷ⫾ᛶ㸦84㸧ࡸయእཷ⢭ᚋࡢ⬇ࡢⓎ⫱⋡㸦86㸧࡟ࡣṇࡢ㛵ಀࡀᏑᅾࡍࡿࡇ
࡜࠿ࡽ㸪༸⬊ቨ⾑ὶࡣ༸⬊ࡢάຊࢆホ౯ࡍࡿᣦᶆ࡜ࡉࢀ࡚࠸ࡿࠋᮏヨ㦂࡟࠾࠸࡚ࡶ㸪ඹ
Ꮡ⩌ࡢ W1DF ࡢ༸⬊ቨ⾑ὶࡀ኱ࡁ࠿ࡗࡓࡇ࡜ࡀ᥎ ࡉࢀ㸪ඹᏑ⩌ࡢ W1DF ࡬㓟⣲㸪ᰤ㣴
ࡉࡽ࡟ࡣ࣍ࣝࣔࣥࡀࡼࡾከࡃ౪⤥ࡉࢀࡿ㸦109㸧ࡇ࡜࡛㸪Ⓨ⫱ࡀ኱ࡁࡃ࡞ࡗࡓ࡜᥎ᐹࡉࢀ
ࡿࠋࡇࡢࡇ࡜ࡣ㸪W1DF ࡢⓎ⫱ࡸᛶ㉁࡟ཬࡰࡍせᅉ࡜ࡋ࡚㸪㯤య࡜ྠ୍༸ᕢෆ࡛Ⓨ⫱ࡍ
ࡿ࠿ྰ࠿࡜࠸࠺఩⨨ⓗ≧ἣࡢᙳ㡪ࡀᏑᅾࡍࡿࡇ࡜ࢆ♧၀ࡋ࡚࠸ࡿࠋ
㐣ཤࡢሗ࿌࡟࠾࠸࡚㸪W1DF ࡢⓎ⫱ືែࡸࡑࢀ࡟క࠺࣍ࣝࣔࣥືែࡣヲ⣽࡟ㄪ࡭ࡽࢀ
85
࡚ࡁࡓࠋࡋ࠿ࡋ࡞ࡀࡽ㸪W1DF ࡀ⦾Ṫ⏕⌮㸪≉࡟ཷ⫾ᛶ࡟ཬࡰࡍᙳ㡪࡟㛵ࡋ࡚ࡣ༑ศ࡟
ㄪᰝࡉࢀ࡚ࡇ࡞࠿ࡗࡓࠋ➨ 3 ❶ࡢヨ㦂 1㸪2 ࠾ࡼࡧᮏ❶ࡢヨ㦂 1 ࠿ࡽ㸪W1DF ࡢᛶ㉁ࡣ㯤
య࡜ྠ୍༸ᕢෆ࡛ඹᏑࡍࡿ࠿ྰ࠿࡜࠸࠺ࡇ࡜࡛␗࡞ࡿࡇ࡜ࡀ᥎ ࡉࢀࡿࠋࡇࢀࡲ࡛㸪㯤
యࡀᏑᅾࡍࡿ༸ᕢ࡜ྠഃࡢᏊᐑゅ࡟࠾ࡅࡿᏊᐑෆ⭷࡛ࡣ㸪཯ᑐഃࡢᏊᐑゅ࡟࠾ࡅࡿᏊᐑ
ࠋࡲࡓ㸪᤼༸๓༸⬊ࡀᏑᅾ
ෆ⭷࡟ẚ࡭⤌⧊୰ P4 ⃰ᗘࡀ㧗࠸ࡇ࡜ࡀሗ࿌ࡉࢀ࡚࠸ࡿ㸦20㸧
ࡍࡿ༸ᕢ࡜ྠഃࡢ༸⟶ෆ E2 ⃰ᗘࡣ㸪཯ᑐഃࡢࡶࡢ࡟ẚ㍑ࡋ࡚㧗࠸ࡇ࡜ࡀሗ࿌ࡉࢀ࡚࠸ࡿ
㸦99㸧
ࠋ࢘ࢩ࡛ࡣ㸪㯤యࡀᙧᡂࡉࢀ࡚࠸ࡿഃ࡜ྠഃࡢᏊᐑゅ࡛╔ᗋ㸪ዷፎࡋࡸࡍ࠸ࡇ࡜ࡀ
▱ࡽࢀ࡚࠸ࡿ㸦91㸧
ࠋࡇࢀࡽࡢ஦ᐇ࠿ࡽ㸪༸ᕢ࡜ྠഃࡢᏊᐑゅ࡟ࡣᐦ᥋࡞ᒁᡤࡢࡘ࡞ࡀࡾ
ࡀᏑᅾࡍࡿࡇ࡜ࡀ♧၀ࡉࢀࡿࠋ
ࣈࢱࢆ⏝࠸ࡓሗ࿌࡟࠾࠸࡚㸪
༸⟶࡟ྥ࠿࠺⾑⟶ࡢ⾑୰ P4㸪
A4 ࠾ࡼࡧ E2 ⃰ᗘࡣᮎᲈ⾑୰ࡢ⃰ᗘ࡟ẚ㍑ࡋ࡚㧗࠸ࡇ࡜࠿ࡽ㸪
༸ᕢ㟼⬦࠿ࡽᏊᐑࡸ༸⟶࡬
⾑ᾮࢆ౪⤥ࡍࡿ⾑⟶࡟㐃⤖ࡋ࡚࠸ࡿ༸ᕢື⬦࡬ᛶࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥࡀᑐྥὶ஺᥮࡟ࡼ
ࡾ⛣⾜ࡋ࡚࠸ࡿࡇ࡜ࡀ᥎ ࡉࢀ࡚࠸ࡿ㸦47㸧
ࠋヨ㦂 2 ࡟࠾࠸࡚㸪ேᕤᤵ⢭ᚋࡢཷ⫾⋡ࡣ⤒
⏘∵࡜ᮍ⤒⏘∵ඹ࡟ඹᏑ⩌࡛పୗࡍࡿࡇ࡜ࢆ♧ࡋࡓࠋࡲࡓ㸪ங㔞㸪⏘ḟ㸪ศፔᚋ᪥ᩘ㸪
య㔜࡟㛵ࢃࡽࡎ㸪ඹᏑ⩌࡛ཷ⫾ᛶࡀప࠸ࡇ࡜࠿ࡽ㸪ཷ⫾ᛶࢆỴᐃࡍࡿᅉᏊ࡜ࡋ࡚ W1DF
࡜㯤య࡛ࡢ఩⨨㛵ಀࡀ኱ࡁࡃᙳ㡪ࢆ୚࠼࡚࠸ࡿྍ⬟ᛶࡀ⪃࠼ࡽࢀࡿࠋⓎ᝟࿘ᮇ୰ࡢ⾑୰
E2 ⃰ᗘࢆ ᐃࡋࡓ࡜ࡇࢁ㸪➨ 1 ༸⬊ἼࡀⓎ⫱ࡍࡿᮇ㛫࡟⾑୰ E2 ⃰ᗘࡀୖ᪼ࡍࡿࡇ࡜ࡀሗ
࿌ࡉࢀ࡚࠸ࡿࡇ࡜࠿ࡽ㸪W1DF ࡣ⾑୰ E2 ⃰ᗘࢆୖ᪼ࡉࡏࡿ࡟༑ศ࡞ E2 ࢆ⏘⏕ࡋ࡚࠸ࡿ
ࡇ࡜ࡀ࠺࠿ࡀ࠼ࡿ㸦79㸧
ࠋࡑࡢࡓࡵ㸪W1DF ࡀᏑᅾࡍࡿ༸ᕢ࡜ྠഃࡢ༸⟶ࡸᏊᐑゅ࡛ࡣ
E2 ⃰ᗘࡀ㧗ࡃ࡞ࡿ࡜᥎ ࡉࢀࡿࠋ࢘ࢩࡢ༸⟶ୖ⓶⣽⬊ࢆ⏝࠸ࡓ in vitro ࡢᐇ㦂࡟࠾࠸࡚㸪
E2 ࡣ࢚ࢫࢺࣟࢤࣥཷᐜయȘ࡜ P4 ཷᐜయࡢ mRNA Ⓨ⌧㔞ࢆୖ᪼ࡉࡏࡿ࡜࠸࠺ሗ࿌ࡀ࠶ࡿ
㸦96㸧
ࠋࡲࡓ㸪࢘ࢩࡢᏊᐑෆ⭷⣽⬊ࢆ⏝࠸ࡓ in vitro ࡢᐇ㦂࡟࠾࠸࡚㸪E2 ࡣ࢚ࢫࢺࣟࢤࣥ
ཷᐜయ࠾ࡼࡧ P4 ཷᐜయⓎ⌧ࢆୖ᪼ࡉࡏࡿ㸦102㸧
ࠋࡇࢀࡽࡢࡇ࡜࠿ࡽ㸪E2 ࡣ༸⟶ࡸᏊᐑෆ
⭷ࡢࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥཷᐜయࡢⓎ⌧ࢆไᚚࡍࡿࡇ࡜ࡀ♧၀ࡉࢀࡿࠋW1DF ࡀ㯤య࡜ඹ
Ꮡࡍࡿሙྜ㸪W1DF ࠿ࡽ⏘⏕㸪ᨺฟࡉࢀࡿ E2 ࡀཷ⢭༸ࡸ⬇ࡀᏑᅾࡍࡿྠഃࡢ༸⟶ࡸᏊᐑ
86
ゅ࡟ᑐࡋ࡚ᒁᡤⓗ࡟స⏝ࡋዷፎᡂ❧࡟㛵ࢃࡿᶵ⬟࡟ᙳ㡪ࢆ୚࠼ࡿࡇ࡜࡛㸪ዷፎᡂ❧࡟ᑐ
ࡋ࡚㈇ࡢᙳ㡪ࢆ୚࠼࡚࠸ࡿࡇ࡜ࡀ᥎ ࡉࢀࡿࠋࡲࡓ㸪ྠ୍༸ᕢෆ࡟Ꮡᅾࡍࡿ W1DF ࡀ㯤
య࡟ᑐࡋ࡚㸪㯤యᙧᡂࡸ P4 ⏘⏕⬟ࢆᢚไࡍࡿ㸪ࡲࡓࡣ㯤యࡢᏑ⥆ᮇ㛫ࢆ▷ࡃࡍࡿࡇ࡜࡛
ཷ⫾ᛶࡀపୗࡋ࡚࠸ࡿྍ⬟ᛶࡶ⪃࠼ࡽࢀࡿࠋࡋ࠿ࡋ㸪ᮏ❶ࡢヨ㦂 2 ࠿ࡽ㯤యⓎ⫱ືែࡸ
⾑୰ P4 ⃰ᗘ࡟ඹᏑ⩌࡜㠀ඹᏑ⩌࡛ᕪࡀࡳࡽࢀ࡞࠿ࡗࡓࡇ࡜࠿ࡽ㸪
ඹᏑࡍࡿ W1DF ࡟ࡼࡿ
㯤య࡬ࡢᢚไస⏝ࡢྍ⬟ᛶࡣప࠸࡜⪃࠼ࡽࢀࡿࠋ୍᪉㸪㠀Ἢங⤒⏘∵ࢆ⏝࠸ࡓ➨ 3 ❶ࡢ
ヨ㦂 1 ࡛ࡣඹᏑ⩌࡛⾑୰ P4 ⃰ᗘࡀప࠿ࡗࡓࡇ࡜ࡸ㸪ᮏヨ㦂࡟࠾࠸࡚ࡶⓎ᝟࿘ᮇ඲యࢆ㏻
ࡋ࡚ࡢ㯤యࡢᏑ⥆ᮇ㛫ࢆㄪᰝࡋ࡚࠸࡞࠸ࡓࡵ㸪௒ᚋ᭦࡞ࡿ◊✲ࢆ⾜࠺ᚲせࡀ࠶ࡿ࡜⪃࠼
ࡿࠋ
ᮏ❶࡛ࡣ㸪
W1DF ࡸ㯤యࡢⓎ⫱ືែ࠾ࡼࡧ⾑୰ P4 ⃰ᗘࢆẚ㍑ࡍࡿࡇ࡜࡛㸪
㯤య࡜ W1DF
࡜ࡀྠ୍༸ᕢෆ࡟ඹᏑࡲࡓࡣඹᏑࡋ࡞࠸࡜࠸࠺༸ᕢෆ࡛ࡢ఩⨨㛵ಀࡀ⤒⏘Ἢங∵࡟࠾ࡅ
ࡿ W1DF ࡢⓎ⫱࡟㛵ࢃࡿせᅉ࡜ࡋ࡚㔜せ࡛࠶ࡿࡇ࡜ࢆ♧ࡋࡓࠋࡉࡽ࡟㸪ࡑࡢ఩⨨㛵ಀࡀ
ཷ⫾ᛶ࡟ࡲ࡛኱ࡁࡃᙳ㡪ࢆཬࡰࡍࡇ࡜ࢆ᫂ࡽ࠿࡟ࡋ㸪W1DF ࡢᛶ㉁࠾ࡼࡧ⦾Ṫ⏕⌮࡟ཬ
ࡰࡍᙳ㡪ࢆ♧ࡋࡓࠋ
4㸫6㸬ᑠᣓ
ᮏ❶࡛ࡣ㸪⤒⏘Ἢங∵ࢆ⏝࠸࡚㸪W1DF ࡀ㯤య࡜ྠ୍༸ᕢෆ࡛ඹᏑࡋ࡚Ⓨ⫱ࡍࡿሙྜ㸪
W1DF ࡢᖹᆒ┤ᚄ᥎⛣ࡀ㠀ඹᏑ࡟ẚ࡭࡚኱ࡁࡃⓎ⫱ࡍࡿࡀ㸪㯤యࡢⓎ⫱ືែࡸ⾑୰ P4 ⃰
ᗘࡢ᥎⛣࡟㐪࠸ࡣࡳࡽࢀ࡞࠸ࡇ࡜ࢆ♧ࡋࡓࠋࡲࡓ㸪ேᕤᤵ⢭ᚋ࡟࠾ࡅࡿ W1DF ࡀ㯤య࡜
ඹᏑࡍࡿሙྜ࡜㠀ඹᏑࡢሙྜ࡛ࡢࡑࡢᚋࡢཷ⫾⋡ࢆẚ㍑ࡋࡓ࡜ࡇࢁ㸪ඹᏑ⩌࡛ཷ⫾⋡ࡀ
ప࠸ࡇ࡜ࢆ♧ࡋ㸪W1DF ࡢ⦾Ṫ⏕⌮࡟୚࠼ࡿᙳ㡪ࢆ᫂ࡽ࠿࡟ࡋࡓࠋ
87
Cross-sectional area of corpus luteum (mm2)
700
600
IG
CG
500
400
G : NS
D : P < 0.001
300
G,D : NS
200
100
Day2
Day4
Day6
Day8
Day10
Days from follicular wave emergence
Fig. 4.1.
Comparative changes of corpus luteum (CL) of IG and CG on Day 2, 4, 6, 8,
10. Day 0 = The day of the first follicular wave emergence. Effect of group (G)
(NS), day (D) (P < 0.001) and interaction between group and day (G,D) (NS).
IG; Ipsilateral group: Dominant follicle (DF) ipsilateral to the CL. CG;
Contralateral group: DF contralateral to the CL. Values are mean r SEM of
each point.
88
Diameter of dominant follicle (mm)
20
18
IG
CG
16
14
12
G : P < 0.01
10
D : P < 0.001
G,D : P < 0.01
8
6
Day2
Day4
Day6
Day8
Day10
Days from follicular wave emergence
Fig. 4.2.
Comparative changes of the first follicular wave dominant follicle (DF)
of IG and CG on Day 2, 4, 6, 8, 10. Day 0 = The day of the first
follicular wave emergence. Effect of group (G) (P < 0.01), day (D) (P <
0.001) and interaction between group and day (G,D) (P < 0.01). IG;
ipsilateral group: DF ipsilateral to the corpus luteum (CL). CG;
contralateral group: DF contralateral to the CL. The asterisk denotes
difference between each point, : P < 0.05. Values are mean r SEM of
each point.
89
Plasma P
concentration
of P4 (ng/ml)
Plasma
(ng/ml)
4 concentration
7.0
IG
CG
6.0
5.0
4.0
3.0
G : NS
2.0
D : P < 0.001
1.0
G,D : NS
0
Day2
Day4
Day6
Day8
Day10
Daysfrom
fromfollicular
follicular wave
wave emergence
Days
emergence
Fig. 4.3.
Comparative changes of plasma P4 concentration of IG and CG on
Day 2, 4, 6, 8, 10. Day 0 = The day of the first follicular wave
emergence. Effect of group (G) (NS), day (D) (P < 0.001) and
interaction between group and day (G,D) (NS). IG; ipsilateral group:
Dominant follicle (DF) ipsilateral to the corpus luteum (CL). CG;
contralateral group: DF contralateral to the CL. Values are mean r
SEM of each point.
90
IG
80
73.7%
(42/57)
67.0%
(73/109)
70
Conception rate (%)
CG
60
50
45.5%
(25/55)
38.0%
(49/129)
40
30
20
10
0
Lactating dairy cows
Dairy heifers
Figure 4.4.
Conception rates in IG and CG. Conception rates were
different between IG and CG in both lactating dairy cows
and dairy heifers. IG; ipsilateral group: Dominant follicle
(DF) ipsilateral
to
the
corpus
luteum
(CL).
CG;
contralateral group: DF contralateral to the CL. The asterisk
denotes difference between each point, : P < 0.01.
91
➨㸳❶
⥲ྜ⪃ᐹ
92
㏆ᖺࡢ␆⏘⌧ሙ࡟࠾ࡅࡿከ㢌໬࠾ࡼࡧங∵࡟࠾ࡅࡿ㧗Ἢங໬࡟క࠸㸪Ⓨ᝟Ⓨぢ⋡ࡢప
ୗ࠾ࡼࡧཷ⫾⋡పୗࡀၥ㢟࡜࡞ࡗ࡚࠸ࡿࠋࡇࡢၥ㢟࡟ᑐฎࡍࡿࡓࡵ࡟㸪ᐃ᫬ேᕤᤵ⢭ࣉ
ࣟࢢ࣒ࣛࡢ㛤Ⓨࢆ୰ᚰ࡜ࡍࡿ◊✲ࡀ┒ࢇ࡟⾜ࢃࢀ࡚࠸ࡿࡀ㸪⦾Ṫᡂ⦼ࡢྥୖࡣ༑ศ࡟㐩
ᡂ࡛ࡁ࡚࠸࡞࠸ࠋࡇࡢࡇ࡜ࡣ㸪࢘ࢩࡢཷ⫾࡟㛵ࢃࡿ⦾Ṫ⏕⌮࡟ᑐࡍࡿ⌮ゎࡀᮍࡔ୙༑ศ
࡛࠶ࡿࡇ࡜ࢆ♧ࡋ࡚࠸ࡿࠋࡑࡇ࡛㸪⚾ࡣ㸪ᮍࡔ᫂ࡽ࠿࡟ࡉࢀ࡚࠸࡞࠸࢘ࢩࡢ⦾Ṫ⏕⌮ࢆ
᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࢆ┠ⓗ࡟࢘ࢩࡢⓎ᝟࿘ᮇ୰࡟Ⓨ⫱ࡍࡿ༸⬊Ἴ㸪≉࡟㸪࡯࡜ࢇ࡝ࡀ᤼༸
ࡍࡿࡇ࡜࡞ࡃ㛢㙐ࡋ࡚ࡋࡲ࠺➨ 1 ༸⬊Ἴࡢ୺ᖍ༸⬊࡟╔┠ࡋࡓࠋ➨ 1 ༸⬊ἼࡣⓎ᝟⤊஢
ᚋࡢ᤼༸┤ᚋ࠿ࡽ༸ᕢෆ࡛」ᩘࡢᑠ༸⬊ࡢⓎ⫱ࡀ㛤ጞࡉࢀࡿࡇ࡜࡛Ⓨ⌧ࡋ㸪Ⓨ⫱㛤ጞ࠿
ࡽ 2㹼3 ᪥ᚋ࡟ࡑࡢ୰࠿ࡽ᭱኱ࡢ༸⬊ࡢࡳࡀ㑅ᢤࡉࢀ㸪୺ᖍ༸⬊࡜࡞ࡾ㸪ࡑࢀ௨እࡢ༸⬊
ࡣ඲࡚㛢㙐ࡋ࡚ࡋࡲ࠺ࠋࡇࡢ➨ 1 ༸⬊Ἴ୺ᖍ༸⬊㸦W1DF㸧࡟ࡘ࠸࡚㸪༸⬊ࡢⓎ⫱ືែ
ࡸ㑅ᢤࡢ࣓࢝ࢽࢬ࣒ࢆ᫂ࡽ࠿࡟ࡍࡿࡓࡵ࡟㸪࣍ࣝࣔࣥືែࢆྵࡵ࡚ࡇࢀࡲ࡛ከࡃࡢ◊✲
ࡀ⾜ࢃࢀ࡚ࡁࡓࡀ㸪W1DF ⮬యࡢᛶ㉁ࡢ≉ᚩࡸ⦾Ṫ⏕⌮࡟࠾ࡅࡿព⩏࡟ࡘ࠸࡚ࡣ࡯࡜ࢇ
࡝◊✲ࡀ⾜ࢃࢀ࡚ࡇ࡞࠿ࡗࡓࠋࡑࡇ࡛㸪ࡇࡢ W1DF ࡢᛶ㉁㸪Ⓨ⫱࡟㛵ࢃࡿせᅉ㸪ࡉࡽ࡟㸪
ཷ⫾࡟୚࠼ࡿᙳ㡪ࢆ᫂ࡽ࠿࡟ࡍࡿࡓࡵ࡟㸪୺ᖍ༸⬊ࡢⓎ⫱ືែ㸪༸⬊ቨ⾑ὶࡢ᥎⛣㸪᤼
༸┤๓ࡢ⾑୰ E2 ⃰ᗘ㸪᤼༸๓ᚋ࡟࠾ࡅࡿ༸⬊ᾮ୰ࡢ P4㸪E2 ࠾ࡼࡧ A4 ⃰ᗘ㸪᤼༸ᚋ࡟࠾
ࡅࡿ㯤యࡢⓎ⫱ືែ࠾ࡼࡧ⾑୰ P4 ⃰ᗘࡢ᥎⛣㸪㯤య࡜ࡢ఩⨨㛵ಀ㸪ࡑࡋ࡚ཷ⫾ᛶࢆホ౯
ࡋࡓࠋ
➨ 2 ❶࡛ࡣ㸪⤒⏘㠀Ἢங∵ࢆ⏝࠸࡚ W1DF ࡢ≉᭷ࡢᛶ㉁ࢆ᫂ࡽ࠿࡟ࡍࡿࡓࡵ㸪➨ 2 ༸
⬊Ἴ୺ᖍ༸⬊㸦W2DF㸧࡜ࡢẚ㍑ࢆ⾜ࡗࡓ㸦W1DF㸸n㸻7㸪W2DF㸸n㸻7㸧
ࠋヨ㦂 1 ࡛ࡣ㸪
Day 3 ࠿ࡽ 6㸦Day 0㸻༸⬊ἼⓎ⌧᪥㸧ࡲ࡛ࡢ୺ᖍ༸⬊ࡢⓎ⫱ືែ࡜⾑୰ P4 ⃰ᗘࡢ᥎⛣㸪
ࡑࡋ࡚ Day 6 ࡟࠾ࡅࡿ༸⬊ቨ⾑ὶࢆ࣮࢝ࣛࢻࣉࣛ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚ ᐃࡋࡓࠋࡑࡢ
⤖ᯝ㸪W1DF ࡣ W2DF ࡜ẚ㍑ࡋ࡚ᖹᆒ┤ᚄࡣ኱ࡁࡃ᥎⛣ࡋ㸪Day 6 ࡢᖹᆒ┤ᚄࡣ᭷ព࡟
኱ࡁ࠿ࡗࡓࠋ୺ᖍ༸⬊࡟࡞ࡗ࡚࠿ࡽࡢⓎ⫱⋡ࡀ W1DF ࡛኱ࡁ࠸ࡇ࡜ࡀ㸪ᖹᆒ┤ᚄࡢᕪ␗
ࢆࡶࡓࡽࡋࡓཎᅉ࡛࠶ࡿ࡜⪃࠼ࡽࢀࡓࠋࡲࡓ㸪⾑୰ P4 ⃰ᗘ᥎⛣ࢆ୧⩌㛫࡛ẚ㍑ࡋࡓ࡜ࡇ
93
ࢁ㸪W1DF ࡀⓎ⫱ࡍࡿᮇ㛫ࡢ⾑୰ P4 ⃰ᗘࡣ㸪W2DF ࡀⓎ⫱ࡍࡿᮇ㛫ࡢ⾑୰ P4 ⃰ᗘࡼࡾ
పࡃ᥎⛣ࡍࡿࡇ࡜ࡀ♧ࡉࢀࡓࠋᮍ⤒⏘∵ࢆ⏝࠸ࡓヨ㦂࡟࠾࠸࡚㸪W1DF ࡀⓎ⫱ࡍࡿ᫬ᮇ
࡟⭐ෆ␃⨨ᆺ P4 〇๣ࢆᤄධࡋࡓ࡜ࡇࢁ㸪ᤄධࡋ࡞࠿ࡗࡓሙྜ࡟ẚ㍑ࡋ࡚୺ᖍ༸⬊ࡢ᭱኱
┤ᚄࡀᑠࡉࡃ࡞ࡾ㸪⾑୰ P4 ⃰ᗘࡀ㧗࠸᮲௳ୗ࡛ࡣ୺ᖍ༸⬊ࡢⓎ⫱ࡀᢚไࡉࢀࡿࡇ࡜ࡀ♧
ࡉࢀ࡚࠸ࡿࠋ୺ᖍ༸⬊࡟㑅ᢤࡉࢀ㸪Ⓨ⫱ࡀ⥔ᣢࡉࢀࡿࡓࡵ࡟ࡣ㢛⢏ᒙ⣽⬊࡛ LHr ࡢⓎ⌧
ࡀᚲ㡲࡛࠶ࡾ㸪୺ᖍ༸⬊ࡣ LH ౫Ꮡᛶ࡟Ⓨ⫱ࡍࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿࠋ⾑୰ P4 ⃰ᗘࡀప
࠸࡜㸪⬻ୗᆶయ๓ⴥ࠿ࡽศἪࡉࢀࡿ LH ࡢࣃࣝࢫ㢖ᗘࡀ㧗ࡃ࡞ࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠾ࡾ㸪
ᮏ◊✲࡟࠾࠸࡚ W1DF ࡢⓎ⫱ࡀ኱ࡁ࠸ࡢࡣ㧗࠸ LH ࣃࣝࢫ㢖ᗘ࡟㉳ᅉࡍࡿ࡜᥎ ࡉࢀࡿࠋ
ࡲࡓ㸪ᮏ◊✲࡛ࡣ༸⬊ቨ⾑ὶ࡟࠾࠸࡚㸪W1DF ࡛኱ࡁ࠸ࡇ࡜ࢆ♧ࡋࡓࠋ୺ᖍ༸⬊ࡀ㑅ᢤ
ࡉࢀࡿ๓ᚋ࡛༸⬊ቨ⾑ὶࡀቑຍࡍࡿࡇ࡜㸪㛢㙐ࡍࡿ༸⬊࡛ࡣ༸⬊ቨ⾑ὶࡀᾘኻࡍࡿࡇ࡜
࠿ࡽ㸪༸⬊ቨ⾑ὶࡣ༸⬊ࡢάຊࡢᣦᶆ࡜࡞ࡿࡓࡵ㸪W1DF ࡢάຊࡣ W2DF ࡟ẚ㍑ࡋ࡚㧗
࠸ࡇ࡜ࡀ᥎ ࡉࢀࡓࠋࡑࡇ࡛㸪ヨ㦂 2 ࡛ࡣ㸪PGF2α ࢆ Day 6㸪GnRH ࢆ Day 8 ࡟ᢞ୚ࡋ㸪
Ⓨ᝟࠾ࡼࡧ᤼༸ㄏ㉳ࢆ⾜࡞࠸㸪ࡑࢀ࡟క࠺ W1DF ࡜ W2DF ࡢᛶ㉁ࢆẚ㍑ࡋࡓࠋGnRH ᢞ
୚᫬㸦Day 8㸧ࡢ⾑୰ E2 ⃰ᗘࢆẚ㍑ࡋࡓ࡜ࡇࢁ㸪W1DF ࡛᭷ព࡟㧗࠿ࡗࡓࠋᖹᆒ┤ᚄࡣ
W1DF ࡛኱ࡁࡃ᥎⛣ࡋࡓࠋࡲࡓ㸪༸⬊ቨ⾑ὶࡢ᥎⛣࡟࠾࠸࡚ࡣ㸪GnRH ᢞ୚ᚋࡢ༸⬊ቨ
⾑ὶࡣ W1DF ࡛᭷ព࡟㧗࠿ࡗࡓࠋࡇࢀࡣ GnRH ᢞ୚๓ᚋ࡛ࡢ⾑ὶቑຍࡀ W1DF ࡛኱ࡁ
࠿ࡗࡓࡇ࡜ࡀཎᅉ࡛࠶ࡿ࡜⪃࠼ࡽࢀࡿࠋᐃ᫬ேᕤᤵ⢭ἲࡢ 1 ࡘ࡛࠶ࡿ࢜ࣈࢩࣥࢡࢆ⏝࠸
ࡓヨ㦂࡟࠾࠸࡚㸪GnRH ᢞ୚᫬ࡢ⾑୰ E2 ⃰ᗘ࡜ࡑࡢᚋࡢཷ⫾ྍ⬟ᛶ࡟ṇࡢ┦㛵㛵ಀࡀࡳ
ࡽࢀ࡚࠸ࡿࠋࡉࡽ࡟㸪GnRH ᢞ୚ 26 ᫬㛫ᚋࡢ༸⬊ቨ⾑ὶ࡜ேᕤᤵ⢭ᚋࡢཷ⫾ࡢ᭷↓࠾ࡼ
ࡧࡑࡢ᤼༸๓༸⬊࠿ࡽᚓࡽࢀࡿ༸Ꮚࡢయእཷ⢭ᚋࡢ⬇Ⓨ⫱ࢆẚ㍑ࡋࡓ◊✲࡛ࡣ㸪୙ཷ⫾
∵࡟ẚ㍑ࡋ࡚ཷ⫾∵ࡢ༸⬊ቨ⾑ὶࡀ㧗ࡃ㸪ࡉࡽ࡟⬇┙⬊࡟ࡲ࡛Ⓨ⫱ࡋࡓ༸Ꮚࢆ᭷ࡋࡓ༸
⬊࡛༸⬊ቨ⾑ὶࡀ㧗࠿ࡗࡓࠋࡋࡓࡀࡗ࡚㸪W1DF ࡣཷ⫾ᛶࡢ㧗࠸άຊࡢ࠶ࡿ༸⬊࡛࠶ࡿ
࡜᥎ ࡉࢀࡿࠋヨ㦂 3 ࡛ࡣ㸪W1DF ࡢᛶ㉁ࢆࡉࡽ࡟ヲ⣽࡟ホ౯ࡍࡿࡓࡵ࡟㸪GnRH ᢞ୚
๓㸦W1DF㸸n㸻7㸪W2DF㸸n㸻7㸧࡜ᢞ୚ 24 ᫬㛫ᚋ㸦W1DF㸸n㸻6㸪W2DF㸸n㸻6㸧ࡢ༸
94
⬊ᾮ୰ࡢᛶࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥ࡜㢛⢏ᒙ⣽⬊࡛Ⓨ⌧ࡍࡿ mRNA Ⓨ⌧㔞ࢆẚ㍑ࡋࡓࠋ
GnRH ᢞ୚๓ࡢ༸⬊࡟ࡘ࠸࡚ࡣ㸪ヨ㦂 2 ࡟࠾ࡅࡿ⾑୰ E2 ⃰ᗘࡢᕪ␗࡟㛵ࢃࡿ༸⬊ᶵ⬟ࢆ
ホ౯ࡍࡿࡓࡵ࡟㸪༸⬊ᾮ E2㸪A4 ࠾ࡼࡧ㢛⢏ᒙ⣽⬊࡛ࡢ CYP19A1 mRNA Ⓨ⌧㔞ࢆẚ㍑ࡋ
ࡓࠋࡉࡽ࡟㸪W1DF ࡟ࡳࡽࢀࡓ GnRH ᢞ୚ 24 ᫬㛫ᚋࡢ༸⬊ቨ⾑ὶࡢ㧗್ࡀ㸪LH ࢧ࣮ࢪ
࡟ᑐࡍࡿ཯ᛂᛶࡢᕪ␗࡟㉳ᅉࡍࡿࡢ࠿ࢆㄪ࡭ࡿࡓࡵ㸪㢛⢏ᒙ⣽⬊࡟࠾ࡅࡿ LHr mRNA Ⓨ
⌧㔞ࢆẚ㍑ࡋࡓࠋࡑࡢ⤖ᯝ㸪༸⬊ᾮ E2 ࠾ࡼࡧ A4 ⃰ᗘࡣ W1DF ࡛㧗࠸್ࢆ♧ࡋࡓࡀ㸪࢔
࣐ࣟࢱ࣮ࢮ㸦CYP19A1㸧ࡢ mRNA Ⓨ⌧㔞࡟᭷ព࡞ᕪࡣ࡞࠿ࡗࡓࠋA4 ࡣෆ༸⬊⭷⣽⬊࡛
⏘⏕ࡉࢀ㸪㢛⢏ᒙ⣽⬊࡛࢔࣐ࣟࢱ࣮ࢮ࡟ࡼࡾ E2 ࡬࡜ኚ᥮ࡉࢀࡿࠋ࢔࣐ࣟࢱ࣮ࢮάᛶ࡟ᕪ
␗ࡀ࡞࠿ࡗࡓࡇ࡜࠿ࡽ㸪
E2 ࡢᇶ㉁࡛࠶ࡿ A4 ࢆ⏘⏕ࡍࡿෆ༸⬊⭷⣽⬊ࡢᶵ⬟ࡀ㧗࠸ࡇ࡜ࡀ㸪
ᮏ◊✲࡛ࡢW1DF࡟࠾ࡅࡿGnRHᢞ୚᫬ࡢ㧗࠸⾑୰E2 ⃰ᗘࢆࡶࡓࡽࡋࡓ࡜᥎ ࡉࢀࡓࠋ
ࡲࡓ㸪LHr mRNA Ⓨ⌧㔞ࡣ W1DF ࡛᭷ព࡟㧗࠿ࡗࡓࠋ࢘ࢩࡢ㢛⢏ᒙ⣽⬊࡟࠾࠸࡚㸪LH
ࡣ LHr mRNA Ⓨ⌧㔞ࢆቑຍࡉࡏࡿ࡜ሗ࿌ࡉࢀ࡚࠸ࡿࠋW1DF ࡣప࠸⾑୰ P4 ⃰ᗘ᮲௳ୗ
࡛Ⓨ⫱ࡋ࡚࠸ࡿࡓࡵ㸪ẚ㍑ⓗ㧗࠸㢖ᗘࡢ LH ࣃࣝࢫ࡟ࡉࡽࡉࢀ࡚࠸ࡿࡇ࡜ࡀண᝿ࡉࢀ㸪
ࡇࡢࡇ࡜ࡀ㢛⢏ᒙ⣽⬊࡛ࡢ㧗࠸ LHr mRNA Ⓨ⌧㔞ࢆࡶࡓࡽࡋࡓ࡜⪃࠼ࡽࢀࡿࠋḟ࡟㸪
GnRH ᢞ୚ 24 ᫬㛫ᚋࡢ㢛⢏ᒙ⣽⬊࡛Ⓨ⌧ࡋ࡚࠸ࡿ mRNA ࢆẚ㍑ࡋࡓࠋLH ࢧ࣮ࢪ᭚㟢ᚋ
ࡢ༸⬊ෆ࡛ࡣ㸪㢛⢏ᒙ⣽⬊࠾ࡼࡧ༸⬊⭷⣽⬊ࡣ㯤య⣽⬊࡬࡜ᛴ㏿࡟ኚ໬ࡋ㸪E2 ⏘⏕࠿ࡽ
P4 ⏘⏕࡬࡜ᶵ⬟ࡀࢩࣇࢺࡋ࡚࠸ࡃࠋຍ࠼࡚㸪㯤యᙧᡂ࡟ࡣ⾑⟶ᙧᡂࡀ㔜せ࡛࠶ࡾ㸪VEGF
ࡸ FGF ࡣ⾑⟶ᙧᡂࡢ୰ᚰⓗ࡞ᙺ๭ࢆᢸࡗ࡚࠸ࡿࠋ ᤼༸๓༸⬊ࡸ㯤యᙧᡂ᫬࡟㸪ࡇࢀࡽ
ࡢ⾑⟶ᙧᡂ࡟㛵ࢃࡿᅉᏊࡢᶵ⬟ࢆ㜼ᐖࡍࡿ࡜ࡑࡢᚋ࡟ᙧᡂࡉࢀࡿ㯤యࡢࢧ࢖ࢬࡸᶵ⬟ࡀ
పୗࡍࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿࠋࡉࡽ࡟㸪༸⬊ෆ࡛ࡣ LH ࢧ࣮ࢪ᭚㟢ᚋ㸪PG 㢮㸦PGF2α㸪
PGE2 ➼㸧ࡢ⃰ᗘࡀୖ᪼ࡍࡿࡀ㸪ࡇࡢ᫬ PGE2 ྜᡂࢆ㜼ᐖࡍࡿ࡜༸⬊◚⿣ࡀ㜼ᐖࡉࢀࡿࡇ
࡜ࡀሗ࿌ࡉࢀ࡚࠸ࡿࠋ
ࡲࡓ㸪
⾑⟶ᣑᙇᅉᏊ࡛࠶ࡿ NO ࡢྜᡂ㓝⣲࡛࠶ࡿ iNOS ࠾ࡼࡧ eNOS
ࡣ༸⬊ෆ࡛Ⓨ⌧ࡋ࡚࠸ࡿࠋࡇࢀࡽࡢᅉᏊࢆẚ㍑ࡍࡿࡇ࡜࡛㸪LH ࢧ࣮ࢪ࡟ᑐࡍࡿ཯ᛂᛶ
ࡸ W1DF ࡛ࡢ༸⬊ቨ⾑ὶࡢ㧗್ࡢཎᅉ㸪ࡉࡽ࡟ࡣࡑࡢᚋ࡟ᙧᡂࡉࢀࡿ㯤యࡢᶵ⬟࡟୚࠼
95
ࡿᙳ㡪࡟ࡘ࠸࡚ホ౯࡛ࡁࡿ࡜⪃࠼ࡓࠋCOX-2㸪PGES ࠾ࡼࡧ PGFS mRNA Ⓨ⌧㔞࡟᭷ព
࡞ᕪࡣ࡞࠿ࡗࡓࠋ ࡇࡢࡇ࡜ࡣ㸪᤼༸㐣⛬࡟ᚲ㡲࡞ࡇࢀࡽࡢᅉᏊࡢⓎ⌧㔞࡟ཬࡰࡍ㸪LH
ࢧ࣮ࢪ࡟ᑐࡍࡿ཯ᛂᛶ࡟W1DF࡜W2DF࡜ࡢ㛫࡛ᕪ␗ࡣ࡞࠸ࡇ࡜ࢆ♧ࡋ࡚࠸ࡿ࡜⪃࠼ࡽ
ࢀ㸪ࡇࢀࡽࡢᅉᏊࡢⓎ⌧㔞ࡢ㐪࠸ࡀ༸⬊ቨ⾑ὶࡢᕪ␗ࢆࡶࡓࡽࡋࡓཎᅉ࡛࠶ࡿ࡜ࡣ⪃࠼
ࡽࢀ࡞࠸ࠋiNOS mRNA Ⓨ⌧㔞࡟୧⩌㛫࡛ᕪࡣ࡞࠿ࡗࡓࡀ㸪eNOS mRNA Ⓨ⌧㔞ࡣ W1DF
࡛㧗࠸ഴྥࢆ♧ࡋࡓࠋࡇࡢࡇ࡜࠿ࡽ㸪༸⬊ࡢ⾑⟶ᣑᙇస⏝࡟ W1DF ࡜ W2DF ࡜ࡢ㛫࡛ᕪ
ࡀ⏕ࡌ࡚࠸ࡿྍ⬟ᛶࡶ⪃࠼ࡽࢀࡿࠋࡋ࠿ࡋ࡞ࡀࡽ㸪༸⬊ቨࡢ⾑⟶ࡣෆ༸⬊⭷࡟Ꮡᅾࡋ࡚
࠾ࡾ㸪ෆ༸⬊⭷⣽⬊࡛Ⓨ⌧ࡋ࡚࠸ࡿ⾑⟶సືᛶᅉᏊࡸ⾑⟶⥙ศᕸࡢ⛬ᗘࢆホ౯ࡋ࡚࠸ࡃ
ᚲせࡀ࠶ࡿࠋP4 ྜᡂ࡟㛵ࢃࡿࢫࢸࣟ࢖ࢻྜᡂ㓝⣲࡛࠶ࡿ P450-scc ࡜ 3β-HSD mRNA Ⓨ⌧
㔞࠾ࡼࡧ VEGF164 mRNA Ⓨ⌧㔞ࡣ W1DF ࡛㧗࠿ࡗࡓࠋࡇࢀࡣ㸪᤼༸ᚋ࡟ᙧᡂࡉࢀࡿ㯤
యࡢ⾑⟶ᙧᡂ࠾ࡼࡧ㯤య⣽⬊ࡢ P4 ྜᡂ⬟ࡀ㧗ࡃ࡞ࡿྍ⬟ᛶࢆ♧ࡋ࡚࠸ࡿࠋࡇࢀࡽࡢࡇ࡜
࠿ࡽ㸪W1DF ࡢ LH ࢧ࣮ࢪ᭚㟢࡟క࠺㯤య໬࡬ࡢ཯ᛂᛶࡣ㧗࠸ࡇ࡜ࡀ♧၀ࡉࢀࡓࠋヨ㦂
4 ࡛ࡣ㸪W1DF ࡜ W2DF ࡢ᤼༸ᚋ࡟ᙧᡂࡉࢀࡿ㯤యࡢᙧែ࠾ࡼࡧᶵ⬟ࢆホ౯ࡋࡓ㸦W1DF
㯤య㸸n㸻6㸪W2DF 㯤య㸸n㸻6㸧
ࠋ㯤య᩿㠃✚㸪㯤య⾑ὶ࠾ࡼࡧ⾑୰ P4 ⃰ᗘࡣ W1DF ᤼
༸ᚋ࡟ᙧᡂࡉࢀࡿ㯤య࡛㧗࠿ࡗࡓࠋࡇࢀࡲ࡛㸪᤼༸๓༸⬊ࡀ኱ࡁ࠸࡜ࡑࡢᚋ࡟ᙧᡂࡉࢀ
ࡿ㯤యࡀ኱ࡁࡃ࡞ࡿࡇ࡜㸪㯤య୰ᮇ࡟࠾࠸࡚⾑୰ P4 ⃰ᗘࡣ㯤య┤ᚄࡢᙳ㡪ࢆཷࡅࡿࡇ࡜
ࡀሗ࿌ࡉࢀ࡚࠸ࡿࠋᮏヨ㦂࡛ࡣ㸪᤼༸๓ࡢ W1DF ࡢᖹᆒ┤ᚄࡀ W2DF ࡟ẚ࡭࡚኱ࡁ࠸ࡇ
࡜࠿ࡽ㸪W1DF ࡢ᤼༸ᚋ࡟ᙧᡂࡉࢀࡿ㯤యࡢ᩿㠃✚ࡀ኱ࡁࡃ࡞ࡾ㸪ࡑࡢ⤖ᯝ㸪⾑୰ P4 ⃰
ᗘࡀ㧗ࡃ࡞ࡗࡓ࡜⪃࠼ࡽࢀࡿࠋຍ࠼࡚㸪W1DF ࡢ᤼༸ᚋ࡟ᙧᡂࡉࢀࡿ㯤యࡣ㸪㯤యᙧᡂ
ึᮇ࡟࠾ࡅࡿ㯤యࡢ⾑ὶ㔞ࡀ኱ࡁ࠸ࡇ࡜࡛㸪㯤యᙧᡂࡀಁࡉࢀ㯤య᩿㠃✚ࡀ኱ࡁࡃ࡞ࡾ㸪
ࡉࡽ࡟⾑ᾮ౪⤥㔞ࡀ኱ࡁ࠸ࡇ࡜࡛㯤య⣽⬊ࡢ P4 ྜᡂ⬟࠾ࡼࡧ㯤య࠿ࡽ⾑୰࡬ࡢ P4 ᨺฟ
ࡢஹ㐍ࡀ⏕ࡌ㸪⾑୰ P4 ⃰ᗘࡀ㧗ࡃ᥎⛣ࡋࡓྍ⬟ᛶࡶ⪃࠼ࡽࢀࡿࠋࡇࢀࡽࡢࡇ࡜࠿ࡽ㸪
W1DF ࡣ W2DF ࡜ẚ࡭࡚㸪༸⬊Ⓨ⫱࠾ࡼࡧ᤼༸๓ᚋࡢᶵ⬟ࡀ㧗࠸ࡇ࡜ࡀ᥎ ࡉࢀ㸪ࡑࢀ
ࡣ᤼༸ᚋ࡟ᙧᡂࡉࢀࡿ㯤యࡢᶵ⬟࡟⮳ࡿࡲ࡛ᙳ㡪ࢆ୚࠼࡚࠸ࡿࡇ࡜ࡀ᫂ࡽ࠿࡟࡞ࡗࡓࠋ
96
➨ 3 ❶࡛ࡣ㸪⤒⏘㠀Ἢங∵ࢆ⏝࠸࡚ W1DF ࡢⓎ⫱ࡸᶵ⬟࡟ᙳ㡪ࢆ୚࠼ࡿせᅉ࡟ࡘ࠸࡚
ㄪ࡭ࡓࠋヨ㦂 1 ࡛ࡣ㸪ᘏ࡭ 44 㢌ࡢ࢘ࢩࢆ⏝࠸ࡓࠋࡲࡎ㸪Day 6 ࡢ୺ᖍ༸⬊ࡢᖹᆒ┤ᚄ࡜
⾑୰ P4 ⃰ᗘࡢ┦㛵㛵ಀࢆㄪ࡭ࡓࠋḟ࡟㸪୺ᖍ༸⬊ࡢⓎ⫱ࡀ༸ᕢෆࡢ㯤య࡟ࡼࡿᙳ㡪ࢆཷ
ࡅࡿྍ⬟ᛶࢆ⪃࠼㸪୺ᖍ༸⬊࡜㯤యࡀྠ୍༸ᕢෆ࡛Ⓨ⫱ࡍࡿඹᏑ⩌࡜཯ᑐഃࡢ༸ᕢ࡛Ⓨ
⫱ࡍࡿ㠀ඹᏑ⩌ࡢ 2 ࡘ࡟ศࡅ㸪ࡑࢀࡒࢀࡢ⩌࡛ࡢ୺ᖍ༸⬊ࡢᖹᆒ┤ᚄ࡜⾑୰ P4 ⃰ᗘࢆẚ
㍑ࡋࡓࠋࡑࡢ⤖ᯝ㸪Day 6 ࡢ୺ᖍ༸⬊ࡢᖹᆒ┤ᚄࡣ⾑୰ P4 ⃰ᗘ࡜ࡣ┦㛵㛵ಀࡀ࡞࠸ࡇ࡜
ࡀ♧ࡉࢀ㸪ࡇࢀࡣඹᏑ⩌࡜㠀ඹᏑ⩌࡟⩌ศࡅࡋࡓሙྜ࡛ࡶྠᵝࡢ⤖ᯝࡀᚓࡽࢀࡓࠋࡇࢀ
ࡽࡢࡇ࡜࠿ࡽ㸪Day 6 ࡢ⾑୰ P4 ⃰ᗘࡣ W1DF ࡢⓎ⫱࡟ᙳ㡪ࢆ୚࠼ࡿせᅉ࡛ࡣ࡞࠸ࡇ࡜ࡀ
᫂ࡽ࠿࡜࡞ࡗࡓࠋ୍᪉࡛㸪୺ᖍ༸⬊ࡢᖹᆒ┤ᚄࡣඹᏑ⩌࡛㠀ඹᏑ⩌࡟ẚ࡭᭷ព࡟኱ࡁ࠸
ࡇ࡜ࡀ♧ࡉࢀࡓࠋຍ࠼࡚㸪⾑୰ P4 ⃰ᗘࡣ㠀ඹᏑ⩌࡛㧗࠸್ࢆ♧ࡋࡓࠋヨ㦂 2 ࡛ࡣ㸪5 㢌
ࡢ⤒⏘㠀Ἢங∵ࢆ⏝࠸࡚㸪ඹᏑ⩌㸦n㸻5㸧࡜㠀ඹᏑ⩌㸦n㸻5㸧㛫࡛ࡢ୺ᖍ༸⬊ࡢᛶ㉁ࢆ
ẚ㍑ࡍࡿࡓࡵ㸪Day 0 ࠿ࡽ 4 ࡲ࡛ࡢ୺ᖍ༸⬊࡜㯤యࡢⓎ⫱ືែ㸪⾑୰ P4 ⃰ᗘ࠾ࡼࡧ Day 4
ࡢ⾑୰ E2 ࠾ࡼࡧ༸⬊ᾮ୰ᛶࢫࢸࣟ࢖ࢻ࣍ࣝࣔࣥ㸦E2㸪A4㸪P4㸧⃰ᗘࢆ ᐃࡋࡓࠋ୺ᖍ༸
⬊ࡢᖹᆒ┤ᚄࡣඹᏑ⩌࡛㧗ࡃ᥎⛣ࡋࡓࡀ᭷ពᕪࡣ࡞࠿ࡗࡓࠋ㯤యࡢᖹᆒ┤ᚄ࠾ࡼࡧ⾑୰
P4 ⃰ᗘ᥎⛣࡟ᕪࡣ࡞࠿ࡗࡓࠋ୺ᖍ༸⬊ࡢᖹᆒ┤ᚄ࡜⾑୰ P4 ⃰ᗘ᥎⛣࡟ᕪࡣ࡞ࡃヨ㦂 1 ࡜
␗࡞ࡿ⤖ᯝ࡛࠶ࡗࡓࠋ ࡇࢀࡣヨ㦂 1 ࡛ࡣ Day 6 ࡟୺ᖍ༸⬊ࡢᖹᆒ┤ᚄ࡜⾑୰ P4 ⃰ᗘࢆ
ᐃࡋࡓࡓࡵ㸪Ⓨ⫱ᮇ㛫ࡢ㐪࠸࡟ࡼࡿᙳ㡪ࡀ࠶ࡿ࡜⪃࠼ࡽࢀࡿࠋ⾑୰ E2 ⃰ᗘࡣඹᏑ⩌࡛
㧗࠸ഴྥࢆ♧ࡋࡓࡀ㸪༸⬊ᾮ୰ E2 ࠾ࡼࡧ A4 ⃰ᗘ࡟ᕪࡣ࡞࠿ࡗࡓࠋࡋ࠿ࡋ࡞ࡀࡽ㸪༸⬊
ᾮ୰ P4 ⃰ᗘࡣඹᏑ⩌࡛㧗࠿ࡗࡓࠋ㯤య࡜ྠ୍༸ᕢෆ࡛ඹᏑࡍࡿ W1DF ࡣ㸪༸ᕢෆ࡟༢⊂
࡛Ꮡᅾࡍࡿ W1DF ࡟ẚ࡭࡚㸪ᖹᆒ┤ᚄ㸪༸ᕢ࡬ࡢ⾑ὶ㔞࠾ࡼࡧ༸⬊ቨ⾑ὶ㠃✚ࡀ኱ࡁ࠸
ࡇ࡜ࡀሗ࿌ࡉࢀ࡚࠸ࡿࡇ࡜࠿ࡽ㸪ᮏヨ㦂࡟࠾࠸࡚ࡶඹᏑ⩌࡛ࡢ༸ᕢ࠾ࡼࡧ༸⬊࡬ࡢ⾑ὶ
㔞ࡀ኱ࡁ࠸ࡇ࡜ࡀ᥎ ࡉࢀ㸪㓟⣲㸪ᰤ㣴࠾ࡼࡧ࣍ࣝࣔࣥࡀࡼࡾ༸⬊࡬౪⤥ࡉࢀࡿࡇ࡜࡛
ᖹᆒ┤ᚄࡀ኱ࡁࡃ࡞ࡾ㸪༸⬊࡛⏘⏕ࡉࢀࡓ E2 ࡀࡼࡾ඲㌟ᚠ⎔୰࡟ᨺฟࡉࢀࡿࡇ࡜࡛⾑୰
E2 ⃰ᗘࡀ㧗ࡃ࡞ࡗࡓ࡜⪃࠼ࡽࢀࡿࠋ୍᪉㸪⾑୰ P4 ⃰ᗘࡀඹᏑ⩌࡛ప࠿ࡗࡓࡀ㸪⾑୰ P4
97
⃰ᗘ࡟ᕪࡀ⏕ࡌࡓཎᅉࡣᮏ◊✲࡛ࡣ᫂ࡽ࠿࡟࡛ࡁ࡞࠿ࡗࡓࠋ㯤యᶵ⬟ࡢホ౯ࡸඹᏑࡍࡿ
༸⬊ࡀ㯤యࡢᶵ⬟࡟ᙳ㡪ࢆ୚࠼࡚࠸ࡿྍ⬟ᛶࡶྵࡵ࡚㸪᭦࡞ࡿ◊✲ࢆ⾜࠺ᚲせࡀ࠶ࡿ࡜
⪃࠼ࡽࢀࡿࠋ༸⬊ᾮ୰ E2 ࠾ࡼࡧ A4 ⃰ᗘ࡟ᕪ␗ࡀ࡞࠿ࡗࡓࡇ࡜࠿ࡽ㸪ඹᏑ⩌࡜㠀ඹᏑࡢ
㛫࡛༸⬊ᶵ⬟࡟ᕪ␗ࡣ࡞࠸࡜⪃࠼ࡽࢀࡿࡓࡵ㸪༸⬊ᾮ P4 ⃰ᗘࡢᕪ␗ࡣ㏆㞄ࡢ㯤య࡛⏘⏕
ࡉࢀࡓ㧗⃰ᗘࡢ P4 ࡀ༸ᕢෆࡢ⾑⟶ࢆ௓ࡋ࡚୺ᖍ༸⬊࡟฿㐩ࡋ౵ධࡋࡓ࡜⪃࠼ࡽࢀࡿࠋࡋ
࠿ࡋ࡞ࡀࡽ㸪ࡇࡢⅬ࡟㛵ࡋ࡚ࡶ᥎ ࡢᇦࢆ㉺࠼࡞࠸ࡓࡵ㸪༸⬊ᶵ⬟ࡢᕪ␗ࡀᏑᅾࡍࡿྍ
⬟ᛶࡶྵࡵ᭦࡞ࡿ◊✲ࢆ⾜࠺ᚲせࡀ࠶ࡿ࡜⪃࠼ࡽࢀࡿࠋ➨ 3 ❶࡛ࡣ㸪W1DF ࡢᛶ㉁࡟ᙳ
㡪ࢆཬࡰࡍせᅉ࡜ࡋ࡚㸪ྠ୍༸ᕢෆ࡛㯤య࡜ඹᏑࡍࡿ࠿ྰ࠿࡜࠸࠺఩⨨㛵ಀࡢせᅉࡀ኱
ࡁ࠸ࡇ࡜ࡀ᫂ࡽ࠿࡟࡞ࡗࡓࠋ
➨ 4 ❶࡛ࡣ㸪➨ 3 ❶࡛᫂ࡽ࠿࡟࡞ࡗࡓ⌧㇟ࡀ㸪⤒⏘Ἢங∵࡟࠾࠸࡚ࡶほᐹࡉࢀࡿ⌧㇟
࡛࠶ࡿ࠿ㄪ࡭ࡓࠋࡲࡓ㸪㐣ཤࡢሗ࿌࠿ࡽ㸪㯤యࡀᏑᅾࡍࡿ༸ᕢ࡜ྠഃࡢᏊᐑゅࡢᏊᐑෆ
⭷࡛ࡢ⤌⧊୰ P4 ⃰ᗘࡣ཯ᑐഃࡢᏊᐑෆ⭷࡟ẚ㍑ࡋ࡚㧗࠸ࡇ࡜㸪᤼༸๓༸⬊ࡀᏑᅾࡍࡿഃ
ࡢ༸⟶ᾮ୰ࡢ E2 ⃰ᗘࡀ㧗࠸ࡇ࡜࠿ࡽ㸪༸ᕢ࡜ྠഃࡢᏊᐑゅ࡟ࡣᒁᡤⓗ࡞ࡘ࡞ࡀࡾࡀ࠶ࡿ
ࡇ࡜ࡀ⪃࠼ࡽࢀࡿࠋ࢘ࢩࡣ᤼༸ࡋࡓഃࡢᏊᐑゅ࡛㧗⋡࡟╔ᗋࡋዷፎ࡟⮳ࡿࡇ࡜ࡀ▱ࡽࢀ
࡚࠾ࡾ㸪ேᕤᤵ⢭ᚋࡢ W1DF ࡀ㯤య࡜ඹᏑࡋࡓሙྜ㸪ఱࡽ࠿ࡢᒁᡤⓗ࡞స⏝࡟ࡼࡾ㸪ࡑ
ࡢᚋࡢཷ⫾ᛶ࡟ᙳ㡪ࢆ୚࠼ࡿྍ⬟ᛶࡀ࠶ࡿࠋࡑࡢࡓࡵ㸪ேᕤᤵ⢭ᚋࡢ W1DF ࡜㯤యࡢ఩
⨨㛵ಀࢆㄪ࡭㸪ࡑࡢᚋࡢཷ⫾⋡ࢆẚ㍑ࡋࡓࠋヨ㦂 1 ࡛ࡣ㸪᤼༸☜ㄆ᪥ࢆ Day 0 ࡜ࡋ㸪Day
2㸪4㸪6㸪8 ࠾ࡼࡧ 10 ࡟୺ᖍ༸⬊࠾ࡼࡧ㯤యࡢᖹᆒ┤ᚄࢆィ ࡋ㸪ࡉࡽ࡟᥇⾑ࢆ⾜࠸⾑
୰ P4 ⃰ᗘࡢ ᐃࢆ⾜࠸㸪ඹᏑ⩌࡜㠀ඹᏑ⩌㛫࡛ẚ㍑ࡋࡓࠋ୺ᖍ༸⬊ࡢᖹᆒ┤ᚄࡣඹᏑ⩌
࡛ Day 6 ࠿ࡽ኱ࡁࡃ࡞ࡾ㸪Day 8 ࡟ࡣ㠀ඹᏑ࡟ẚ㍑ࡋ࡚᭷ព࡟኱ࡁࡃ࡞ࡗࡓࠋ㯤యࡢᖹᆒ
┤ᚄ࠾ࡼࡧ⾑୰ P4 ⃰ᗘࡢ᥎⛣ࡣ୧⩌㛫࡛ᕪࡣ࡞࠿ࡗࡓࠋ⾑୰ P4 ⃰ᗘ࡟ᕪࡀ࡞࠸࡟ࡶ㛵
ࢃࡽࡎ㸪ඹᏑ⩌࡛ࡢ୺ᖍ༸⬊ࡢᖹᆒ┤ᚄࡀ኱ࡁࡃ࡞ࡗࡓࡇ࡜࠿ࡽ㸪➨ 3 ❶࡛⪃ᐹࡋࡓࡼ
࠺࡟㸪㯤యࡀඹᏑࡍࡿ༸ᕢ࡛Ⓨ⫱ࡍࡿ୺ᖍ༸⬊ࡣ㸪༸ᕢ࡬ࡢ⾑ὶࡀ኱ࡁࡃ࡞ࡿࡇ࡜࡛㓟
⣲㸪ᰤ㣴࠾ࡼࡧ࣍ࣝࣔࣥ࡞࡝ࡀࡼࡾ౪⤥ࡉࢀࡿࡇ࡜࡛Ⓨ⫱ࡀಁࡉࢀࡓ࡜⪃࠼ࡽࢀࡿࠋヨ
98
㦂 2 ࡟࠾࠸࡚㸪ேᕤᤵ⢭ᚋࡢཷ⫾⋡ࡣ⤒⏘Ἢங∵࠾ࡼࡧᮍ⤒⏘∵࡜ࡶ࡟ඹᏑ⩌࡛పୗࡍ
ࡿࡇ࡜ࡀ᫂ࡽ࠿࡟࡞ࡗࡓࠋࡉࡽ࡟㸪ࡇࡢ⌧㇟ࡣ㸪Ꮨ⠇㸪ศፔᚋ᪥ᩘ㸪⏘ḟࡢᙳ㡪ࢆཷࡅ
࡞࠸ࡇ࡜ࡶ᫂ࡽ࠿࡟࡞ࡗࡓࠋࡇࡢ⌧㇟ࡣ㸪W1DF ࡀ⦾Ṫ⏕⌮࡟ᙳ㡪ࢆ୚࠼ࡿࡇ࡜ࢆ᫂ࡽ
࠿࡟ࡋࡓึࡵ࡚ࡢሗ࿌࡛࠶ࡿࠋ➨ 3 ❶ࡢヨ㦂 2 ࡟࠾࠸࡚㸪W1DF ࡣ༸⬊ෆ࡛༑ศ㔞ࡢ E2
ࢆ⏘⏕ࡋ⾑୰ E2 ⃰ᗘ࡟ᙳ㡪ࢆ୚࠼ࡿࡇ࡜ࢆ♧ࡋࡓࡀ㸪࢘ࢩ࡟࠾࠸࡚༸ᕢ࠿ࡽࡢ⾑⟶ࡀ༸
⟶࡜Ꮚᐑゅඛ➃࡟㐃⤖ࡋ࡚࠸ࡿࡇ࡜ࡀศ࠿ࡗ࡚࠾ࡾ㸪ྠഃࡢ༸⟶ࡸᏊᐑゅ࡟ᑐࡋ࡚ࡼࡾ
㧗⃰ᗘ࡛ᙳ㡪ࢆ୚࠼ࡿࡇ࡜ࡀ⪃࠼ࡽࢀࡿࠋࡲࡓ E2 ࡣᏊᐑෆ⭷⣽⬊࡟స⏝ࡋ࡚ E2 ࠾ࡼࡧ
P4 ཷᐜయⓎ⌧࡟ᙳ㡪ࢆ୚࠼ࡿࡇ࡜ࡀሗ࿌ࡉࢀ࡚࠸ࡿࡓࡵ㸪ཷ⢭༸ࡀᏑᅾࡍࡿ༸⟶ࡸᏊᐑ
ゅෆ⭷࡟ᑐࡋ࡚㧗⃰ᗘࡢ E2 ࡀస⏝ࡍࡿࡇ࡜࡛㸪⬇࡬ࡢⓎ⫱ࡸཷᐜ⬟࡟ᑐࡋ࡚ᙳ㡪ࢆ୚࠼
ࡿྍ⬟ᛶࡀ࠶ࡿࠋࡋ࠿ࡋ࡞ࡀࡽ㸪ᮏヨ㦂࡛ࡣཷ⫾ᛶ࡟ᕪ␗ࢆࡶࡓࡽࡍᶵᵓࡲ࡛ࢆ♧ࡍࡇ
࡜ࡣ࡛ࡁ࡞࠿ࡗࡓࠋ௒ᚋࡣཷ⫾ᛶపୗࡢ࣓࢝ࢽࢬ࣒࡜ཷ⫾ᛶྥୖࡲ࡛ࢆど㔝࡟ධࢀࡓ◊
✲ࢆ⾜ࡗ࡚࠸ࡃᚲせࡀ࠶ࡿ࡜⪃࠼ࡽࢀࡿࠋ
௨ୖࡼࡾ㸪➨ 2 ❶࠿ࡽ➨ 4 ❶ࡲ࡛࡟⾜ࡗࡓ◊✲࠿ࡽ㸪W1DF ࡢⓎ⫱ືែ㸪ᙧែ㸪༸⬊
ቨ⾑ὶ㸪᤼༸๓ᚋࡢ㢛⢏ᒙ⣽⬊ࡢᛶ㉁࠾ࡼࡧ᤼༸ᚋ࡟ᙧᡂࡉࢀࡿ㯤యࡢᛶ㉁ࢆ W2DF ࡜
ẚ㍑ࡋࡓ⤖ᯝ㸪άຊࡢ㧗࠸༸⬊࡛࠶ࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡾ㸪W1DF ࡀⓎ⫱ࡍࡿᮇ㛫ࡢప
࠸⾑୰ P4 ⃰ᗘࡀࡑࡢཎᅉࢆࡶࡓࡽࡋࡓ࡜᥎ᐹࡉࢀࡿࠋࡉࡽ࡟㸪W1DF ࡟ࡘ࠸࡚㸪㯤య࡜
ྠ୍༸ᕢ࡛ඹᏑࡍࡿሙྜ࡜༢⊂࡛ᏑᅾࡋඹᏑࡋ࡞࠸ሙྜ࡛ࡣ㸪୺ᖍ༸⬊ࡢᛶ㉁ࡀ␗࡞ࡿ
ࡇ࡜ࡀ♧ࡉࢀ㸪༸ᕢ࡬ࡢ⾑ὶࡢ㐪࠸ࡀࡑࡢᕪ␗ࢆࡶࡓࡽࡍ࡜᥎ ࡉࢀࡓࠋࡲࡓ㸪㯤య࡜
༸⬊ࡀඹᏑࡍࡿࡇ࡜ࡀேᕤᤵ⢭ᚋࡢཷ⫾⋡ࢆపୗࡉࡏࡓࡇ࡜࠿ࡽ㸪࢘ࢩࡢ⦾Ṫ⏕⌮࡟࠾
ࡅࡿ W1DF ࡢ᪂ࡓ࡞ᙺ๭࡟㛵ࡍࡿ▱ぢࡀᚓࡽࢀࡓࠋ
99
ㅰ㎡
ᮏ✏ࢆ⤊࠼ࡿ࡟⮫ࡳ㸪⤊ጞᚚ᠓⠜࡞ࡿᚚᣦᑟࢆ㈷ࡾࡲࡋࡓᖏᗈ␆⏘኱Ꮫ␆⏘Ꮫ⛉
⮫ᗋ⋇་Ꮫ◊✲㒊㛛 ᯇ஭ᇶ⣧෸ᩍᤵ㸪⩚⏣┿ᝅຓᩍ࡟ᚰ࠿ࡽᣏㅰࡋ㸪ᮏㄽᩥసᡂ
࡟࠶ࡓࡾᚚᰯ㜀㡬ࡁࡲࡋࡓᖏᗈ␆⏘኱Ꮫ ᐑཎ࿴㑻ᩍᤵ㸪ᒾᡭ኱Ꮫ ᒃᅾᐙ⩏᫛ᩍ
ᤵ㸪ᮾி㎰ᕤ኱Ꮫ ⏣୰▱ᕫ෸ᩍᤵ㸪ᒱ㜧኱Ꮫ ᮧ℩ဴ☻ᩍᤵ࡟῝ㅰ࠸ࡓࡋࡲࡍࠋ
ࡲࡓ㸪◊✲㐙⾜࡟࠶ࡓࡾ㸪ᚚ༠ຊ㸪ᚚຓゝ㡬ࡁࡲࡋࡓ㸪ᖏᗈ␆⏘኱Ꮫ ᐑᮏ᫂ኵᩍ
ᤵ㸪ΎỈ㝯෸ᩍᤵ㸪ⱴ㔝ග⠊ㅮᖌ࡟῝ㅰ࠸ࡓࡋࡲࡍࠋ
ࡑࡋ࡚㸪ᐇ㦂࡟༠ຊࡋ࡚ࡃࡔࡉࡗࡓ⋇་⮫ᗋ⦾ṪᏛ◊✲ᐊࡢ኱Ꮫ㝔⏕㸪Ꮫ㒊Ꮫ⏕
ࡢⓙᵝ࡟ឤㅰ࠸ࡓࡋࡲࡍࠋ
᭱ᚋ࡟㸪Ꮫ⏕⏕άࢆ㛗ࡁ࡟ࢃࡓࡾᨭ࠼࡚࠸ࡓࡔ࠸ࡓ୧ぶ࡟᭱኱ࡢឤㅰࡢពࢆ⏦ࡋ
㏙࡭ࡲࡍࠋ
100
ཧ⪃ᩥ⊩
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