Chapter 28, Part 2!
Female Reproductive System!
Chapter 28, Part 2!
The Female Reproductive System!
SECTION 18-3!
Oogenesis occurs in the ovaries, and
hormones from the pituitary gland and
gonads control female reproductive functions!
2!
The Female Reproductive System
Figure 28-13!
3!
1!
Chapter 28, Part 2!
Female Reproductive System!
Ovaries, Uterine Tube and Uterus
Figure 28-14!
4!
Ovaries!
Female gonads - homologous to testes!
Ligaments hold ovaries loosely in place!
Broad ligament!
•  Double fold of peritoneum!
•  Encloses internal reproductive structures!
Round ligament!
•  Uterus → inguinal canal→ CT of external genitalia!
Ovarian ligaments!
•  Anchor ovaries to uterus!
Suspensory ligaments!
•  Anchor ovaries to pelvic wall!
5!
Ovarian Histology!
Germinal epithelium!
•  Serosa of ovary!
Tunica albuginea!
•  White, dense irregular CT!
•  Deep to germinal epithelium!
Ovarian stroma!
1.  Cortex!
•  Deep to tunica albuginea!
•  Dense CT + follicles!
2. Medulla!
•  Loose CT!
•  N.A.V.a.L.!
6!
2!
Chapter 28, Part 2!
Female Reproductive System!
Oogenesis
Figure 28-15!
Mitosis !
2n!
1D!
before birth!
2n!
2D!
Meiosis I begun!
before birth!
Meiosis I completed!
n!
1D !
after puberty!
Error in
9th edition
Meiosis II!
Completed if
fertilization
occurs!
n!
1/2D!
7!
Oogenesis!
Production of eggs (ova)!
Primordial germ cells migrate to ovaries from
endoderm!
•  Differentiate within ovary into oogonia!
•  Mitosis before birth produces millions of germ
cells!
•  Most degenerate (atresia)!
•  Some differentiate into primary oocytes!
8!
Primary Oocytes!
Enter meiosis I, stop in prophase!
Do not complete Meiosis I until after puberty!
•  At birth, up to 2 million primordial follicles
(with primary oocytes) remain (number is
highly variable)!
•  By puberty, atresia leaves about 400,000!
•  About 400-500 will mature and ovulate!
•  FSH stimulates development of oocyte!
9!
3!
Chapter 28, Part 2!
Female Reproductive System!
Review Article on Follicle Development!
Erickson, GF, Follicle Growth and Development!
Glob. libr. women’s med., (ISSN: 1756-2228) 2008;
DOI 10.3843/GLOWM.10289!
Link:
http://www.glowm.com/section_view/heading/
Follicle Growth and Development/item/288!
!
134 references!
You are not responsible for the information on
slides that are grayed out. This is very
interesting newer information, but is FYI only.!
10!
Ovarian Follicles – 1!
Reproductive physiologists recognize:!
•  Primordial follicles!
•  Primary preantral follicles!
•  Secondary preantral follicles!
•  Tertiary (early antral follicles)!
•  Graafian (antral) follicles:!
1.  Healthy Graafian!
•  One of several in a cohort is usually
SELECTED for ovulation!
2.  Atretic Graafian!
11!
Ovarian Follicles – 2
Figure 2 from Erickson, 2008!
v  Note that many follicles of each type (except
dominant follicle) would be present at any one
time.!
12!
4!
Chapter 28, Part 2!
Female Reproductive System!
Primordial Follicles!
Consist of a primary oocyte and a single layer of
squamous cells!
•  Oocyte arrested in prophase of Meiosis I!
•  Primordial follicle development
(RECRUITMENT) is independent of FSH, LH!
•  Evidence for this:!
o  Basement membrane of granulosa cells and
lack of own blood supply limits endocrine
effects!
o  Development to primary follicle occurs in fetus
soon after formation!
o  Development and antrum formation occurs
even after removal of pituitary!
Ovary Reserve!
13!
Erickson, 2008!
Pool of primordial follicles is the ovary reserve!
1 million !
at birth!
Recruitment leaves
about 24,000 at 37
years!
14!
Recruitment Mechanism!
Recruitment = process in which primordial follicles
start to develop into primaries!
•  Granulosa cells become mitotic!
Mechanism unknown!
•  Independent of pituitary hormones!
•  Probably paracrine/autocrine changes in
granulosa cells!
•  May be loss of inhibitory signal(s)!
o  Recruitment occurs rapidly after
primordials are removal from ovary!
15!
5!
Chapter 28, Part 2!
Female Reproductive System!
Recruitment Hypotheses!
1. Exposure to nutrients or regulators in the blood!
•  Occurs in primordials that are nearest medulla
where most vessels are found!
2. Internal oocyte clock!
•  Depends upon when oocyte began meiosis in
the embryo!
Some type of ligand-receptor pathway probably
involved!
•  Recruitment slowed in newborn rats by:
thymus removal, starvation, opioid injections!
16!
Primary Follicles (Preantral) – 1!
Squamous EPI → cuboidal!
•  Cells divide → several layers of cells!
•  No antrum!
•  Cells begin to express FSH receptors!
•  But normal plasma FSH not important
because primary follicles lack a blood
supply!
•  Development from primordial follicle to
healthy Graafian follicle takes about one
year.!
17!
Primary Oocyte in Primary Follicle!
Oocyte growing and differentiating!
1. ZP genes activated → Zona pellucida appears!
•  Glycoprotein layer between oocyte and
granulosa cells!
•  Microvilli of granulosa cells and oocyte merge!
Increases surface area for oocyte nutrition!
•  ZP contains ZP3 receptor = sperm receptor!
2. Gap junctions forming between oocyte and
granulosa cells!
•  Follicle becomes an electrical/functional
syncytium
18!
6!
Chapter 28, Part 2!
Female Reproductive System!
Secondary (Preantral) Follicle Characteristics!
•  Full-sized oocyte!
o  Meiosis can now resume, but NORMALLY
DOES NOT!
o  Inhibitor unknown !
•  Zona pellucida!
•  6-9 layers of granulosa cells (i.e. stratified)!
•  Basal lamina!
•  Theca interna!
•  Theca externa!
•  NO ANTRUM (different from lab)!
19!
Secondary (Preantral) Follicle Regulation of Mitosis!
Regulation of granulosa cell mitosis!
•  GDF-9 (growth differentiation factor) required in
rats!
•  No GDF-9, development stops here!
•  I.e. oocyte is important for regulating follicle
development by producing factors like GDF-9!
!
20!
Secondary (Preantral) Follicle – Theca (1)!
Blood vessels develop around follicle !
•  (i.e. follicle now has blood supply)!
•  Nutrients, FSH/LH can reach follicle!
All theca cells around follicle now have FSH
receptors!
•  This MAY allow cells to respond to FSH!
Some thecal cells develop LH receptors:!
•  Become theca interna!
•  Involved in estrogen production together
21
with granulosa cells!
!
7!
Chapter 28, Part 2!
Female Reproductive System!
Secondary (Preantral) Follicle – Theca (2)!
Some theca cells become smooth muscle cells of
theca externa!
•  Autonomic innervation!
•  May contract during ovulation and atresia!
!
Meiosis can now resume, but NORMALLY DOES
NOT!
•  Inhibitor unknown (may involve cAMP from
granulosa cells)!
•  Meiosis normally resumes in preovulatory
(antral) stage in response to LH!
22!
Tertiary (Early Antral) Follicle!
Defined by appearance of antrum!
•  Antrum formation called cavitation!
FSH not required for antrum formation !
•  Hypophysectomy → antrum still forms!
Probably para-/autocrine mechanism!
•  Activin!
•  KIT ligand (aka stem cell factor or c-Kit)!
o  Treat with activin → antrum forms!
o  Block KIT ligand → no antrum, no ovulation!
o  Gap junctions required!
23!
Graafian (antral) Follicle!
THERE COULD BE MANY OF THESE PRESENT!
Large antral cavity!
Almost nothing is known about importance of
antrum and antral fluid, but it is present in all
mammals!
BUT FSH WILL ACCUMULATE IN THE ONE THAT
IS SELECTED TO BECOME DOMINANT
FOLLICLE!
Theca layers are now functional!
•  LH regulates androstenedione secretion by
theca interna!
24!
8!
Chapter 28, Part 2!
Female Reproductive System!
Graafian Follicle Granulosa Cell Layers!
1. Zona (membrana) granulosa (next to theca)!
Pseudostratified columnar, anchored to
basal lamina!
2. Periantral layer (next to antrum)!
3. Corona radiata (immediately next to
oocyte)!
4. Cumulus oophorus (between other layers)!
ALL LAYERS EXPRESS FSH RECEPTORS!
!
25!
Types of Graafian Follicles – 1!
1. Healthy!
•  Takes 2 months to reach preovulatory state!
•  Express genes for differentiation, proliferation,
fluid formation!
•  Apoptosis inhibited somehow!
•  Small → medium → large size!
Size depends mostly on antral fluid volume!
•  Fluid volume depends on [FSH] in fluid!
•  Believed proportional to growth and
development!
26!
Types of Graafian Follicles – 2!
2. Atretic!
•  Apoptosis genes activated somehow!
•  Do not reach large size!
!
!
Follicles of different types occur together at any
one time in the ovary!
!
27!
9!
Chapter 28, Part 2!
Female Reproductive System!
Selection of the Dominant Follicle!
Secondary ↑ in FSH required for selection to occur
(see Fig. 28-24)!
Increase in plasma FSH allows one follicle to
accumulate high [FSH] in the antral fluid. !
•  This only occurs in one follicle, but mechanism
is unknown!
•  High FSH causes growth and development in
dominant follicle!
Fluid [FSH] → high aromatase → high fluid
[estrogen]!
•  High [estrogen] inhibits FSH release and prevents
other follicles from developing !
28!
Oogenesis – Polar Bodies!
LH surge → Meiosis I resumes!
Primary oocyte produces: !
1. One secondary oocyte!
•  Haploid, but chromosomes are
bivalents (total 1 “dose” of
DNA)!
•  Meiosis stops at metaphase II!
•  Completed only if fertilized!
2. Other forms first polar body
•  Receives little cytoplasm!
•  Discarded!
29!
30!
10!
Chapter 28, Part 2!
Female Reproductive System!
Oogenesis!
Life: The Science of Biology!
Pruves et al. 2001!
31!
Ovulation!
“LH surge”!
Graafian follicle releases
secondary oocyte!
•  Released into
pelvic cavity!
•  Corona radiata
adheres to oocyte!
•  Enters uterine tube!
32!
Formation of Corpus Luteum!
Under influence of LH!
Granulosa cells remaining in ovary
proliferate!
•  Produce progestins!
e.g. progesterone!
•  Prepare uterus for pregnancy!
33!
11!
Chapter 28, Part 2!
Female Reproductive System!
Fate of Corpus Luteum!
If no implantation:!
•  Degenerates after about 12 days!
•  Decreasing [progestins] → menses!
•  Corpus albicans (scar) forms!
If fertilization and implantation:!
•  Corpus luteum maintained (see chapter 29)!
•  Completion of Meiosis II follows fertilization!
•  Second polar body and ovum formed!
•  Nuclei of sperm and ovum unite!
•  Zygote formed!
Uterine Tubes - Anatomy
34!
Figure 28-17!
http://www.britannica.com/science/uterus!
35!
Uterine Tube Anatomy – 2!
Entire tube about 4” long!
Anatomy!
1. Infundibulum (“funnel”)!
•  Ovarian end of tube!
•  Opens into pelvic cavity!
•  Has fimbriae!
o  Finger-like projections!
o  One usually in contact with ovary!
o  Highly folded ciliated mucosa!
o  Sweep fluid into tube!
36!
12!
Chapter 28, Part 2!
Female Reproductive System!
Uterine Tube Anatomy – 3!
2. Ampulla!
•  Widest, longest portion (2/3 of length)!
•  Fertilization usually occurs here!
Occurs up to 24 h after ovulation!
Takes ovum 3–4 days to reach uterus!
3. Isthmus!
•  Connection with uterus!
•  About 1/3 of length (Figure 28-18 in text is
somewhat misleading.)!
37!
Uterine Tube Histology!
Mucosa!
•  Ciliated simple columnar EPI!
•  Help move oocyte to uterus!
•  Secretory cells!
Nutrition for oocyte?!
Muscularis!
•  Inner circular, outer longitudinal smooth muscle!
•  Peristalsis helps move oocyte!
•  Begins a few hours before ovulation!
Serosa!
•  Part of broad ligament - mesosalpinx!
The Uterus
38!
Figure 28-18!
39!
13!
Chapter 28, Part 2!
Female Reproductive System!
Uterus!
Functions:!
•  Menstruation!
•  Implantation!
•  Fetal development (gestation)!
•  Labor!
Anatomy:!
•  Fundus (“bottom”)!
•  Cervix (“neck”)!
•  Body !
40!
Cervix and Cervical Mucus!
Cervix has two openings!
•  Internal os (os = “mouth”)!
Opening into uterus!
•  External os!
Opening into vagina!
Cervical mucus!
Glycoprotein, protein, lipids, enzymes, water!
A.  Non-ovulatory periods!
•  Mucus thick, forms cervical plug!
•  Prevents pathogens from entering uterus!
41!
Cervical Mucus – 2!
B.  Ovulatory periods!
Protects sperm from vaginal environment!
•  Mucus thinner!
•  pH higher!
•  Contains nutrients for sperm!
•  Chemicals may assist in capacitation of
sperm!
42!
14!
Chapter 28, Part 2!
Female Reproductive System!
Uterine Histology – 1!
Three major layers:!
1. Perimetrium!
Perimetrium!
•  Serosa = visceral
peritoneum!
2. Myometrium!
•  Three smooth muscle
layers!
•  Thickest in fundus!
•  Thinnest in cervix!
•  Responds to oxytocin!
43!
Uterine Histology – 2!
3.  Endometrium = mucous membrane!
a.  Simple ciliated columnar EPI!
b.  Endometrial glands derived from EPI!
•  Secrete glycogen and lipids!
Growth promoted by estrogen!
Secretion promoted by progesterone!
•  Produce nutrients for early divisions of
fertilized ovum!
c.  Endometrial stroma (lamina propria)!
•  Loose CT, N.A.V.a.L.!
44!
Endometrial Layers!
1. Stratum functionalis
(functional layer)!
•  Shed during
menses!
2. Stratum basalis!
Perimetrium
•  Temporary lining!
•  Permanent layer!
•  Regenerates
s. functionalis!
45!
15!
Chapter 28, Part 2!
Female Reproductive System!
The Uterine Blood Supply
Figure 28-19!
Large blood supply
Spiral artery!
necessary for:!
•  Growth of stratum
functionalis after
menses!
Straight artery!
•  Providing nutrients
to implanted
blastocyst!
•  Development of
placenta!
Uterine artery!
Spiral arteries supply
the s. functionalis.!
The Uterine Cycle
46!
Figure 28-20!
47!
The Uterine Cycle – 1!
a.k.a. menstrual cycle, female sexual cycle!
Average = 28 days (highly variable)!
1.  Menses (menstruation)!
2.  Proliferative phase!
3.  Secretory phase!
1. Menses
Stratum functionalis degenerates!
↓ progesterone → spiral arteries constrict → !
↓ blood flow → ↓ O2 and nutrients!
Tissue dies, sloughs away!
48!
16!
Chapter 28, Part 2!
Female Reproductive System!
Uterine Cycle – 2!
2.  Proliferative phase follows menses!
S. Functionalis proliferating (being
replaced)!
• 
Increased estrogen from
developing follicles!
Begin preparing uterus for fertilized
ovum!
• 
Mucus glands grow,
synthesizing glycogen-rich
mucus!
• 
Blood vessels growing (spiral
arteries)!
49!
Uterine Cycle – 3!
3.  Secretory phase
•  Increased progestins (and
estrogens) from corpus luteum!
•  Glands enlarged, very secretory!
•  More vessel growth!
50!
Vagina – Anatomy!
Vagina = “sheath”!
Passageway for:!
•  Sperm (accepts penis during intercourse)!
•  Menstrual flow!
•  Childbirth!
Attaches to uterus via cervix!
•  Fornix (arch) extends superiorly, surrounds
cervix!
Hymen = “membrane”!
•  May partially close vaginal orifice!
51!
17!
Chapter 28, Part 2!
Female Reproductive System!
Vagina – Histology!
1. Mucosa!
•  Lined by non-keratinized stratified squamous
epithelium!
•  Has folds called rugae!
•  Secretes organic acids!
(Low pH retards bacterial growth)!
2. Muscularis!
• 
Inner circular, outer longitudinal smooth muscle!
3. Adventitia!
•  Anchors to surrounding structures!
52!
External Genitalia (Vulva) – 1!
Vulva = “to wrap around”!
1. Mons pubis!
•  Adipose, skin, pubic hair over pubic
symphysis!
2. Labia (“lips”)!
•  Labia majoris (labium majus) = outer!
•  Labia minora (labium minus) = inner!
3. (Glans) clitoris (with prepuce)!
•  Erectile!
•  Homologous to CCP/glans penis!
53!
External Genitalia (Vulva) – 2!
4. Vestibule = region between labia minora!
• 
Vaginal orifice!
• 
External urethral orifice!
• 
Paraurethral glands (mucus)!
• 
Greater vestibular glands!
Homologous to prostate!
Homologous to bulbourethral glands!
5. Bulb of vestibule!
• 
Erectile tissue!
• 
Homologous to CCU/bulb of penis!
54!
18!
Chapter 28, Part 2!
Female Reproductive System!
Female External Genitalia
Figure 28-22!
55!
Mammary Glands!
Modified sudoriferous glands!
Synthesize, secrete, eject milk!
•  Process called lactation!
Each consists of 15-20 lobes!
•  Lobes contain lobules!
•  Lobules contain alveolar glands!
56!
Mammary Glands
Figure 28-23!
57!
19!
Chapter 28, Part 2!
Female Reproductive System!
Hormones!
Please be very familiar with Figure 28-24 and the
study guide posted for this figure.
GnRH!
•  Released in pulses!
•  Pulse frequency varies, affects release of FSH,
LH!
FSH!
•  Stimulates follicular growth in antral follicles**!
LH!
•  Maturation of dominant follicle!
(FSH and LH receptors upregulated)!
•  Ovulation and formation of corpus luteum!
Steroid Hormone Synthesis
58!
Figure 28-25!
59!
Estrogens – 1!
Primarily β-estradiol (with estrone, and estriol)!
Functions:!
1. Development (at puberty) and maintenance of:!
a)  Female reproductive structures!
b)  Secondary sexual characteristic!
•  External genitalia enlarge!
•  Vaginal epithelium changes!
Simple cuboidal → stratified squamous!
•  Uterus enlarges!
60!
20!
Chapter 28, Part 2!
Female Reproductive System!
Estrogens – 2!
•  Regional fat distribution pattern!
•  Fallopian tubes!
Increased number of glands!
Increased number of ciliated cells!
•  Voice pitch changes!
•  Breasts!
Increased development of stroma!
Increased development of ducts!
Increased fat deposition!
61!
Estrogens – 3!
2.  Protein anabolism!
• 
Synergistic with hGH!
3. Skeletal effects!
• 
Increases o’blast activity!
• 
Closes epiphyseal plates!
• 
Broadens pelvis!
4.  Increases metabolic rate!
5.  Skin smooth!
• 
Increases thickness!
• 
Increases vascularity, apocrine gland activity!62!
Estrogens – 4!
6.  Lowers blood cholesterol!
7.  Electrolyte effects!
• 
Mimics aldosterone!
↑  Na+ reabsorption → water retention!
!
!
63!
21!
Chapter 28, Part 2!
Female Reproductive System!
Progesterone – 1!
Mainly from corpus luteum!
Acts with estrogen to:!
1. Prepare uterus for implantation!
• 
Increased secretion by uterine glands!
• 
Decreased uterine contractions!
(Don’t expel egg!)!
2. Prepare mammary glands for milk secretion!
• 
Increase size of cells, secretion!
• 
Other hormones also involved!
64!
Progesterone – 2!
3. Fallopian tubes!
• 
Increase secretion (nutrients for egg)!
4. Electrolyte effects!
• 
• 
Also binds aldosterone receptor, but LESS
EFFECTIVE than aldosterone!
Overall effect of progesterone binding is !
↓ Na+ reabsorption and ↓ water retention!
65!
Other Hormones!
Inhibin!
Sources:!
•  Granulosa cells of developing follicles!
•  Corpus luteum!
Inhibits FSH (and LH)!
Relaxin!
From corpus luteum!
•  Relaxes uterus to ease implantation!
From placenta!
•  Relaxes uterus, pubic symphysis!
•  May help dilate cervix!
66!
22!
Chapter 28, Part 2!
Female Reproductive System!
Hormone Regulation
Figure 28-24, left!
67!
Hormonal Regulation – 2
Figure 28-24, right!
Generally:!
!
Estrogen increases
GnRH pulse frequency!
!
Progesterone decreases
GnRH pulse frequency!
68!
Feedback oscillation of hypothalamic-pituitary-ovarian system
1. Post-ovulatory depression of LH, FSH and GnRH by ovarian hormones
1A.
Corpus luteum is producing:
high progesterone
moderate estrogens
inhibin
Negative feedback of progesterone and estrogens on:
Anterior pituitary →
decrease LH
decrease FSH
Hypothalamus →
decrease GnRH
1A**
Negative feedback of inhibin:
Anterior pituitary →
1B.
decrease FSH (and LH)
Corpus luteum is degenerating:
decreased progesterone
decreased estrogen
decreased inhibin
Removal of negative feedback on GnRH, FSH, LH
2. Follicular growth phase
2A.
GnRH → FSH (and LH) release → Follicles developing
2B.
Slight decrease in FSH and LH caused by:
Follicular development → increased estrogen secretion
Negative feedback from moderate estrogen and low progesterone
3. Pre-ovulatory surge in FSH and especially LH
Positive feedback on anterior pituitary from:
Causes: ↑ GnRH →
high estrogens
low progesterone
(mechanism unknown)
Increased FSH
LH surge
(required ovulation and corpus luteum formation)
69!
23!
Chapter 28, Part 2!
Female Reproductive System!
Menopause!
Reproductive years = menarche → menopause!
Pool of ovarian follicles exhausted between ages 40 - 50!
Few follicles to respond to FSH and LH!
Causes decline in estrogen levels!
•  Cessation of reproductive cycle!
•  Changes in secondary sex characteristics!
•  Some atrophy of reproductive organs!
•  Osteoporosis!
•  Increased heart disease!
Pattern of GnRH pulses may also change!
Coincident with hot flashes, sweating!
70!
24!