Journal of Radiation Research and Applied Science ss Possible

Journal of Radiation Research
and Applied Sciences
J. Rad. Res. Appl. Sci., Vol. 3, No.2(A), pp. 357 - 372 (2010)
Possible Outcome of Fenugreek Seeds Powder
Administration on the Fertility of Female and Male
Albino Rat
M. F. Ibrahim and G. A. El-Tawill
Radiation Biology Department, National Centre for Radiation Research and
Technology (NCRRT), Atomic Energy Authority, Cairo, Egypt..
E–mail: [email protected]
Received: 28/9/2009.
Accepted: 7/3/2010.
ABSTRACT
Fenugreek (Trigonella foenum-graecum) is an annual plant from the family of
Papilionaceae-Leguminosae that has been credited with many medicinal
properties. The current study aims to evaluate the possible fertility activity of
fenugreek seeds powder on female and male albino rats.
To achieve the theme, fenugreek seeds powder (200 mg/rat) were daily
administered orally to both female and male Wistar rats for 15 and 30
consecutive days, after which the rats were sacrificed for both biochemical and
histopathological observations. Fenugreek treatment significantly decreased the
serum cholesterol levels in both female and male rats with a marked increase in
the ovary and testis cholesterol levels following 30 days of consecutive
administration.
The circulating serum female hormones showed an initial elevation at the end of
15 days of fenugreek intake followed by a significant drop in the group of rats
that continued to receive the daily fenugreek dose for 30 days. These
observations were supported by the notable decline in the ovarian weights
further validated by their ovarian histological sections revealing remarkable
dissolution of some follicles and prominent abundance of inflammatory cells.
In the 30 days interval treated males, the serum testosterone hormone
concentrations significantly declined and the testis weights were reduced with
evident damage to the seminiferous tubules and interstitial tissues as shown by
the histopathological picture of testis tissue sections.
Accordingly, it can be deduced that fenugreek seeds powder exert a significant
antifertility adverse effect on the female and male rats when supplemented at a
considerable dose for an extended time interval.
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INTRODUCTION
Fenugreek is an annual herb widely grown in India, Egypt and Middle
Eastern countries (1,2,3). Its seeds are commonly used for flavoring and as a spice
in curries due to their strong flavor and aroma. Fenugreek is known to lower
blood glucose level and partially restore the activities of key enzymes of
carbohydrate and lipid metabolism close to normal values in various animal
model systems (4). It can increase the erythrocyte insulin receptors and
peripheral glucose utilization, thus showing improved pancreatic function (5).
The antidiabetic and hypocholesterolemic activity of fenugreek is primarily
associated with the defatted fraction of its seeds (6-8)and can be largely attributed
to their saponin and high fiber content (1,2,9) .
As previously identified, fenugreek seeds contain about 12% by weight
steroidal saponins (including diosgenin and yamogenin) which are the building
blocks for various steroids, including cholesterol and male and female sex
hormones (10). The steroidal extract of fenugreek has been shown to exert an
antifertility and antiestrogenic activity in female rats (11). Also, feeding
fenugreek seeds to male albino rats (100 mg/day/rat) for 60 days increased their
testicular and serum cholesterol causing a drop in the circulating androgen and
hence altered the testicular histoarchitecture (12).
It has also been documented that low dose (0.05 ml/mouse) of
fenugreek oil intake showed no impaired effect on follicular development and
ovulation rate in the ovaries of the treated mice, whereas larger doses of
fenugreek oil (0.1 or 0.15 ml/ mouse) revealed marked congestion of interstitial
ovarian blood vessels and presence of numerous mature ovarian follicles and
multiple corpora lutea in ovaries of mice (13).
Furthermore, fenugreek seeds (30% in a diet) have been incriminated for
their negative impact on the testicular tissue as evidenced by the damage of
interstitial tissue, the decrease in the number of seminiferous tubules and mild
spermatogenic hypoplasia (14).
Consequently, the current study intends to appraise the female and male
reproductive response in different rat groups post fenugreek oral intake
throughout different time intervals holding several biochemical and histological
parameters.
MATERIALS AND METHODS
Experimental animals
A total number of 24 female and 24 male adult albino rats, Sprague
Dawley, weighing 120-150 g were caged separately (males apart from females).
Standard rodent pellets purchased from the Oil and Soap Company, Egypt and
tap water were provided ad libitum.
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Fenugreek (Trigonella foenum graecum)
Fenugreek, GNC herbal plus, FINGER PRINTED, was purchased from
General Nutrition Corp. Pittsburgh, PA 15222 (USA). Fenugreek seeds were
available in the form of capsules, each containing 500 mg Fenugreek powder.
The powder content of each capsule was dissolved in 10 ml of distilled water
and every rat was daily orally administered 4ml Fenugreek solution (200 mg /
rat) via an oral gavage for 15 or 30 consecutive days.
Experimental Design
A number of 12 female and 12 male rats were kept as control whereas
12 female and 12 male rats were fenugreek treated. Oral daily intake of either
distilled water to the control animals or fenugreek solution to the treated ones
were administered via an oral gavage.
Vaginal smears were checked daily during the experimentation. Control
and treated female rats were chosen to be either in the metoestrus or dioestrus
stage at the beginning of the experiment.
Experiments were performed according to the international guidelines
of animal handling and care (15).
Animals were divided into 4 female groups and 4 male ones as follows:
Group 1: A number of 12 female virgin normal rats receiving an oral daily dose
of 4 ml distilled water for 30 consecutive days served as normal control.
Group 2: A number of 12 female virgin rats receiving an oral daily dose of 4 ml
Fenugreek solution (200 mg / rat) for 30 consecutive days.
Group 3: A number of 12 male normal rats receiving an oral daily dose of 4 ml
distilled water for 30 consecutive days served as normal control.
Group 4: A number of 12 male rats receiving an oral daily dose of 4 ml
Fenugreek solution (200 mg / rat) for 30 consecutive days.
A number of 6 animals of each group were sacrificed on the 15th day of
treatment while the other 6 rats were sacrificed at the end of the
experimentation period (30 days).
On the assigned day, after being anaesthetized by light ether, blood was
collected by heart puncture after which the serum was separated by
centrifugation and then stored frozen at -20°C in small vials.
Concomitantly, the rats of each experimental group are cut open, the
ovaries and testes were removed, weighed and immediately fixed in buffered
formol. Sections were processed routinely for paraffin embedding and sectioned
at 6µ then stained with haematoxylin and eosin (HE) and mounted with Canada
Balsam. They were then examined by Olympus light microscope to detect the
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histological or histopathological changes in the ovaries and testes induced by
fenugreek treatment.
For biochemical analysis, serum and tissue content of cholesterol were
assayed according to Thomas(16). Female and male hormones were determined
by radioimmunoassay. Serum Follicle-stimulating hormone (FSH),
Progesterone, Estradiol, Luteinizing hormone (LH) and testosterone were
assayed according to Santner (17), Autrere & Benson (18), Bergquist et al. (19),
Burtis & Ashwood (20) and Albertini & Ekins (21), respectively.
Statistical evaluation of the data was carried out according to Snedecor
& Cochran (22). Treatment means were compared using Student’s t-test.
RESUITS AND DISCUSSION
The effect of oral administration of fenugreek seeds powder on some
physiological subjects in female and male rat groups is represented through data
displayed in Tables 1, 2 & 3.
Table 1 shows a significant decrease in the serum cholesterol
concentration in both females and males (- 10.73% & - 10.83% respectively)
following 15 days of subsequent treatment with a further significant decrease in
both sexes (- 19.6% in♀ & - 18.4% in♂) post 30 days of treatment as compared
to the relevant control groups.
However, in ovary and testis tissues, cholesterol levels show non-significant
change after 15 days (+18.82% in♀ & + 11.21% in♂) but after 30 days they
show significant increase in both ovary and testis (+ 37.36% & + 36.63%
respectively).
Table (1): Effect of fenugreek seeds powder administration on serum and tissue
cholesterol level in different rat groups.
Serum cholesterol mg/dl
Cholesterol in testis and
ovary tissues mg/g
♀
♂
♀
♂
70.8 ±1.66
72.0 ± 1.05
8.5 ± 0.8
10.7 ± 0.29
Control 15 days
63.2 ± 2.00*
64.2± 1.97*
10.1 ± 0.63
11.9 ± 0.88
Fenugreek
(- 10.73%)
(- 10.83%)
(+18.82%)
(+ 11.21%)
treated 15 days
72.3 ± 2.23
72.9± 1.88
9.1 ± 0.43
10.1 ± 0.51
Control 30 days
58.1± 2.16*
59.5± 1.31*
12.5 ± 0.75*
13.8 ± 0.73*
Fenugreek
(- 19.6%)
(- 18.4%)
(+ 37.36%)
(+ 36.63%)
treated 30 days
Each value represents the mean of 6 records.
Values between brackets show percentage of change.
*: Significantly different from control at P≤ 0.05.
Moreover, Table 2 shows that 15 days of fenugreek treatment caused a
significant increase in the level of female hormones (FSH, Progesterone and Es)
(+69.3%, + 53.79% & +11.38% respectively), whereas 30 days induced a
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significant decrease in FSH & progesterone hormones (-23.65% & -26%
respectively) and a nonsignificant change in the estrogen level (-5.10%) as
compared to the female sex hormones of the control groups.
Table (2): Effect of fenugreek seeds powder administration on serum folliclestimulating hormone (FSH), progesterone and estradiol (E2) in female
rats.
FSH
Progesterone
Estradiol (E2)
pg/dl
ng/ml
ng/ml
2.25±0.21
2.9±0.32
23.45±0.31
Control 15 days
3.81±0.34*
4.46±0.36*
26.12±0.29*
Fenugreek
(+69.3%)
(+ 53.79%)
(+11.38%)
treated 15 days
2.41±0.19
3.0±0.22
23.9±0.33
Control 30 days
1.84±0.09*
2.22±0.16*
22.68±0.39
Fenugreek
(-23.65%)
(-26%)
(-5.10%)
treated 30 days
Each value represents the mean of 6 records.
Values between brackets show percentage of change.
*: Significantly different from control at P≤ 0.05.
Also, 30 days of successive daily fenugreek seeds powder treatment
caused a significant decrease in LH and testosterone male sex hormones (15.1% & -13.23% respectively) as compared to the control values as displayed
in Table 3.
Table (3): Effect of fenugreek seeds powder administration on serum luteinizing
hormone (LH) and testosterone level in male rat groups.
LH
Testosterone ng/ml
mIu/ml
70.2±1.2
86.2±1.13
Control 15 days
73.1±1.8
90.2±2.5
Fenugreek treated 15
(+4.13%)
(+4.64%)
days
71.0±1.6
86.9±1.3
Control 30 days
60.3±1.5*
75.4±1.0*
Fenugreek treated 30
(-15.1%)
(-13.23%)
days
Each value represents the mean of 6 records.
Values between brackets show percentage of change.
*: Significantly different from control at P≤ 0.05.
Moreover, the data displayed in Table 4 indicate that the weights of
female and male reproductive organs, namely the ovary and testis, declined but
with a higher percentage following 30 days of fenugreek intake (-50% & -42%
respectively) as compared to the control rats.
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Table 4: Ovarian and testicular weights following fenugreek seeds powder
administration in female and male rat groups.
Ovarian weight (mg)
Testicular weight (g)
0.03±0.00
1.66±0.05
Control 15 days
Fenugreek treated 15
days
0.024±0.00*
-20%
1.36±0.02*
-18%
Control 30 days
Fenugreek treated 30
days
0.04±0.00
0.02±0.00*
-50%
1.62±0.03
0.94±0.16*
-42%
Each value represents the mean of 6 records.
Values between brackets show percentage of change.
*: Significantly different from control at P≤ 0.05.
Histopathological investigation of ovarian tissues from the fenugreek
treated group for 15 days showed high follicular development in the ovarian
section as represented in Figure 2 with respect to the control one displayed in
Figure 1.
Figure 1: Photomicrograph of a section in the ovary of a control rat receiving
distilled water for 15 days showing normal developing ovarian follicle
with mature corpus luteum (m), normal granulose cells (g) and theca
cells (th) (x200).
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Figure 2: Photomicrograph of a section in the ovary of a rat orally treated with
fenugreek for 15 consecutive days showing different stages of developed
ovarian follicles (f) (x200).
However, the 30 days fenugreek treated group showed remarkable
dissolution of the ovarian follicles surrounded by inflammatory cells as well as
high content of fibroblasts (Figure 4).
Figure 3: Photomicrograph of a section in the ovary of a normal rat receiving 4ml
distilled water for 30 days showing: 1.well-defined germinal epithelium,
2. normal tunica albuginea, 3. normal primordial follicles, 4. normal
primary follicles, 5. well-defined corpus luteum with normal granulose
cells and thecal cells (x200).
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Figure 4: Photomicrograph of a section in the ovary of a rat orally treated with
fenugreek for 30 days showing 1. dissolution of the ovarian follicles. 2.
high content of fibroblasts filled the section. 3. inflammatory cells
around the dissolved follicles (x200).
Moreover, testis sections of male rats administered fenugreek for 15
days represented in Figure 6 showed degeneration of some spermatogenic cells
together with arrest of maturation at spermatid level when compared to their
control section displayed in Figure 5. However, the consequences of fenugreek
treatment for 30 days (Figure 8) were more deleterious where the seminiferous
tubules showed disrupted basement membranes with necrotic changes in some
germinal cells and abnormal aggregation of some sperm cells. Also,
degeneration of interstitial stroma and congestion of blood capillaries were
prominent.
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Figure 5: Photomicrograph of a transverse section of a testis of a control rat
ingesting 4ml distilled water for 15 consecutive days showing:
-Normal seminiferous tubules embedded in a loose connective tissue stroma
containing interstitial Leydig cells (L)
- Typical arrangement of the germ cells including:
- Spermatogonia (S)
- Primary spermatocytes (Ps)
- Spermatid (Sp)
- Spermatozoa (Spz) (x 200).
Figure 6: Photomicrograph of a section of a rat testis orally treated with fenugreek
for 15 days showing degeneration of spermatogenic cells and arrest of
maturation at spermatid level (A) (x 200).
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Figure 7: Photomicrograph of a transverse section of a testis of a control rat
ingesting 4ml of distilled water for 30 consecutive days illustrating the
usual pattern of the seminiferous tubules shown in Figure 1 (x 200).
Figure 8: Photomicrograph of a section of a testis of a rat orally treated with
fenugreek for 30 days displaying:
- Disruption of the basement membrane of the seminiferous tubule (D).
- Necrotic changes in the germinal cells.
- Exfoliation and abnormal aggregation of sperm cells.
- Congested and dilated capillaries (C).
- Disruption or degeneration of interstitial stroma (x 200).
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DISCUSSION
Besides the common known functions of fenugreek seeds (Trigonella
foenum-graecum) to lower total cholesterol, promote fertility and promote milk
production, fenugreek seeds have also been shown to exert an antifertility
activity (11, 12, 23-26) due to their rich content of steroidal saponins (27). These
steroidal saponins, constituting about 12% by weight of fenugreek seeds, are the
building blocks for various steroids, including cholesterol and male and female
sex hormones (10).
The data presented herein revealed that daily oral administration of
fenugreek seeds powder (200 mg/rat) to female and male rats brought about a
significant decrease in the serum cholesterol level after 15 days followed by a
further decrease after 30 days. This observed hypocholesterolemic effect which
is proportional to the longer period of fenugreek intake may be attributed to the
rich saponin and high fiber content present in fenugreek seeds (28) or to an
increase in the conversion of cholesterol to bile acids or else to an increased
fecal excretion of bile acids and neutral sterols (29).
Moreover, the ovary and testis cholesterol significant increase in the 30
days fenugreek treated rat groups might indicate non-utilizing of cholesterol by
these mammalian cells in the synthesis of steroid hormones, due to the rich
abundance of steroidal saponins (containing these steroid hormones) in
fenugreek seeds (11).
In the current work, 15 days of 200 mg/rat supplementation of
fenugreek seeds powder resulted in significant increase in FSH, progesterone
and estrogen hormones in female rats. These findings were confirmed by the
high follicular development in the ovarian sections as displayed by the
histological picture following 15 days of fenugreek administration.
The steroidal components present in fenugreek seeds are precursor to
form estrogens. Estrogens, in which they are one of steroidal hormones in the
ovary (30) induce a sudden increase in gonadotropin-releasing hormone (GnRH)
secretion from the hypothalamus which stimulates secretion of folliclestimulating hormone (FSH) from the pituitary. FSH induces follicles to grow
and increase in size (31).
Therefore, the present observed hormonal elevation and follicular
development might be a result of an effect of these seeds on the stimulation of
the pituitary-ovarian axes to secrete FSH which improves maturation and
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ovulation rates of oocytes resulting in increased corpus luteum number and
progesterone levels in the circulation (14).
However, supplementation of these seeds for a longer period namely 30
days of daily intake resulted in significant depression in female hormone levels,
accompanied by apparent regression in their ovarian weight, further validated
by their ovarian histological sections revealing remarkable dissolution of some
follicles and prominent abundance of inflammatory cells.
The observed decline in the circulating estrogen level may be due to the
negative feedback mechanism of hormone system (32) since the excess
estrogenic activity of fenugreek seeds for 30 days might have disturbed the
female reproductive physiology. Since the structural and functional integrity of
the reproductive tissues depend on the circulating level of estrogen, therefore
any small change in estrogen level may result in reduction in the weights of the
reproductive organs (33). Accordingly, the low estrogen level recorded in the
present study might not have been enough to maintain the ovarian weights (11).
It can thus be concluded that the mechanism of action of fenugreek on
the ovarian activity may be attributed to the endocrine influence and/or the
chemicals components of fenugreek (13).
In case of male rats, administration of the high dose of fenugreek seeds
powder (200 mg/rat) for 30 days caused significant decrease in circulating LH
and testosterone hormones in addition to a significant reduction in testis weight.
This was evidenced by the histopathological picture displaying degeneration of
some spermatogenic cells, necrotic changes in the germinal cells and prominent
disruption of the interstitial stroma. The negative impact of fenugreek seeds on
the male structural and functional integrity of testicular tissue may support the
hypothesis that a component of these seeds may have a direct toxic effect on the
seminiferous tubules and the interstitial (Leydig) cells of the testis responsible
for the synthesis of androgens (12, 14).
Therefore, it can be concluded that supplementation of fenugreek seeds
powder at a considerable high dose of 200mg/rat/day over a short period of 15
days only revealed a positive fertility stimulatory activity on the female rats or a
negligible reproductive effect on male ones whereas a significant antifertility
adverse effect on the female and male rats has been recorded attributable to the
long period of 30 days fenugreek daily intake at the same dose level.
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Endocrinology, 85: 474-475.
‫ﻣﺠﻠﺔ اﻟﺒﺤﻮث اﻹﺷﻌﺎﻋﯿﺔ‬
‫واﻟﻌﻠﻮم اﻟﺘﻄﺒﯿﻘﯿﺔ‬
‫ﻣﺠﻠﺪ ‪ 3‬ﻋﺪد ‪)2‬أ( ص ص ‪(2010) 372 – 357‬‬
‫اﻟﺘﺄﺛﯿﺮ اﻟﺴﻠﺒﻲ اﻟﻤﺤﺘﻤﻞ ﻟﺘﻌﺎﻃﻲ ﻣﺴﺤﻮق ﺑﺬور ﻧﺒﺎت اﻟﺤﻠﺒﺔ ﻋﻠﻰ ﺧﺼﻮﺑﺔ إﻧﺎث‬
‫وذﻛﻮر اﻟﺠﺮذان‪.‬‬
‫ﻣﮭﺎ ﻓﻮزي إﺑﺮاھﯿﻢ و ﻏﺎدة أﺣﻤﺪ اﻟﻄﻮﯾﻞ‪.‬‬
‫ﻗﺴﻢ ﺑﺤﻮث ﺑﯿﻮﻟﻮﺟﯿﺎ اﻹﺷﻌﺎع‪ ،‬اﻟﻤﺮﻛﺰ اﻟﻘﻮﻣﻲ ﻟﺒﺤﻮث وﺗﻜﻨﻮﻟﻮﺟﯿﺎ اﻹﺷﻌﺎع‪ ،‬اﻟﻘﺎھﺮة‪ ،‬ﻣﺼﺮ‪.‬‬
‫ﻧﻈﺮاً ﻟﻤﺎ ﯾﺘﻤﺘﻊ ﺑﮫ ﻧﺒﺎت اﻟﺤﻠﺒﺔ )ﺗﺮاﯾﺠﻮﻧﯿﻼ ﻓﻮﻧﻢ ﺟﺮاﺳﯿﻮم( اﻟﺴﻨﻮي ﻣﻦ ﻣﻤﯿﺰات ﻃﺒﯿﺔ ﻋﺪﯾﺪة‬
‫ﻓﺈن ھﺬا اﻟﺒﺤﺚ ﯾﮭﺪف إﻟﻰ ﺗﻘﯿﯿﻢ ﻓﻌﺎﻟﯿﺔ ھﺬا اﻟﻨﺒﺎت ﻋﻠﻰ ﺧﺼﻮﺑﺔ إﻧﺎث وذﻛﻮر اﻟﺠﺮذان‪ .‬وﻟﺘﺤﻘﯿﻖ اﻟﮭﺪف ﻓﻘﺪ‬
‫ﺗﻢ إﻋﻄﺎء ﻣﺴﺤﻮق ﺑﺬور ﻧﺒﺎت اﻟﺤﻠﺒﺔ ﺑﺠﺮﻋﺔ ﻋﺎﻟﯿﺔ )‪ 200‬ﻣﻠﺠﻢ ﻟﻜﻞ ﻓﺄر( ﯾﻮﻣﯿﺎً ﻋﻦ ﻃﺮﯾﻖ اﻟﻔﻢ ﻟﻤﺪة ‪15‬‬
‫و‪ 30‬ﯾﻮﻣﺎًَ ﻣﺘﺘﺎﻟﯿﺔ ﺗﻢ ﺑﻌﺪھﺎ ذﺑﺢ اﻟﺠﺮذان ﻟﻔﺤﺺ اﻟﻨﺘﺎﺋﺞ اﻟﺒﯿﻮﻛﯿﻤﯿﺎﺋﯿﺔ واﻟﮭﯿﺴﺘﻮﺑﺎﺛﻮﻟﻮﺟﯿﺔ‪.‬‬
‫وﻗﺪ أوﺿﺤﺖ اﻟﻨﺘﺎﺋﺞ اﻧﺨﻔﺎض ﻣﻠﺤﻮظ ﻓﻲ ﻣﺴﺘﻮى اﻟﻜﻮﻟﺴﺘﺮول ﻓﻲ دم ﻛﻞ ﻣﻦ إﻧﺎث وذﻛﻮر‬
‫اﻟﺠﺮذان ﻣﻊ زﯾﺎدة ﻣﻠﺤﻮﻇﺔ ﻓﻲ ﻧﺴﺒﺔ اﻟﻜﻮﻟﺴﺘﺮول ﻓﻲ أﻧﺴﺠﺔ ﻣﺒﺎﯾﺾ وﺧﺼﻲ اﻟﺠﺮذان ﺑﻌﺪ ﺗﻨﺎوﻟﮭﺎ ﻣﺴﺤﻮق‬
‫ﺑﺬور ﻧﺒﺎت اﻟﺤﻠﺒﺔ ﻟﻤﺪة ‪ 30‬ﯾﻮم ﻣﺘﺘﺎﻟﯿﺔ‪ .‬ﻛﻤﺎ أﻇﮭﺮت ﻧﺘﺎﺋﺞ ﻗﯿﺎس ﻣﺴﺘﻮى ھﺮﻣﻮﻧﺎت اﻷﻧﻮﺛﺔ ﻓﻲ اﻟﺪم ارﺗﻔﺎع‬
‫ﻣﺒﺪﺋﻲ ﺑﻌﺪ ‪ 15‬ﯾﻮم ﻣﻦ اﻟﺘﻌﺎﻃﻲ أﺗﺒﻌﮫ اﻧﺨﻔﺎض ﻣﻠﺤﻮظ ﺑﻌﺪ ‪ 30‬ﯾﻮم‪ .‬وﻗﺪ ﺗﺄﻛﺪت ھﺬه اﻟﻨﺘﺎﺋﺞ ﺑﺎﻟﻨﻘﺺ‬
‫اﻟﻤﻠﺤﻮظ ﻓﻲ وزن اﻟﻤﺒﺎﯾﺾ وﺑﺎﻟﻨﺘﺎﺋﺞ اﻟﮭﯿﺴﺘﻮﻟﻮﺟﯿﺔ اﻟﺘﻲ أوﺿﺤﺖ اﻟﺘﺤﻠﻞ اﻟﻮاﺿﺢ ﻟﻠﺤﻮﯾﺼﻼت واﻟﺰﯾﺎدة‬
‫اﻟﻤﻠﺤﻮﻇﺔ ﻓﻲ ﻋﺪد اﻟﺨﻼﯾﺎ اﻟﻤﻠﺘﮭﺒﺔ‪.‬‬