Download Female reproductive physiology

Lec.2
Review of Female reproductive physiology
The most obvious manifestation of the normal menstrual cycle is the
presence of regular menstrual periods. These occur as the endometrium is
shed following failure of implantation or fertilization of the oocyte.
An intact hypothalamo-pituitary-ovarian axis is required for normal
menstruation.
I-Ovary:
Within the ovary, the menstrual cycle can be divided into three phases:
1- follicular phase.
2- ovulation.
3- luteal phase.
1-The follicular phase:
The ovary contain thousands of primordial follicles. These initial stages
of follicular development are independent of hormonal stimulation. In the
absence of the correct hormonal stimulus, follicular development fails at
the preantral stage, with ensuing follicular atresia. Development beyond
the preantral stage is stimulated by LH and FSH (key regulator of oocyte
development).
At the start of the menstrual cycle, FSH levels start to rise as the pituitary
is released from the negative feed back effects of progesterone, oestrogen
and inhibin. Rising FSH rescue a cohort of follicles from atresia.
The basis of hormonal activity in preantral to preovulatory follicles is
described as the (two cells, two gonadotrophin) hypothesis. The two
cells are theca and granulosa cells. These two cells are responsive to two
gonadotrophin LH and FSH respectively.
Within the theca cells, LH stimulates the production of androgen from
cholestrol. Within the granulosa cells, FSH stimulates the conversion of
thecally derived androgens to estrogens (aromatization). Normally only
one of these follicles is destined to grow to a pre-ovulatory follicle and be
released at ovulation ( the dominant follicle). The dominant follicle is the
largest and most developed follicle in the ovary at the mid-follicular
phase. So the largest follicle therefore requires the lowest levels of FSH
and LH for continued development. At the time of follicular selection,
FSH are declining in response to the negative feed back effects of
oestrogen. Therefore the dominant follicle is the only follicle that is
capable of continued development in the phase of falling FSH levels.
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2- the ovulation:
Late in the follicular phase, FSH induces LH receptors on granulosa
cells. As the dominant follicle develops further, follicular estrogen
production increases. This lead to a +ve feed back effect on the pituitary
LH secretion. LH levels increase at first slowly (day 8-12) and then more
rapidly (day 12 on wards). During this time, LH induces luteinization of
granulosa cells in the dominant follicle, so that progesterone is produced
and this will further amplifies the +ve feed back effect of estrogen on
pituitary LH secretion, leading to a surge of the LH. Ovulation occurs 36
hours after the onset of the LH surge. At the time of ovulation, the LH
surge stimulates the resumption of meioses, a process which is completed
after the sperm enters the egg. The increase in FSH, LH and progesterone
stimulate the proteolytic enzymes within the follicle cause follicular wall
break down and release of the oocyte.
3-Luteal phase:
This phase characterized by the production of progesterone from the
corpus luteum within the ovary. The corpus luteum is derived both from
the granulosa cells and from some of theca cells. The duration of the
luteal phase is fairly constant, being around 14 days in the most women.
In absence of pregnancy and the production of HCG from the embryo, the
corpus luteum regress at the end of the luteal phase, a process known as
leuteolysis this lead to decrease in oestrogen, progesterone and inhibin
levels and the pituitary is released from the negative feed back effects of
these hormonens, and gonadotrophins, particularly FSH start to rise and a
further menstrual cycle is initiated.
II- Pituitary gland:
The pituitary gland hormones LH and FSH are key regulators of
folliculo- geneses. The output of these hormones is stimulated by pulses
of gonadotrophin releasing hormone (GnRH) produced by the
hypothalamus. The response of the pituitary is not constant, but is
modulated by ovarian hormones, particularly oestrogen and progesterone.
III- Hypothalamus:
The pulsatile secretion of GnRH, stimulates pituitary LH and FSH
secretion. There is an alteration in the amplitude and frequency of GnRH
through out the cycle.
IV- Endometrium:
The endometrium undergo cyclic changes during the menstrual cycle.
These changes can be divided into the following:
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1. Menstruation.
2. The proliferative (follicular) phase.
3. The secretary (luteal) phase.
1- Menstruation:
Is the shedding of the dead endometrium and ceases as the endomertrium
regenerates. In an ovulatory cycle, the endometrium becomes
decidualized ( oestrogen and then progesterone in an orderly manner )
during the 2nd half of the cycle to allow implantation of the embryo. If
implantation does not occur, apoptosis occurs. Menstruation is initiated
by the withdrawal of oestrogen and progesterone. This lead to intense
spiral artery vasoconstriction ( indirect effect) and then lead to ischemia
and tissue damage, shedding of functional endometrium ( stratum
compactum and stratum spongiosum ) and bleeding from fragments of
arterioles remaining in the basal endometrium.
Haemostasis is secured by spiral artery vasoconstriction and scaring is
reduced by enhanced fibrinolysis, which breaks down blood clots. Later,
repair of the endometrium and new vessel formation ( angiogenesis) lead
to complete cessation of bleeding within 5-7 days from the start of the
menstrual cycle.
2- The proliferative phase:
Under the effect of oestrogen the follicular phase characterized by
glandular and stromal growth. The epithelium lining of the endometrial
glands changes from a single layer of low columnar cell to pseudostratifid
epithelium with frequent mitosis.
The endometrium thickness increased from 0.5mm at menstruation to
3.5mm at the end of the proliferative phase.
3- The secretary phase:
Under the action of progesterone (from the corpus luteum) this phase is
characterized by glandular secretary activity with inhibition of
proliferation. Subnuclear intracytoplasmic granules appear in the cells
and their content are released into the endometrial cavity. The gland
become tortuous and the stroma becomes edematous and the spiral arties
continue to extend into the superfacial layer of endometrium and become
convoluted (these changes occur only after ovulation). The peak secretory
activity occurs at time of implantation (7 days after the gonadotrophin
surge)
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In the late secretory phase, progesterone induces irreversible
decidualization of the stroma. Immediately prior to menstruation the
endometrium shows three distinct zones:
1. Stratum basalis (25%) which is retained during menstruation and
shows few changes during the cycle.
2. Stratum spongiosum (in the mid 50%) edematous stroma and
exhausted glands
3. Stratum compactum ( upper layer 25%) with prominent
decidualized stromal cells.
The withdrawal of estrogen and progesterone leads to collapse of the
deciualized endometrium, repeated vasoconstriction and relaxation of the
spiral arterioles, and consequent shedding of the endometrium. The onset
of menstruation heralds the end of one menstrual cycle and the beginning
of the next.
Normal menstrual cycle (clinical features):
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Cycle duration 28 days (21-35).
Duration of blood flow 3-7 days (2-8).
Peak flow on the 1st or 2nd day.
Normal menstrual loss 35ml/month (max. 80ml).
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