Monday, June 25, 2007


Ovarian Cycle
At puberty, the female begins to undergo regular
monthly cycles. These sexual cycles are controlled
by the hypothalamus. Gonadotropin-releasing hormone
(GnRH) produced by the hypothalamus acts on
cells of the anterior pituitary gland, which in turn secrete
gonadotropins. These hormones, follicle-stimulating
hormone (FSH) and luteinizing hormone (LH), stimulate
and control cyclic changes in the ovary.
At the beginning of each ovarian cycle, 15 to 20 primary
(preantral) stage follicles are stimulated to grow under the
influence of FSH. (The hormone is not necessary to promote
development of primordial follicles to the primary follicle stage,
but without it, these primary follicles die and become atretic.) Thus,
FSH rescues 15 to 20 of these cells from a pool of continuously
forming primary follicles (Fig. 2.1). Under normal conditions, only
one of these follicles reaches full maturity, and only one oocyte is
discharged; the others degenerate and become atretic. In the next
cycle, another group of primary follicles is recruited, and again, only
one follicle reaches maturity. Consequently, most follicles degenerate
without ever reaching full maturity. When a follicle becomes atretic,
the oocyte and surrounding follicular cells degenerate and are replaced
by connective tissue, forming a corpus atreticum. FSH also stimulates
maturation of follicular (granulosa) cells surrounding the oocyte. In
turn, proliferation of these cells is mediated by growth differentiation
factor-9 (GDF-9), a member of the transforming growth factor-β (TGF-β) family.
In cooperation, granulosa and thecal cells produce estrogens that (a) cause the
uterine endometrium to enter the follicular or proliferative phase; (b) cause
thinning of the cervical mucus to allow passage of sperm; and (c) stimulate the
pituitary gland to secrete LH. At mid-cycle, there is an LH surge that (a) elevates
concentrations of maturation-promoting factor, causing oocytes to complete
meiosis I and initiate meiosis II; (b) stimulates production of progesterone
by follicular stromal cells (luteinization); and (c) causes follicular rupture and

In the days immediately preceding ovulation, under the influence of FSH and
LH, the secondary follicle grows rapidly to a diameter of 25 mm. Coincident
with final development of the secondary follicle, there is an abrupt increase in
LH that causes the primary oocyte to complete meiosis I and the follicle to enter
the preovulatory stage. Meiosis II is also initiated, but the oocyte is arrested in
metaphase approximately 3 hours before ovulation. In the meantime, the surface
of the ovary begins to bulge locally, and at the apex, an avascular spot, the
stigma, appears. The high concentration of LH increases collagenase activity,
resulting in digestion of collagen fibers surrounding the follicle. Prostaglandin
levels also increase in response to the LH surge and cause local muscular contractions
in the ovarian wall. Those contractions extrude the oocyte, which
together with its surrounding granulosa cells from the region of the cumulus
oophorus, breaks free (ovulation) and floats out of the ovary (Figs. 2.2 and
2.3). Some of the cumulus oophorus cells then rearrange themselves around
the zona pellucida to form the corona radiata (Figs. 2.4–2.6).

During ovulation, some women feel a slight pain, known as middle pain
because it normally occurs near the middle of the menstrual cycle. Ovulation
is also generally accompanied by a rise in basal temperature, which can be
monitored to aid in determining when release of the oocyte occurs. Some
women fail to ovulate because of a low concentration of gonadotropins. In
these cases, administration of an agent to stimulate gonadotropin release and
hence ovulation can be employed. Although such drugs are effective, they
often produce multiple ovulations, so that the risk of multiple pregnancies is
10 times higher in these women than in the general population.

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