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Biology of Reproduction, Vol 11, 483-503, Copyright © 1974 by Society for the Study of Reproduction
1 Laboratories of Human Reproduction and Reproductive Biology and The Departnment of
Anatomy, Harvard Medical School, 45 Shattuck Street, Boston, Massachusetts 02115 The histological changes occurring in rat ovarian follicle walls prior to ovulation were
studied by light and electron microscopy. Follicles were collected at 0, 5, 10, and 11 h
after the administration of HCG to stimulate ovulation, and also at what was judged to
be the instant before rupture from ovaries that were exteriorized in a plastic chamber
for direct observation. The earliest morphological change detected was the leakage of erythrocytes from blood vessels, and thus their presence, presumably along with plasma, in
the intercellular spaces of the follicle walls. Somewhat later, occasional theca cells died
and degenerated, and slight signs of cytolysis appeared at the surface of all cell types.
The tunica albuginea often became loose, with a large increase in the extent of extracellular
space between cells. A conspicuous feature of follicle walls near the time of ovulation
was the rounding up and detachment from the follicle wall of apparently healthy granulosa
and theca cells; at ovulation the granulosa layer was absent from the stigma. Clumps of
fibrin were commonly found in the extracellular space of the follicle wall and in follicular
fluid, as was debris from degenerating cells. The final change noted before ovulation was
the degeneration and loss of peritoneal epithelial cells. No collagen could be detected in
follicle walls at any time. The early leakage of erythrocytes from blood vessels and the common occurrence of
fibrin in the intercellular space and follicular fluid suggested that an acute inflammatory
reaction may be involved in the formation and rupture of the stigma. The anti-inflammatory drugs aspirin, salicylate, and indomethacin inhibited ovulation in immature rats when
administered in anti-inflammatory dosages shortly before the expected time of ovulation.
The inhibition was observed in animals superovulated by exogenous PMS and HCG, as
well as in animals ovulating spontaneously after a small dose of PMS. It is concluded that
a process which involves prostaglandin synthesis is involved in follicle rupture, and that
this step may possibly be the early vascular phase of an inflammatory response.
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