Histological examination of the rat ovarian follicle wall prior to ovulation

Abstract

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 hr after the administration of HCG (human chorionic gonadotropin) 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 larger 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 antiinflammatory drugs aspirin, salicylate, and indomethacin inhibited ovulation in immature rats when administered in antiinflammatory dosages shortly before the expected time of ovulation. The inhibition was observed in animals superovulated by exogenous phenazine methosulphate (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.