Histopathologic changes of uterus following gossypol treatment during early pregnancy in rats

Intramuscular injections of gossypol acetic acid (25 mg in 10% EtOH/kg/day beginning on day 2 of diestrus) disrupted early pregnancy in rats as determined by light and electron microscopy. As in pregnant controls, in the uteri of treated rats increased glandular secretion, stromal hyperemia, and decidual tissue formation were noted at days 3-5 of pregnancy. At day 6, extreme hyperemia and stromal hemorrhage had occurred around well-developed decidual tissue with foci of denuded mucosal surface. There was extravasation of blood into the uterine lumen, which was absent in controls. At days 5 and 6 of pregnancy, electron microscopy revealed shorter and fewer microvilli on the uterine glandular cells in the treated versus the control uterus. Luminal epithelial cells had not undergone the normal changes of pregnancy. These results imply that gossypol administered under our conditions neither prevented nor delayed implantation and formation of decidual tissue in the rat uterine endometrium but continuing development of the endometrium was disrupted at day 6 of pregnancy. This disruption of pregnancy may have resulted from a luteolytic action by gossypol that would not permit full structural differentiation in the rat uterus after implantation.