Effect of vaginally administered fumagillin on the morphology of implantation stage endometrium in the rhesus monkey

Intravaginal administration of an anti-angiogenic agent, fumagillin, during blastocyst implantation, inhibits pregnancy establishment in a dose-related manner in the rhesus monkey. In the present study, mated female rhesus monkeys were vaginally inserted with tampons containing vehicle (group 1; n = 5) and test agent (fumagillin, 4 mg/animal; group 2; n = 6) on cycle day 20, and endometrial tissue samples were collected on cycle day 24 from all monkeys and processed for morphometric and ultrastructural analysis. Concentrations of estradiol-17beta, progesterone and chorionic gonadotrophin in peripheral circulation were determined. From serum profiles of hormones, two monkeys in group 1, and one animal in group 2 appeared pregnant. Endometrial morphology revealed histologic evidence of pregnancy in three of six fumagillin-treated animals, while other three fumagillin-treated animals showed degenerative changes in glands and venules along with marked extravasation. It is possible that the function of corpus luteum was affected by fumagillin treatment resulting in inadequate progesterone production (p <0.05), and consequent inadequate endometrial secretory preparation and receptivity, as revealed from decline in apical movement of vacuoles (p <0.05) and increase (p <0.05) in extravasation of red cells and leukocytes.