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-relate d manner in the rhesus monkey. In the present study, mated female rhesus mo nkeys 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 2 0, and endometrial tissue samples were collected on cycle day 24 from all m onkeys and processed for morphometric and ultrastructural analysis. Concent rations of estradiol-17 beta, progesterone and chorionic gonadotrophin in p eripheral circulation were determined. From serum profiles of hormones, two monkeys in group 1, and one animal in group 2 appeared pregnant. Endometri al morphology revealed histologic evidence of pregnancy in three of six fum agillin-treated animals, while other three fumagillin-treated animals showe d degenerative changes in glands and venules along with marked extravasatio n. It is possible that the function of corpus luteum was affected by fumagi llin 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 inc rease (p <0.05) in extravasation of red cells and leukocytes. (C) 2001 Else vier Science Inc. All rights reserved.