The effect of the angiogenesis inhibitor TNP-470 on luteal establishment and function in the primate

Angiogenesis during luteal development is probably essential for normal lut ein cell function. Since the angiogenesis inhibitor TNP-470 inhibits pregna ncy in mice, the current study investigated its effects on the establishmen t and function of the primate corpus luteum, Regularly ovulating macaques w ere treated with TNP-470 (6 mg/kg), i.v. in three doses, 48 h apart. Serum progesterone concentrations, as indicators of treatment effect, were normal in four macaques where treatment commenced at the onset of the ovulatory p rogesterone rise, and in five of eight in which treatment commenced a few d ays before ovulation. In the other three the normal progesterone rise was a bsent. To investigate the direct effect on luteal angiogenesis of a daily d ose over a longer period, four marmosets received 18 mg/kg/day of TNP-470 i .v. for 9 days starting at ovulation. On day 10, luteal cell proliferation tvas determined by nuclear bromodeoxyuridine incorporation. Luteal microvas culature was examined using immunocytochemical factor VIII staining, and en dothelial cell and luteal function assessed by in-situ hybridization of ins ulin-like growth factor binding protein-3 mRNA and plasma progesterone conc entrations respectively. None of these parameters were affected by the TNP- 470 treatment. The results show that, with the treatment regimens employed, TNP-470 had no significant effect on the expression of the differentiated state of the primate corpus luteum.