Vascular endothelial growth factor and leptin: regulation in human cumulus cells and in follicles

The factors that determine oocyte competency are poorly understood. It is believed that angiogenic factors are crucial. Modulation of these factors is therefore a central consideration. The adjacent association of cumulus cells to oocytes gives these cells a particular importance in relation to oocyte behavior. We report the effects of gonadotropins on the secretion of VEGF and leptin from cumulus cells; and the concentrations of the proteins in follicular fluid and their relationship to fertilization of oocytes in vitro.

The subjects were women undergoing intracytoplasmic sperm injection (ICSI). Oocytes and follicular fluid were collected. Leptin and vascular endothelial growth factor (VEGF) concentrations in incubation supernatants and follicular fluid and leptin in cell lysates were measured. Fertilization of corresponding oocytes were noted. In the present study, cells from individual follicles were incubated, as well as pooled cells from a woman.

For the first time we demonstrated that VEGF release by human cumulus cells was modulated by gonadotropins in a dose-related, time-dependent manner, but no leptin was detected in either the supernatants after cumulus cell incubations or in cell lysates. Mean leptin levels were similar whether from follicles associated with eggs that were fertilized (14.4 +/- 1.1 ng/ml, mean +/- SEM) or not (12.4 +/- 1.1 ng/ml). Mean VEGF levels were also similar (11.1 +/- 1.2 ng/ml; 12.8 +/- 1.3 ng/ml). A greater proportion of VEGF in follicles was derived from follicular activities, compared with transfer from other physiological compartments, than leptin.

Whereas it is possible that VEGF is part of the gonadotropin-mediated network that regulates development of the oocyte, leptin may not be produced in significant quantities by cumulus cells or be related to oocyte competency.