Melatonin modulates the in vitro angiogenesis of granulosa cells collected from women with marital infertility for IVF

Abstract

Melatonin concentration is
 several folds higher in the follicular fluid than that in blood suggesting an
 important role of this molecule on follicular physiology. However, the actions
 of melatonin on angiogenesis in granulosa cells are currently unknown. In this
 study, we have specifically investigated the potential effects of melatonin on
 the angiogenesis in granulosa cells from female individuals with marital
 infertility. Sixty patients who were submitted to the in vitrofertilization were included. The granulosa-luteal cells of these females were
 collected for cell culture. The cells were divided into four groups: a) vehicle
 (control); b) 0.1 µM melatonin; c) 1 µM melatonin; d) 10 µM melatonin treated
 groups, respectively. After a period of 10 days of culture, expression of genes
 involved in the angiogenesis signaling pathway were analyzed by Real-Time PCR
 and Western Blot assays. The results showed that the expressions of FGF1(fibroblast growth factor 1), IL1B (interleukin 1-beta), VEGFR-2(type 2 vascular-endothelial growth factor receptor), and TGFB1 (tumor
 growth factor 1- beta) were significantly upregulated in melatonin treated
 groups compared to the control. In contrast, the expressions of HIF-1A(hypoxia-inducing factor 1-alpha), FGF2 (fibroblastic growth factor 2), IGF-1(insulin-like growth factor 1), and VEGFA (vascular endothelial growth
 factor alpha) were significantly downregulated by melatonin compared to the
 control. The results suggest that melatonin modulates angiogenesis of granulosa
 cells from women with marital infertility. The underlining mechanism may relate
 to melatonin maintaining the homeostasis of VEGF, especially at a low dose of
 melatonin.