Melatonin modulates granulosa cell angiogenesis differently in female- and male-factor infertility

To analyze the effects of melatonin on angiogenesis in cultured granulosa cells from women undergoing in vitro fertilization, comparing those with female-factor versus male-factor infertility. Granulosa cells were obtained from 47 women undergoing in vitro fertilization treatment, including 31 women with female-factor (FFG) and 16 women with male-factor infertility (MFG). Cells from both groups were cultured and divided into four treatment conditions for 96 h: a) control (culture medium without melatonin); b) vehicle (melatonin diluent–ethanol); c) 0.1 µM melatonin; and d) 10 µM melatonin. Expression of 84 genes involved in angiogenesis signaling pathway was analyzed by real-time PCR. Cultured granulosa cells from both groups expressed aromatase and melatonin receptors. In both groups, cell proliferation peaked at 72 h when exposed to 10 µM melatonin. Of the 84 analyzed genes, three showed significant differential mRNA expression. In the MFG, melatonin at 10 µM upregulated VEGF-B mRNA expression in granulosa cells but downregulated PDGFA and HGF mRNA expression, in contrast to the higher expression of these genes in the FFG under identical conditions. Melatonin differentially modulates angiogenesis-related gene expression in granulosa cells, indicating that its effects may depend on infertility type and melatonin dose in women undergoing in vitro fertilization.