Ovarian follicles are exposed to stressors such as higher levels of non-esterified free fatty acids (NEFAs) or hypoxia. High follicular levels of NEFA severely affect granulosa cells (GCs) by targeting key genes of estradiol biosynthesis. Cultured GCs exposed to hypoxia showed specific regulation of genes that initiate luteinization. These effects were partly mediated by hypoxia inducible factor1 (HIF1). Thus, ovarian follicles are susceptible to elevated NEFA levels, but cope up with severe hypoxia prevailing during late folliculogenesis through specific transcription factors such as HIF1.<eng>
