| Summary: | We aimed to determine whether a functional link with impact on female ovarian reserve exists between <i>FMR1</i> expression and expression ratios of AKT/mTOR signaling genes in human granulosa cells in vivo, as suggested from prior in vitro data. Three hundred and nine women, who were classified as normal (NOR; <i>n</i> = 225) and poor (POR; <i>n</i> = 84) responders based on their ovarian reserve, were recruited during stimulation for assisted reproductive techniques. Expressions of <i>FMR1</i> and of key genes of the AKT/mTOR and AKT/FOXO1/3 signaling pathways were comparatively analyzed in their granulosa cells. <i>FMR1</i> expression in granulosa cells of NOR and POR correlated significantly with <i>AKT1, TSC2, mTOR,</i> and <i>S6K</i> expression. No correlation was found between <i>FMR1</i> and <i>FOXO1</i> in all, and <i>FOXO3</i> expression in POR, patients. <i>AKT1</i> expression was significantly higher and <i>FOXO1</i> expression lower in POR samples, whereas <i>AKT1</i> expression was lower and <i>FOXO1</i> expression was higher in NOR samples. In human native granulosa cells, <i>FMR1</i> expression significantly correlated with the expression of key genes of the AKT/mTOR signaling pathway, but not with the FOXO1/3 signaling pathway. Our data point to a functional link between <i>FMR1</i> expression and expression of the AKT/mTOR signaling pathway genes controlling human follicular maturation.
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