Oocyte-Mediated Effect of Serotonin on the Functional Status of Granulosa Cells

In the mammalian ovary, serotonin has all the components necessary for its signaling function and affects the functional activity of granulosa cells. At the same time, the accumulation of serotonin with the help of a specific SERT transporter occurs mainly in the oocytes of growing ovarian follicles and is hardly present in granulosa cells. Quantitative analysis of mRNA expression of markers of proliferation, apoptosis, and functional state of follicular cells, as well as oocyte growth factors, was performed on an experimental model of ovarian follicle culture. Serotonin (1 µM) does not exhibit pronounced mitogenic and pro- and antiapoptotic properties and does not affect the expression of steroidogenesis markers. At the same time, serotonin stimulates the expression of cyclin genes Ccnd1, Ccnd2, and Ccne1 and also Has2, Ptgs2, Ptgfr, Igfbp, and Ihh in granulosa cells. Also, the addition of serotonin leads to an increase in the expression of Gdf9 in oocytes. There is a more pronounced effect of serotonin compared to the primary culture of granulosa cells, which in all cases, with the exception of cyclins, is canceled by fluoxetine (10 µM). The results obtained indicate that the functional activity of granulosa cells is regulated by serotonin through its effect on the oocyte and is mediated by SERT activity.