Abstract
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.
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ACKNOWLEDGMENTS
The work was performed using the equipment of the Core Centrum (Koltsov Institute of Developmental Biology, Russian Academy of Sciences) and the Center for Collective Use (Moscow State University).
Funding
The work was performed within the framework of 2020 State Assignment of Koltzov Institute of Developmental Biology of Russian Academy of Sciences, no. 0108-2019-0003. The study into the effects of fluoxetine was carried out with the financial support of the Russian Science Foundation, project no. 18-74-00143.
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D.A. Nikishin invented and designed the experiments, analyzed the data, and wrote the article. Y.V. Khramova and L.A. Malchenko performed cell culture work and set up experiments. N.M. Alyoshina performed a molecular genetic analysis. Y.B. Shmukler supervised the study and participated in the preparation of the text.
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Statement on the welfare of animals. In this study, all manipulations performed with experimental animals and methods of anesthesia, euthanasia, and animal care before and after experimental interventions were in accordance with international standards on bioethics.
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Nikishin, D.A., Khramova, Y.V., Alyoshina, N.M. et al. Oocyte-Mediated Effect of Serotonin on the Functional Status of Granulosa Cells. Russ J Dev Biol 52, 97–104 (2021). https://doi.org/10.1134/S1062360421020065
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DOI: https://doi.org/10.1134/S1062360421020065