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Publication : Cooperative effects of oocytes and estrogen on the forkhead box L2 expression in mural granulosa cells in mice.

First Author  Ito H Year  2022
Journal  Sci Rep Volume  12
Issue  1 Pages  20158
PubMed ID  36424497 Mgi Jnum  J:331726
Mgi Id  MGI:7387736 Doi  10.1038/s41598-022-24680-x
Citation  Ito H, et al. (2022) Cooperative effects of oocytes and estrogen on the forkhead box L2 expression in mural granulosa cells in mice. Sci Rep 12(1):20158
abstractText  Forkhead box L2 (FOXL2) plays a critical role in the development and function of mammalian ovaries. In fact, the causative effects of FOXL2 misregulations have been identified in many ovarian diseases, such as primary ovarian insufficiency and granulosa cell tumor; however, the mechanism by which FOXL2 expression is regulated is not well studied. Here, we showed that FOXL2 expression in ovarian mural granulosa cells (MGCs) requires stimulation by both oocyte-derived signals and estrogen in mice. In the absence of oocytes or estrogen, expression of FOXL2 and its transcriptional targets, Cyp19a1 and Fst mRNA, in MGCs were significantly decreased. Moreover, expression levels of Sox9 mRNA, but not SOX9 protein, were significantly increased in the FOXL2-reduced MGCs. FOXL2 expression in MGCs was maintained with either oocytes or recombinant proteins of oocyte-derived paracrine factors, BMP15 and GDF9, together with estrogen, and this oocyte effect was abrogated with an ALK5 inhibitor, SB431542. In addition, the FOXL2 level was significantly decreased in MGCs isolated from Bmp15(-/-) /Gdf9(+/-) mice. Therefore, oocyte, probably with estrogen, plays a critical role in the regulation of FOXL2 expression in mural granulosa cells in mice.
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