Effect of fibroblast growth factor signaling on cumulus expansion in mice in vitro
Effect of fibroblast growth factor signaling on cumulus expansion in mice in vitro
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成纤维细胞生长因子信号传导对体外小鼠卵丘扩张的影响
DOI：
10.1002/mrd.23616
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发表时间：
2022
影响因子：
2.5
通讯作者：
Sugiura Koji
中科院分区：
文献类型：
--
作者：
Kanke Takuya;Fujii Wataru;Naito Kunihiko;Sugiura Koji
卵母细胞伴发的卵丘细胞扩张是正常哺乳动物排卵中的一种基本现象。事实上，卵丘扩展相关基因，包括Has2、Ptgs2、Ptx3和Tnfaip6的表达减弱，会导致排卵失败，导致女性不育或不育。此外，新的证据表明，卵泡内产生的成纤维细胞生长因子家族的蛋白调节卵丘细胞的发育和功能；然而，成纤维细胞生长因子信号对卵丘扩大的影响尚未得到广泛的研究。在此，我们研究了成纤维细胞生长因子信号，尤其是卵母细胞分泌的成纤维细胞生长因子8在表皮生长因子诱导的小鼠卵丘扩张中的作用。成纤维细胞生长因子受体抑制剂NVP-BGJ398可显著降低卵丘-卵母细胞复合体(COCs)内成纤维细胞信号转导因子MAPK3/1的磷酸化水平。此外，尽管NVP-BGJ398处理不影响卵丘细胞的扩张，但它显著上调了Ptgs2和Ptx3的表达。相反，重组FGF8处理不影响卵丘的扩张程度，也不影响COCs或去卵细胞的卵丘细胞复合体中扩张相关基因的表达。综上所述，这些结果表明，除FGF8外，FGFs对小鼠的卵丘扩张过程具有抑制作用。
The expansion of cumulus cells associated with oocytes is an essential phenomenon in normal mammalian ovulation. Indeed, attenuated expression of cumulus expansion‐related genes, includingHas2,Ptgs2,Ptx3, andTnfaip6, results in ovulation failure, leading to female subfertility or infertility. Moreover, emerging evidence suggests that proteins of the fibroblast growth factor (FGF) family, produced within ovarian follicles, regulate the development and function of cumulus cells; however, the effects of FGF signaling on cumulus expansion have not been investigated extensively. Herein, we investigate the effects of FGF signaling, particularly those of FGF8 secreted by oocytes, on epidermal growth factor‐induced cumulus expansion in mice. The phosphorylation level of MAPK3/1, an intracellular mediator of FGF signaling, was significantly decreased in cumulus‐oocyte complexes (COCs) following treatment with NVP‐BGJ398, an FGF receptor inhibitor. Moreover, even though NVP‐BGJ398 treatment did not affect cumulus cell expansion, it significantly upregulated the expression ofPtgs2andPtx3. In contrast, treatment with recombinant FGF8 did not affect the degree of cumulus expansion or the expression of expansion‐related genes in COCs or oocytectomized cumulus cell complexes. Collectively, these results suggest that FGFs, other than FGF8, exert suppressive effects on the cumulus expansion process in mice.