Aberrant BMP15/HIF-1α/SCF signaling pathway in human granulosa cells is involved in the PCOS related abnormal follicular development
Aberrant BMP15/HIF-1α/SCF signaling pathway in human granulosa cells is involved in the PCOS related abnormal follicular development
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DOI：
10.1080/09513590.2022.2125951
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发表时间：
2022-09
影响因子：
2
通讯作者：
Li-Yun Cao;Zhiqin Zhang;Peipei Liu;Dingfei Xu;Liang Tang;Lu Fan;Xue-Chen Sun;Jia-Yi Li;Qiongfang Wu;Zeng-ming Li;Jun Tan
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文献类型：
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作者：
Li-Yun Cao;Zhiqin Zhang;Peipei Liu;Dingfei Xu;Liang Tang;Lu Fan;Xue-Chen Sun;Jia-Yi Li;Qiongfang Wu;Zeng-ming Li;Jun Tan
摘要目的探讨SCF在PCOS相关卵泡GCs中表达的调控机制。材料与方法检测69例PCOS患者和74例正常排卵患者血清、卵泡液和GC中SCF、BMP 15和HIF-1α的水平。本研究使用KGN细胞系。结果PCOS组获卵率较高，但MII期卵母细胞和2 PN受精率较低。PCOS患者FF中BMP 15、血清和FF中SCF水平均低于正常对照组。PCOS患者胃癌组织中HIF-1α和SCF的表达均低于非PCOS患者。rhBMP-15处理后，KGN细胞中HIF-1α和SCF的表达明显增加，而BMP-1受体抑制剂DM可明显抑制rhBMP-15对KGN细胞HIF-1α和SCF表达的促进作用。此外，KGN细胞中HIF-1α表达的敲低显著降低了人GC中SCF的表达，尽管激活了BMP 15信号通路。结论BMP 15可通过上调HIF-1α的表达诱导人GCs中SCF的表达，该信号通路的异常可能参与了PCOS相关的卵泡发育异常。
Abstract Aims To investigate the regulatory mechanism of SCF expression in human GCs of PCOS related follicles. Materials and Methods SCF, BMP15 and HIF-1α were evaluated in human serums, follicular fluids (FFs) and GCs, which were collected from 69 PCOS patients and 74 normal ovulatory patients. KGN cell line was used in this study. Results Our results showed that the rate of MII oocyte and 2PN fertilization was lower in PCOS group, though PCOS patients retrieved much more oocytes. The level of BMP15 in FF and the level of SCF in serum and FF were also lower in PCOS patients. We found a weakened expression of HIF-1α and SCF in GCs from PCOS patients when compared with the non-PCOS patients. The expression of HIF-1α and SCF was significantly increased in KGN cells after treating cells with rhBMP15, however, this promotion effects of BMP15 on HIF-1α and SCF expression were obviously abolished by co-treatment with BMP-I receptor inhibitor (DM). Moreover, knock down of HIF-1α expression in KGN cells significantly reduced the expression of SCF in human GCs, in spite of activating BMP15 signaling pathway. Conclusions The present study suggest that BMP15 could induce SCF expression by up-regulating HIF-1α expression in human GCs, the aberrance of this signaling pathway might be involved in the PCOS related abnormal follicular development.