Zhang Yaqi, Guo Zeyuan, Du Zhangsheng, Yao Zhichao, Guo Tong, Cheng Yin, Wang Kai, Ma Xiaoyan, Chen Chunlu, Kebreab Ermias, Wang Dong, Lyu Lihua
College of Animal Science, Shanxi Agricultural University, Taigu, Shanxi, China.
College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, China.
Mol Reprod Dev. 2023 Mar;90(3):153-165. doi: 10.1002/mrd.23674. Epub 2023 Feb 12.
Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) regulates mammalian ovarian follicle growth and maturation; however, its effect on luteinized granulosa cells (LGCs) in sheep ovarian follicles remains unknown. Here we explored the regulatory role of LGC functions and steroid hormone synthesis by BAMBI. Multiple sequence alignment revealed that the sheep BAMBI gene sequence was relatively conserved. Sheep LGCs were strongly positive for BAMBI. LGC proliferation increased when BAMBI was silenced and decreased when BAMBI was overexpressed. After BAMBI overexpression, the expression of CASP3, CASP8, CASP9, and BAX significantly increased, whereas that of BCL2 and the ratio of BCL2/BAX expression decreased. The opposite was observed after BAMBI silencing. CDKN1A, CCND1, and CCND2 were downregulated with BAMBI overexpression and upregulated with BAMBI silencing. Expression of steroid hormone-related genes (CYP11A1, STAR, and 3BHSD), except CYP19A1, significantly increased after BAMBI overexpression. Moreover, estrogen and progesterone secretion increased after BAMBI overexpression and decreased after BAMBI interference. The effect of the exogenous addition of bone morphogenetic protein 2 (BMP2) on GCs was similar to that of BAMBI overexpression. In conclusion, BAMBI can regulate the proliferation and steroid hormone synthesis of sheep LGCs, and BMP2 can affect LGCs as an activator of BAMBI. These findings provide a basis for further research on the physiological role of BAMBI.
骨形态发生蛋白与激活素膜结合抑制剂（BAMBI）调节哺乳动物卵巢卵泡的生长和成熟；然而，其对绵羊卵巢卵泡中黄素化颗粒细胞（LGCs）的影响尚不清楚。在此，我们探讨了BAMBI对LGC功能和类固醇激素合成的调节作用。多序列比对显示绵羊BAMBI基因序列相对保守。绵羊LGCs对BAMBI呈强阳性。BAMBI沉默时LGC增殖增加，BAMBI过表达时LGC增殖减少。BAMBI过表达后，CASP3、CASP8、CASP9和BAX的表达显著增加，而BCL2的表达及BCL2/BAX表达比值降低。BAMBI沉默后观察到相反的结果。BAMBI过表达时CDKN1A、CCND1和CCND2下调，BAMBI沉默时上调。除CYP19A1外，BAMBI过表达后类固醇激素相关基因（CYP11A1、STAR和3BHSD）的表达显著增加。此外，BAMBI过表达后雌激素和孕酮分泌增加，BAMBI干扰后减少。外源性添加骨形态发生蛋白2（BMP2）对颗粒细胞的影响与BAMBI过表达相似。总之，BAMBI可调节绵羊LGCs的增殖和类固醇激素合成，BMP2可作为BAMBI的激活剂影响LGCs。这些发现为进一步研究BAMBI的生理作用提供了依据。
