Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China; Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China; Fujian Provincial Key Laboratory of Reproductive Health Research, Medical College of Xiamen University, Xiamen, Fujian 361102, China.
Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China.
J Steroid Biochem Mol Biol. 2023 Oct;233:106372. doi: 10.1016/j.jsbmb.2023.106372. Epub 2023 Aug 2.
TGF-β superfamily has long been demonstrated to be essential for folliculogenesis and luteinization. Forkhead box G1 (FOXG1, also known as BF1), a member of the FOX family and an inhibitor of TGF-β signaling pathway, is a nucleocytoplasmic transcription factor that is essential for forebrain development. FOXG1 is involved in neurodevelopment and cancer pathology, however, little is known about the role of FOXG1 in reproduction. In this study, the spatiotemporal expression pattern of FOXG1 was examined during early mouse oocyte and embryonic development and its role during corpora luteum (CL) formation was further elucidated. The results showed that FOXG1 is localized in oocytes, theca cells (TCs) and CLs. After fertilization, FOXG1 is expressed at all stages during early embryogenesis, from zygotes to blastocysts. Following gonadotropin administration in immature mice, the expression of Foxg1 significantly increased along with steroidogenic genes, including Star, Hsd3β, Cyp11a1, as well as Cyp17a1 and Cyp19a1. The latter two first increased after pregnant mare serum gonadotropin stimulation, then decreased in response to hCG treatment. In addition, silencing of Foxg1 significantly reduced the concentration of testosterone and estrogen in cultured primary granulosa cells (GCs) and TCs (P < 0.05). Mechanistic studies demonstrated that the expression level of genes that are critical in estrogen synthesis were significantly reduced after Foxg1 silencing, including Cyp17a1 and Cyp19a1. In conclusion, FOXG1 is expressed in a stage-specific manner during folliculogenesis and embryogenesis and exerts a regulatory influence on testosterone and estrogen synthesis.
TGF-β 超家族长期以来被证明对卵泡发生和黄体化至关重要。叉头框 G1（FOXG1，也称为 BF1）是 FOX 家族的成员，也是 TGF-β 信号通路的抑制剂，是一种核质转录因子，对前脑发育至关重要。FOXG1 参与神经发育和癌症病理学，但关于 FOXG1 在生殖中的作用知之甚少。在这项研究中，研究了 FOXG1 在早期小鼠卵母细胞和胚胎发育过程中的时空表达模式，并进一步阐明了其在黄体（CL）形成中的作用。结果表明，FOXG1 定位于卵母细胞、卵泡膜细胞（TCs）和 CLs。受精后，FOXG1 在早期胚胎发生的所有阶段都有表达，从受精卵到囊胚。在未成熟小鼠中给予促性腺激素后，Foxg1 的表达随着类固醇生成基因的表达显著增加，包括 Star、Hsd3β、Cyp11a1 以及 Cyp17a1 和 Cyp19a1。后两者在孕马血清促性腺激素刺激后首先增加，然后在 hCG 处理时减少。此外，沉默 Foxg1 显著降低了培养的初级颗粒细胞（GCs）和 TCs 中的睾酮和雌激素浓度（P<0.05）。机制研究表明，沉默 Foxg1 后，雌激素合成关键基因的表达水平显著降低，包括 Cyp17a1 和 Cyp19a1。总之，FOXG1 在卵泡发生和胚胎发生过程中以特定阶段的方式表达，并对睾酮和雌激素合成发挥调节作用。
