FOXG1参与了小鼠卵巢功能和胚胎发育。
FOXG1 is involved in mouse ovarian functions and embryogenesis.
发表日期:2023 Aug 01
作者:
Xingyu Yan, Linlin Hou, Cong Zhang
来源:
GENES & DEVELOPMENT
摘要:
TGF-β超家族长期以来已被证明对卵泡发生和黄体化至关重要。Forkhead盒G1(FOXG1,又称BF1),FOX家族的成员和TGF-β信号通路的抑制物,是一种必不可少的细胞核和胞质转录因子,对前脑发育至关重要。FOXG1参与神经发育和癌症病理学,然而,关于FOXG1在生殖中的作用知之甚少。本研究检查了FOXG1在早期小鼠卵母细胞和胚胎发育中的时空表达模式,并进一步阐明了其在黄体形成中的作用。结果显示,FOXG1定位于卵母细胞、Theca细胞(TCs)和黄体中。受精后,FOXG1在早期胚胎发育的所有阶段表达,从受精卵到囊胚。在未成熟小鼠中施用促性腺激素后,Foxg1的表达显著增加,伴随着类固醇合成基因的增加,包括Star、Hsd3β、Cyp11a1,以及Cyp17a1和Cyp19a1。后者在施用孕马血清促性腺激素刺激后首先增加,然后在hCG处理后下降。此外,静默Foxg1显著降低了培养的原代颗粒细胞(GCs)和TCs的睾酮和雌激素浓度(P < 0.05)。机械研究证明,在静默Foxg1后雌激素合成中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育过程中以特定阶段特异地表达,并对睾酮和雌激素合成有调节作用。版权所有 © 2023。由Elsevier Ltd 发布。
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.Copyright © 2023. Published by Elsevier Ltd.