Tan Xue, Zhang Lingling, Li Tianqi, Zhan Jianmin, Qiao Kun, Wu Haili, Sun Shenfei, Huang Meina, Zhang Fangxi, Zhang Meixing, Li Changwei, Li Runsheng, Pan Hongjie
National Health Commission (NHC) Key Laboratory of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, School of Pharmacy, Fudan University, Shanghai, China.
Center for Reproductive Medicine, Tenth People's Hospital of Tongji University, Shanghai, China.
Front Cell Dev Biol. 2021 Sep 24;9:666303. doi: 10.3389/fcell.2021.666303. eCollection 2021.
The WNT signaling pathway plays a crucial role in oviduct/fallopian development. However, the specific physiological processes regulated by the WNT pathway in the fallopian/oviduct function remain obscure. Benefiting from the knockout mouse model, we report the regulation of oviduct epithelial secretion by LGR4. Specifically, the loss of altered the mouse oviduct size and weight, severely reduced the number of oviductal epithelial cells, and ultimately impaired the epithelial secretion. These alterations were mediated by a failure of CTNNB1 protein accumulation in the oviductal epithelial cytoplasm, by the modulation of WNT pathways, and subsequently by a profound change of the gene expression profile of epithelial cells. In addition, selective activation of the WNT pathway triggered the expression of steroidogenic genes, like and β-, through the activation of the transcriptional factor NR5A2 in an oviduct primary cell culture system. As demonstrated, the LGR4 protein modulates a WNT-NR5A2 signaling cascade facilitating epithelial secretory cell maturation and steroidogenesis to safeguard oviduct development and function in mice.
WNT信号通路在输卵管/输卵管发育中起着至关重要的作用。然而,WNT通路在输卵管/输卵管功能中调节的具体生理过程仍不清楚。受益于基因敲除小鼠模型,我们报道了LGR4对输卵管上皮分泌的调节作用。具体而言,LGR4缺失改变了小鼠输卵管的大小和重量,严重减少了输卵管上皮细胞的数量,并最终损害了上皮分泌功能。这些改变是由CTNNB1蛋白在输卵管上皮细胞质中积累失败介导的,通过WNT通路的调节,随后上皮细胞基因表达谱发生了深刻变化。此外,在输卵管原代细胞培养系统中,WNT通路的选择性激活通过激活转录因子NR5A2触发了类固醇生成基因(如和β-)的表达。结果表明,LGR4蛋白调节WNT-NR5A2信号级联反应,促进上皮分泌细胞成熟和类固醇生成,以保障小鼠输卵管的发育和功能。