Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA.
Department of Histology and Embryology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Biol Reprod. 2022 Oct 11;107(4):977-983. doi: 10.1093/biolre/ioac140.
The Notch signaling pathway is required for reproductive success. This pathway activates its transcriptional effector, recombination signal binding protein for immunoglobulin kappa J (Rbpj), to induce transcription of its target genes. This signaling pathway is required for successful decidualization, implantation, and uterine repair following parturition. To identify the compartmental specific roles of the Notch signaling pathway in the establishment of pregnancy, we generated epithelial and decidual stromal cell specific knockouts of Rbpj utilizing lactoferrin iCre and Prl8A2 iCre, respectively. Both conditional knockout mouse models were fertile. The Rbpj epithelial knockout mice displayed 27% resorption sites at E15.5, but this did not significantly impact the number of live born pups compared with controls. In addition, the Rbpj epithelial knockout mice displayed increased estrogen signaling in their stromal compartment. Given that both mouse models exhibited fertility comparable to control animals, the epithelial and stromal specific nature of the iCre recombinases utilized, and previously published Rbpj total uterine knockout mouse models, we conclude that Notch effector Rbpj signaling is required at the initiation of pregnancy to support decidualization in stromal cells, but that Rbpj is not required in the epithelial compartment nor is it required for post-implantation pregnancy success.
Notch 信号通路对于生殖成功是必需的。该通路激活其转录效应因子,免疫球蛋白 kappa J 重组信号结合蛋白(Rbpj),以诱导其靶基因的转录。该信号通路对于产后成功的蜕膜化、着床和子宫修复是必需的。为了确定 Notch 信号通路在妊娠建立中的特定区域作用,我们分别利用乳铁蛋白 iCre 和 Prl8A2 iCre 生成了上皮和蜕膜基质细胞特异性的 Rbpj 敲除小鼠模型。这两种条件性敲除小鼠模型均具有生育能力。Rbpj 上皮细胞敲除小鼠在 E15.5 时出现 27%的吸收部位,但与对照组相比,这并未显著影响活产幼鼠的数量。此外,Rbpj 上皮细胞敲除小鼠的基质细胞中雌激素信号增强。鉴于这两种小鼠模型的生育能力与对照动物相当,iCre 重组酶的上皮和基质特异性利用,以及之前发表的 Rbpj 全子宫敲除小鼠模型,我们得出结论,Notch 效应器 Rbpj 信号在妊娠起始时是必需的,以支持基质细胞的蜕膜化,但上皮细胞中 Rbpj 不是必需的,也不是着床后妊娠成功所必需的。