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Notch 效应器重组信号结合蛋白对于免疫球蛋白 κJ 信号转导是子宫内膜基质细胞蜕膜化起始所必需的†。

Notch effector recombination signal binding protein for immunoglobulin kappa J signaling is required for the initiation of endometrial stromal cell decidualization†.

机构信息

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.

出版信息

Biol Reprod. 2022 Oct 11;107(4):977-983. doi: 10.1093/biolre/ioac140.

DOI:10.1093/biolre/ioac140
PMID:35835555
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9562121/
Abstract

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.

摘要

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。

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Notch effector recombination signal binding protein for immunoglobulin kappa J signaling is required for the initiation of endometrial stromal cell decidualization†.Notch 效应器重组信号结合蛋白对于免疫球蛋白 κJ 信号转导是子宫内膜基质细胞蜕膜化起始所必需的†。
Biol Reprod. 2022 Oct 11;107(4):977-983. doi: 10.1093/biolre/ioac140.
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本文引用的文献

1
Inserting Cre recombinase into the Prolactin 8a2 gene for decidua-specific recombination in mice.将 Cre 重组酶插入催乳素 8a2 基因中,以实现小鼠蜕膜特异性重组。
Genesis. 2022 May;60(4-5):e23473. doi: 10.1002/dvg.23473. Epub 2022 Apr 27.
2
Notch signaling in reproduction.Notch 信号在生殖中的作用。
Trends Endocrinol Metab. 2021 Dec;32(12):1044-1057. doi: 10.1016/j.tem.2021.08.002. Epub 2021 Sep 1.
3
Physiologic Events of Embryo Implantation and Decidualization in Human and Non-Human Primates.人类和非人类灵长类动物胚胎着床和蜕膜化的生理事件。
Int J Mol Sci. 2020 Mar 13;21(6):1973. doi: 10.3390/ijms21061973.
4
Progesterone and Estrogen Signaling in the Endometrium: What Goes Wrong in Endometriosis?子宫内膜中孕激素和雌激素信号转导:子宫内膜异位症中哪里出了问题?
Int J Mol Sci. 2019 Aug 5;20(15):3822. doi: 10.3390/ijms20153822.
5
The Notch Family Transcription Factor, RBPJκ, Modulates Glucose Transporter and Ovarian Steroid Hormone Receptor Expression During Decidualization.Notch家族转录因子RBPJκ在蜕膜化过程中调节葡萄糖转运蛋白和卵巢甾体激素受体的表达。
Reprod Sci. 2019 Jun;26(6):774-784. doi: 10.1177/1933719118799209. Epub 2018 Sep 13.
6
RBPJ mediates uterine repair in the mouse and is reduced in women with recurrent pregnancy loss.RBPJ 介导小鼠的子宫修复,在反复妊娠丢失的女性中减少。
FASEB J. 2018 May;32(5):2452-2466. doi: 10.1096/fj.201701032R. Epub 2018 Jan 8.
7
Aberrant activation of canonical Notch1 signaling in the mouse uterus decreases progesterone receptor by hypermethylation and leads to infertility.小鼠子宫中经典Notch1信号通路的异常激活通过高甲基化降低孕激素受体水平并导致不孕。
Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2300-5. doi: 10.1073/pnas.1520441113. Epub 2016 Feb 8.
8
Identification of target genes for a prolactin family paralog in mouse decidua.小鼠蜕膜中催乳素家族旁系同源基因的靶基因鉴定。
Reproduction. 2015 Jun;149(6):625-32. doi: 10.1530/REP-15-0107.
9
Decreased Notch pathway signaling in the endometrium of women with endometriosis impairs decidualization.子宫内膜异位症女性子宫内膜中Notch信号通路信号减少会损害蜕膜化过程。
J Clin Endocrinol Metab. 2015 Mar;100(3):E433-42. doi: 10.1210/jc.2014-3720. Epub 2014 Dec 29.
10
Cyclic decidualization of the human endometrium in reproductive health and failure.人类子宫内膜的周期性蜕膜化在生殖健康和失败中的作用。
Endocr Rev. 2014 Dec;35(6):851-905. doi: 10.1210/er.2014-1045. Epub 2014 Aug 20.