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子宫内膜容受性和着床需要子宫内 BMP 信号通过 ACVR2A-SMAD1/SMAD5 轴。

Endometrial receptivity and implantation require uterine BMP signaling through an ACVR2A-SMAD1/SMAD5 axis.

机构信息

Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.

Center for Drug Discovery, Baylor College of Medicine, Houston, TX, USA.

出版信息

Nat Commun. 2021 Jun 7;12(1):3386. doi: 10.1038/s41467-021-23571-5.

DOI:10.1038/s41467-021-23571-5
PMID:34099644
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8184938/
Abstract

During early pregnancy in the mouse, nidatory estrogen (E2) stimulates endometrial receptivity by activating a network of signaling pathways that is not yet fully characterized. Here, we report that bone morphogenetic proteins (BMPs) control endometrial receptivity via a conserved activin receptor type 2 A (ACVR2A) and SMAD1/5 signaling pathway. Mice were generated to contain single or double conditional deletion of SMAD1/5 and ACVR2A/ACVR2B receptors using progesterone receptor (PR)-cre. Female mice with SMAD1/5 deletion display endometrial defects that result in the development of cystic endometrial glands, a hyperproliferative endometrial epithelium during the window of implantation, and impaired apicobasal transformation that prevents embryo implantation and leads to infertility. Analysis of Acvr2a-PRcre and Acvr2b-PRcre pregnant mice determined that BMP signaling occurs via ACVR2A and that ACVR2B is dispensable during embryo implantation. Therefore, BMPs signal through a conserved endometrial ACVR2A/SMAD1/5 pathway that promotes endometrial receptivity during embryo implantation.

摘要

在小鼠的早期妊娠中，滋养层雌激素（E2）通过激活尚未完全表征的信号通路网络来刺激子宫内膜容受性。在这里，我们报告说骨形态发生蛋白（BMPs）通过保守的激活素受体类型 2A（ACVR2A）和 SMAD1/5 信号通路来控制子宫内膜容受性。使用孕激素受体（PR）-cre 生成了包含单个或双条件缺失 SMAD1/5 和 ACVR2A/ACVR2B 受体的小鼠。SMAD1/5 缺失的雌性小鼠表现出子宫内膜缺陷，导致囊状子宫内膜腺体的发育、着床窗口期间的子宫内膜过度增殖以及顶端基底转化受损，从而阻止胚胎着床并导致不孕。对 Acvr2a-PRcre 和 Acvr2b-PRcre 怀孕小鼠的分析确定，BMP 信号通过 ACVR2A 发生，并且在胚胎着床期间 ACVR2B 是可有可无的。因此，BMP 通过保守的子宫内膜 ACVR2A/SMAD1/5 通路信号传递，促进胚胎着床期间的子宫内膜容受性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfec/8184938/3b3209910298/41467_2021_23571_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfec/8184938/285db8017723/41467_2021_23571_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfec/8184938/25587fc733e2/41467_2021_23571_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfec/8184938/40de60f37ba4/41467_2021_23571_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfec/8184938/d68aebe140f7/41467_2021_23571_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfec/8184938/05615dac431e/41467_2021_23571_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfec/8184938/3b3209910298/41467_2021_23571_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfec/8184938/285db8017723/41467_2021_23571_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfec/8184938/25587fc733e2/41467_2021_23571_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfec/8184938/40de60f37ba4/41467_2021_23571_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfec/8184938/d68aebe140f7/41467_2021_23571_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfec/8184938/05615dac431e/41467_2021_23571_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfec/8184938/3b3209910298/41467_2021_23571_Fig6_HTML.jpg

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