Document Type

Article

Publication Date

6-7-2021

Publication Title

Nat Commun

Keywords

JGM, Activin Receptors, Type II, Animals, Biopsy, Bone Morphogenetic Proteins, Disease Models, Animal, Embryo Implantation, Endometrium, Estrogens, Female, Humans, Infertility, Female, Mice, Mice, Knockout, Pregnancy, Signal Transduction, Smad1 Protein, Smad5 Protein

JAX Source

Nat Commun 2021 Jun 7; 12(1):3386

Volume

12

Issue

1

First Page

3386

Last Page

3386

ISSN

2041-1723

PMID

34099644

DOI

https://doi.org/10.1038/s41467-021-23571-5

Grant

AR060636

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.

Comments

This article is licensed under a Creative Commons Attribution 4.0 International License.

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