University of Oulu

Monsivais, D., Nagashima, T., Prunskaite-Hyyryläinen, R. et al. Endometrial receptivity and implantation require uterine BMP signaling through an ACVR2A-SMAD1/SMAD5 axis. Nat Commun 12, 3386 (2021).

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

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Author: Monsivais, Diana1,2; Nagashima, Takashi1; Prunskaite-Hyyryläinen, Renata3;
Organizations: 1Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA
2Center for Drug Discovery, Baylor College of Medicine, Houston, TX, USA
3Faculty of Biochemistry and Medicine, University of Oulu, Oulu, Finland
4Research Institute for Microbial Disease, Osaka University, Osaka, Japan
5Department of Medicine, Baylor College of Medicine, Houston, TX, USA
6Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC, USA
7Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
8National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
9Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
10University of Connecticut School of Medicine, Department of Genetics and Genome Sciences, Farmington, CT, USA
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 17.7 MB)
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Language: English
Published: Springer Nature, 2021
Publish Date: 2021-09-22


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.

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Series: Nature communications
ISSN: 2041-1723
ISSN-E: 2041-1723
ISSN-L: 2041-1723
Volume: 12
Issue: 1
Article number: 3386
DOI: 10.1038/s41467-021-23571-5
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
1184 Genetics, developmental biology, physiology
Funding: Studies were supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development grants K99/R00-HD096057 (to D.M.) and R01-HD032067 (to M.M.M.), NIH grant R01-AR060636 (to S.L.), NIH grant CA125123 (to C.J.C.) and the National Institute of Environmental Health Sciences (to F.J.D.). Diana Monsivais, Ph.D. holds a Postdoctoral Enrichment Program Award from the Burroughs Wellcome Fund.
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