Endometrial receptivity and implantation require uterine BMP signaling through an ACVR2A-SMAD1/SMAD5 axis
Monsivais, Diana; Nagashima, Takashi; Prunskaite-Hyyryläinen, Renata; Nozawa, Kaori; Shimada, Keisuke; Tang, Suni; Hamor, Clark; Agno, Julio E.; Chen, Fengju; Masand, Ramya P.; Young, Steven L.; Creighton, Chad J.; DeMayo, Francesco J.; Ikawa, Masahito; Lee, Se-Jin; Matzuk, Martin M (2021-06-07)
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). https://doi.org/10.1038/s41467-021-23571-5
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https://urn.fi/URN:NBN:fi-fe2021092246784
Tiivistelmä
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.
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