Language

English

Publication Date

4-18-2025

Journal

Science Advances

DOI

10.1126/sciadv.adt6113

PMID

40249812

PMCID

PMC12007591

PubMedCentral® Posted Date

4-18-2025

PubMedCentral® Full Text Version

Post-print

Abstract

More than 60% of pregnancy losses occur during the first trimester, highlighting the need to understand the role of the oviduct in early pregnancy. In this study, we conditionally ablated the classical progesterone receptor (Pgr) in oviductal epithelial cells, called the Pgrd/d mouse model. We found that 40% of embryos collected from Pgrd/d females were nonviable or developmentally delayed, indicating that epithelial PGR expression is crucial for embryonic development. Single-cell RNA sequencing revealed up-regulation of proinflammatory genes, including interleukin-22 (IL-22), in the epithelial cells of Pgrd/d females. Pharmacological inhibition of inflammation using nonsteroidal anti-inflammatory drugs significantly reduced IL-22 levels in the oviducts and rescued embryonic developmental rates in Pgrd/d females. Coculture of wild-type zygotes with IL-22 significantly decreased the number of expanded blastocysts. Our findings suggest that progesterone signaling is vital for immunoregulation and normal preimplantation development, potentially providing insights for developing diagnostic tools and therapeutic strategies to address pregnancy failures.

Keywords

Animals, Female, Progesterone, Epithelial Cells, Mice, Embryonic Development, Signal Transduction, Receptors, Progesterone, Pregnancy, Blastocyst, Oviducts, Interleukins, Interleukin-22, Fallopian Tubes

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.