(252) Epigenetic Regulation of Progesterone Receptor-B in the Endometrium during Luteolysis in Sheep

Joe  A. Arosh¹, Sudipta Dutta¹, Jennifer Fridley²,  Sakhila K Banu¹

 
¹Reproductive  Endocrinology and Cell Signaling Laboratory, Department of Veterinary Integrative Biosciences. ² Veterinary Medical Park and Large Animal Clinical Sciences. College of Veterinary Medicine and Biomedical Sciences. Texas A&M University, College Station, Texas 77844.

Abstract Text: It is well understood that loss of Progesterone Receptor-B (PR-B) in the endometrial luminal epithelial cells is the key mechanism that allows expression of estrogen receptor alpha and oxytocin receptor and development of the luteolytic mechanism in ruminants. However, the underlying mechanisms of  PR-B loss in the endometrial luminal epithelial cells during luteolysis remain unknown in ruminant reproduction. The objective is to identify and establish the epigenetic mechanisms that regulate the temporal and spatial expression of PR-B in the endometrial luminal epithelial cells during the estrous cycle in ruminants. The central hypothesis is that loss of PR-B expression in the endometrial luminal epithelial cells during luteolysis is regulated by DNA methylation and histone modification mechanisms in ruminants. Results indicated that intrauterine administration of DNA methylation inhibitor or H3K27 methylation inhibitor via osmotic mini pump from days 9/10 to 16 of the estrous cycle maintained the CL weight, volume, and progesterone secretion in 80% of the ewes. Immunohistochemistry results indicated that  DNA methylation and H3K27 methylation inhibition maintained the expression of PR-B protein in the endometrial luminal epithelial cells. Our ongoing research aims to identify the genes/proteins involved in the epigenetic regulation of PR-B using omics approaches. The project is funded by USDA-NIFA 2019-67015-29562.