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Pig Conceptuses Secrete Estrogen and Interferons to Differentially Regulate Uterine STAT1 in a Temporal and Cell Type-Specific Manner

Center for Animal Biotechnology and Genomics and Department of Veterinary Integrative Bioscience (M.M.J., R.C.B., J.R.B., G.A.J.), Department of Large Animal Clinical Sciences (R.N.H.), College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas 77843; Department of Animal Science (R.D.G., J.W.R.), College of Agriculture, Food and Natural Resources, University of Missouri-Columbia, Columbia, Missouri 65211; and Department of Animal Science (M.D.A.), Oklahoma State University, Stillwater, Oklahoma 74078

Address all correspondence and requests for reprints to: Greg A. Johnson, Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas. E-mail: gjohnson{at}cvm.tamu.edu.

Conceptus trophectoderm and uterine luminal epithelial cells interact via endocrine, paracrine, and autocrine modulators to mediate pregnancy recognition and implantation. Pig conceptuses not only release estrogens for pregnancy recognition but also secrete interferons during implantation. Because interferon-stimulated genes are increased by interferons secreted for pregnancy recognition in ruminants, we asked whether the interferon-stimulated gene, STAT1, is up-regulated in pig endometrium by conceptus estrogens and/or interferons. STAT1 expression in response to day of pregnancy, estrogen injection, and intrauterine infusion of conceptus secretory proteins in pigs indicated 1) estrogen increases STAT1 in luminal epithelial cells, 2) conceptus secretory proteins that contain interferons increase STAT1 in stroma, 3) STAT1 increases in close proximity to the conceptus, and 4) early estrogen results in conceptus death and no STAT1 in stroma. The interactions of estrogen and interferons to regulate cell-type-specific expression of STAT1 highlight the complex interplay between endometrium and conceptus for pregnancy recognition and implantation.