Expression and regulation of select interferon stimulated genes in porcine endometrium during pregnancy
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Coordinated signals between the maternal endometrium and conceptus during the peri-implantation period are essential for the establishment and maintenance of pregnancy. In pigs, this involves estrogen secretion from conceptuses as the signal for maternal recognition of pregnancy. Pig conceptuses also secrete interferons (IFN) delta (IFND) and IFN gamma (IFNG). The uterine effects of pig IFNs are not known, although ruminant conceptuses secrete IFN tau (IFNT) for pregnancy recognition, and this increases the expression of IFN-stimulated genes (ISGs) in the endometrium. Therefore, studies were conducted to identify and characterize ISGs in the pig endometrium during pregnancy and to evaluate their regulation by estrogen and conceptus secretory proteins (CSPs) that contain IFNs. In the first study, four classical ISGs, including interferon regulatory factor 1 (IRF1) and signal transducer and activator of transcription 2 (STAT2), were detected in the pig endometrium and increased after Day 12 of pregnancy, specifically in stroma. IRF2, a transcriptional repressor of ISGs, increased in luminal epithelium (LE) by Day 12 of pregnancy. The increase of IRF2 was due to estrogen while the stromal increase of IRF1 was due to IFN-containing CSP infusion. In the second study, the ISG STAT1 increased in LE after Day 12 of pregnancy and estrogen resulted in a similar increase. After Day 15 of pregnancy, STAT1 increased in stroma. Infusion of IFN-containing CSPs resulted in a similar stromal increase. In the third study, the ISGs swine leukocyte antigen (SLA) class I and beta-2microglobulin (B2M) increased in LE between Days 5 and 9 of the estrous cycle and pregnancy and decreased between Days 15 and 20 of pregnancy. By Day 15 of pregnancy, SLAs and B2M increased in stroma where they remained through Day 40. Progesterone increased SLA and B2M in LE, and a progesterone receptor antagonist ablated the upregulation while infusion of IFN-containing CSP increased SLA and B2M in stroma. Collectively, these studies identify ISGs expressed in the pig endometrium during pregnancy. These genes may be involved in protecting the fetal semiallograft from immune rejection, limiting conceptus invasion through the uterine wall, and/or establishing a vascular supply to the conceptus. The interactions of estrogen, progesterone and IFNs to regulate cell-type specific expression of ISGs highlight the complex interplay between endometrium and conceptus for pregnancy recognition and implantation.
Joyce, Margaret Mary (2008). Expression and regulation of select interferon stimulated genes in porcine endometrium during pregnancy. Doctoral dissertation, Texas A&M University. Available electronically from