Uterine MHC class I molecules and beta 2-microglobulin are regulated by progesterone and conceptus interferons during pig pregnancy.
MHC class I molecules and beta(2)-microglobulin (beta(2)m) are membrane glycoproteins that present peptide Ags to TCRs, and bind to inhibitory and activating receptors on NK cells and other leukocytes. They are involved in the discrimination of self from non-self. Modification of these molecules in the placenta benefits pregnancy, but little is known about their genes in the uterus. We examined the classical class I swine leukocyte Ags (SLA) genes SLA-1, SLA-2, and SLA-3, the nonclassical SLA-6, SLA-7, and SLA-8 genes, and the beta(2)m gene in pig uterus during pregnancy. Uterine SLA and beta(2)m increased in luminal epithelium between days 5 and 9, then decreased between days 15 and 20. By day 15 of pregnancy, SLA and beta(2)m increased in stroma and remained detectable through day 40. To determine effects of estrogens, which are secreted by conceptuses to prevent corpus luteum regression, nonpregnant pigs were treated with estradiol benzoate, which did not affect the SLA or beta(2)m genes. In contrast, progesterone, which is secreted by corpora lutea, increased SLA and beta(2)m in luminal epithelium, whereas a progesterone receptor antagonist (ZK137,316) ablated this up-regulation. To determine effects of conceptus secretory proteins (CSP) containing IFN-delta and IFN-gamma, nonpregnant pigs were implanted with mini-osmotic pumps that delivered CSP to uterine horns. CSP increased SLA and beta(2)m in stroma. Cell-type specific regulation of SLA and beta(2)m genes by progesterone and IFNs suggests that placental secretions control expression of immune regulatory molecules on uterine cells to provide an immunologically favorable environment for survival of the fetal-placental semiallograft.
Joyce
Margaret M
MM
Center for Animal Biotechnology and Genomics, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4458, USA.
Burghardt
James R
JR
Burghardt
Robert C
RC
Hooper
R Neil
RN
Bazer
Fuller W
FW
Johnson
Greg A
GA
D000818:Animals; D010064:Embryo Implantation / Q000276:immunology*; D004717:Endometrium / Q000276:immunology / Q000378:metabolism; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II; D007370:Interferon Type I / Q000378:metabolism / Q000502:physiology; D007371:Interferon-gamma / Q000378:metabolism / Q000502:physiology; D007372:Interferons / Q000378:metabolism* / Q000502:physiology; D008431:Maternal-Fetal Exchange / Q000276:immunology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000096:biosynthesis* / Q000378:metabolism; D011374:Progesterone / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D013552:Swine / Q000196:embryology / Q000276:immunology*; D014599:Uterus / Q000276:immunology* / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000096:biosynthesis / Q000378:metabolism*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007370:Interferon Type I; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; C037655:interferon, delta; C438668:swine leukocyte antigen; D011374:Progesterone; D007371:Interferon-gamma; D007372:Interferons