PLATFORM SESSION 18: IMPACT OF IMMUNITY, AGING, AND NUTRITION ON REPRODUCTION
Chair: Bacon, Sarah1, 1
Co-chair: Cannon, Matthew1, 1
2:00 PM-4:00 PM
(424) EXPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I AND 2-MICROGLOBULIN GENES IN THE OVINE UTERUS.
Choi, Youngsok1, Burghardt, Robert1, Bazer, Fuller1, Spencer, Thomas1, 1 Center for Animal Biotechnology and Genomics, College Station, TX
ABSTRACT- Major histocompatibility complex (MHC) class I molecules include chain and -2-microglobulin (2MG) which express in all nucleated cells and are involved in immune rejection responses by differentiating self from non-self. Interferon tau (IFN), a novel Type I IFN produced by the trophectoderm from Days 11 to 21-25 in sheep, is the pregnancy recognition signal that induces or increases expression of IFN-stimulated genes, including MHC class I and 2MG. Studies were conducted to determine effects of the estrous cycle, pregnancy and IFN on expression of MHC class I chain and 2MG in the ovine uterus. In Study One, ewes were hysterectomized (n=5/day) on Days 10, 12, 14 or 16 of the estrous cycle or Days 10, 12, 14, 16, 18 or 20 of pregnancy. In Study Two, cyclic ewes (n=5/treatment) were ovariectomized and fitted with intrauterine catheters on Day 5, treated daily with 50 mg progesterone from Days 5 to 16, infused daily with either control protein or recombinant ovine IFN (1x108 AVU/day) from Days 11 to 16, and were hysterectomized on Day 17. In cyclic ewes, low expression of MHC class I and 2MG mRNAs was detected in luminal epithelium (LE), glandular epithelium (GE), stroma and myometrium of the ovine uterus. In pregnant ewes, MHC class I and 2MG mRNAs were not detected in the endometrial LE or conceptus, but were increased in stroma and GE on Days 14, 16, 18 and 20. Steady-state levels of endometrial MHC class I and 2MG mRNAs did not change in cyclic ewes, but increased in pregnant ewes from Days 12 to 14 and remained high thereafter (P<0.0001, day x status). In cyclic ewes treated with progesterone, intrauterine infusion of IFN increase (P<0.0001) steady-state levels of endometrial MHC class I and 2MG mRNAs 3.8-fold and 2.7-fold, respectively, only in the stroma and GE. These novel results indicate that: (1) MHC class I and 2MG are not expressed in endometrial LE or conceptus, but are increased in stroma and GE by the conceptus during the period of pregnancy recognition and implantation; and (2) IFN increases expression of MHC class I chain and 2MG genes only in the stroma and GE. The mechanism for silencing transcription of MHC class I and 2MG genes in endometrial LE remains to be determined, but is likely to be a critical mechanism to avoid rejection of the conceptus allograft during pregnancy. Supported by NIH HD32534.
KEY WORDS: uterus, beta-2 microglobulin, interferon tau, mhc class I