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BOR - Papers in Press, published online ahead of print December 11, 2002.
Biol Reprod 2002, 10.1095/biolreprod.102.012708
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Submitted October 24, 2002
Returned for revision November 18, 2002
Accepted December 2, 2002

Immunology


Pregnancy and Interferon Tau Regulate Major Histocompatibility Complex Class I and Beta-2-Microglobulin Expression in the Ovine Uterus

Youngsok Choi , Greg A. Johnson , Thomas E. Spencer , Fuller W. Bazer *

* To whom correspondence should be addressed. E-mail: fbazer{at}cvm.tamu.edu.

Abstract

Major histocompatibility complex (MHC) class I molecules, consisting of an alpha ({alpha}) chain and beta-2- microglobulin ({beta}2MG), play an important role in immune rejection responses by discriminating self and non- self and are increased by Type I interferons during antiviral responses. Interferon tau (IFN{tau}), the pregnancy recognition signal in ruminants, is a Type I IFN produced by the ovine conceptus between Days 11 and 21 of gestation. In Study One, expression of MHC class I & [alpha] chain and {beta}2MG mRNA and protein was detected primarily in endometrial luminal epithelium (LE) and glandular epithelium (GE) on Days 10 and 12 of the estrous cycle and pregnancy. On Days 14 to 20 of pregnancy, MHC Class I and {beta}2MG expression increased only in endometrial stroma and GE and concurrently was absent in LE and superficial ductal GE (sGE). Although neither MHC Class I nor {beta}2MG proteins were detected in Day 20 trophectoderm, {beta} 2MG mRNA was detected in conceptus trophectoderm. In Study Two, cyclic ewes were ovariectomized on Day 5, treated daily with progesterone to Day 16, received intrauterine infusions between Days 11-16 of either control serum proteins or recombinant ovine IFN{tau}, and were hysterectomized on Day 17. IFN{tau} increased MHC class I and {beta}2MG expression only in endometrial stroma and GE. During pregnancy, MHC class I and {beta} 2MG gene expression is inhibited in endometrial LE and sGE, but is paradoxically stimulated by IFN{tau} in the stroma and GE. The silencing of MHC Class I {alpha} chain and {beta}2MG genes in the endometrial LE and sGE during pregnancy recognition and establishment may be a critical mechanism preventing immune rejection of the conceptus allograft.



Key words: Female Reproductive Tract • Immunology • Pregnancy • Trophoblast • Uterus


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