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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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biolreprod.102.012708v1
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BIOLOGY OF REPRODUCTION 68, 1703–1710 (2003)
DOI: 10.1095/biolreprod.102.012708
© 2003 by the Society for the Study of Reproduction, Inc.


Immunology

Pregnancy and Interferon Tau Regulate Major Histocompatibility Complex Class I and ß2-Microglobulin Expression in the Ovine Uterus1

Youngsok Choi3, Greg A. Johnson4, Thomas E. Spencer3, and Fuller W. Bazer2,3

Center for Animal Biotechnology and Genomics, Department of Animal Science3 Department of Veterinary Anatomy and Public Health,4 Texas A&M University, College Station, Texas 77843

Major histocompatibility complex (MHC) class I molecules, consisting of an {alpha} chain and ß2-microglobulin (ß2MG), play an important role in immune rejection responses by discriminating self and nonself and are increased by type I interferons during antiviral responses. Interferon tau (IFN{tau}), the pregnancy-recognition signal in ruminants, is a type I interferon produced by the ovine conceptus between Days 11 and 21 of gestation. In study 1, expression of MHC class I {alpha} chain and ß2MG 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 14–20 of pregnancy, MHC class I and ß2MG 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 ß2MG proteins were detected in Day 20 trophectoderm, ß2MG mRNA was detected in conceptus trophectoderm. In study 2, cyclic ewes were ovariectomized on Day 5, treated daily with progesterone to Day 16, received intrauterine infusions between Days 11 and 16 of either control serum proteins or recombinant ovine IFN{tau}, and were hysterectomized on Day 17. The IFN{tau} increased MHC class I and ß2MG expression only in endometrial stroma and GE. During pregnancy, MHC class I and ß2MG gene expression is inhibited in endometrial LE and sGE but, paradoxically, is stimulated by IFN{tau} in the stroma and GE. The silencing of MHC class I {alpha} chain and ß2MG genes in the endometrial LE and sGE during pregnancy recognition and establishment may be a critical mechanism preventing immune rejection of the conceptus allograft.

1 Supported by NIH grant HD32534 to F.W.B. and T.E.S. and NIH grant 5 P30 ES09106.

2 Correspondence: Fuller W. Bazer, Center for Animal Biotechnology and Genomics, 442D Kleberg Center, 2471 TAMU, Texas A&M University, College Station, TX 77843-2471. FAX: 979 845 9938; fbazer{at}cvm.tamu.edu




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