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Biology of Reproduction 62, 1315-1321 (2000)
© 2000 Society for the Study of Reproduction, Inc.

Articles

Progesterone Modulation of Osteopontin Gene Expression in the Ovine Uterus1

Greg A. Johnsona,b, Thomas E. Spencera,b, Robert C. Burghardta,c, Kristin M. Taylora,b, C. Allison Graya,b, and Fuller W. Bazer2,,a,b

a Center for Animal Biotechnology and Genomics, b Institute of Biosciences and Technology, Texas A&M University System Health Center; Departments of Animal Science and c Veterinary Anatomy & Public Health, Texas A&M University, College Station, Texas 77843-2471

Osteopontin (OPN) is an acidic phosphorylated glycoprotein component of the extracellular matrix that binds to integrins at the cell surface to promote cell-cell attachment and cell spreading. This matrix constituent is a ligand that could potentially bind integrins on trophectoderm and endometrium to facilitate superficial implantation and placentation. OPN mRNA increases in the endometrial glandular epithelium (GE) of early-pregnant ewes, and OPN protein is secreted into the uterine lumen. Therefore, progesterone and/or interferon-tau (IFN{tau}) may regulate OPN expression in the uterine GE. Cyclic ewes were ovariectomized and fitted with intrauterine (i.u.) catheters on Day 5 and treated daily with steroids (i.m.) and protein (i.u.) as follows: 1) progesterone (P, Days 5–24) and control serum proteins (CX, Days 11–24); 2) P and ZK 136.317 (ZK; progesterone receptor [PR] antagonist, Days 11–24) and CX proteins; 3) P and recombinant ovine IFN{tau} (roIFN{tau}, Days 11–24); or 4) P and ZK and roIFN{tau}. All ewes were hysterectomized on Day 25. Progesterone induced the expression of endometrial OPN mRNA in the GE and increased secretion of a 45-kDa OPN protein from endometrial explants maintained in culture for 24 h. Administration of ZK ablated progesterone effects. Intrauterine infusion of roIFN{tau} did not affect OPN gene expression or secretion in any of the steroid treatments. Interestingly, OPN mRNA-positive GE cells lacked detectable PR expression, although PR were detected in the stroma. Results indicate that progesterone regulates OPN expression in GE through a complex mechanism that includes PR down-regulation, and we suggest the possible involvement of a progesterone-induced stromal cell-derived growth factor(s) that acts as a progestamedin.

First decision: 18 November 1999.

1 Research supported by USDA-NRICGP 95–37203-2185 to F.W.B. and R.C.B., and by NIH 1-F32-HD08501-01A1 to G.A.J.

2 Correspondence: Fuller W. Bazer, Department of Animal Science and Center for Animal Biotechnology and Genomics, 442D Kleberg Center, Texas A&M University, College Station, TX 77843-2471. FAX: 409 862 2662; fbazer{at}cvm.tamu.edu




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