Progesterone modulation of osteopontin gene expression in the ovine uterus

Osteopontin (OPN) is an acidic phosphorylated glycoprotein component of the extracellular matrix that binds to integrins at the cell surface to promot e cell-cell attachment and cell spreading. This matrix constituent is a lig and 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 O PN 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,) cathete rs on Day 5 and treated daily with steroids (i.m,) and protein (i.u.) as fo llows: 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, Day s 11-24) and CX proteins; 3) P and recombinant ovine IFN tau (rolFN tau, Da ys 11-24); or 4) P and ZK and rolFN tau. All ewes were hysterectomized on D ay 25. Progesterone induced the expression of endometrial OPN mRNA in the C E 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 rolFN tau did not affect OPN gene express ion or secretion in any of the steroid treatments. Interestingly, OPN mRNA- positive CE cells lacked detectable PR expression, although PR were detecte d in the stroma. Results indicate that progesterone regulates OPN expressio n in CE through a complex mechanism that includes PR down-regulation, and w e suggest the possible involvement of a progesterone-induced stromal cell-d erived growth factor(s) that acts as a progestamedin.