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The contributions of the conceptus (embryo and associated membranes) and of the maternal endocrine milieu to control of endometrial secretory leukocyte protease inhibitor (SLPI, also designated antileukoproteinase) expression during the periimplantation stages of embryo development were examined in the present study. Uterine endometrium from distinct sites was collected from pigs at Days 16-25 of pregnancy and analyzed for steady-state SLPI mRNA levels. Endometrium situated directly beneath conceptuses (mesometrial) had greater (p &lt; 0.05) SLPI mRNA levels than that obtained from antimesometrial and interimplantation sites and myometrium. This site-specific difference was most pronounced during late (Days 19-21) and post (Days 23-25)-implantation stages and was also observed, albeit to a lesser degree, for the mRNA encoding uteroferrin (Uf). Conditioned medium (CM; 50% v:v) from Day 21, but not Day 12, conceptuses increased (p &lt; 0.05) SLPI mRNA levels, while neither CM affected mRNA levels for Uf and several other genes expressed in endometrial explants. One inducing factor in Day 21 CM was characterized as a low-molecular-mass (&lt; 12 kDa), relatively heat-stable protein. Transforming growth factor (TGF alpha) increased (p &lt; 0.05), epidermal growth factor (EGF) tended to increase (p = 0.10), and insulin-like growth factor (IGF)-I and IGF-II had no effect (p &gt; 0.10) on, SLPI mRNA levels in Day 12 endometrial explants. Medium conditioned by the pig trophoblast cell line, Jag-1, but not by other mammalian cell lines, had SLPI inducer activity. The maternal endocrine contribution to SLPI gene expression was examined using freshly isolated and short-term-cultured Day 12 and Day 21 pregnant pig endometrium. Steady-state SLPI mRNA levels were increased (p &lt; 0.05) in Day 12, but not Day 21, tissues upon short-term culture in serum-free medium. This increase was time dependent, was similarly demonstrated for Uf mRNA, was not observed in corresponding lung and liver, and was inhibited by inclusion of serum from pigs of diverse endocrine status. In summary, two potential modulators of endometrial SLPI gene expression were identified: 1) a conceptus-derived low-molecular-mass protein, possibly TGF alpha, that mediates in part the up-regulation of SLPI gene expression in endometrium closely associated with implantation sites, and 2) an inhibitory component(s) present in maternal serum. Results suggest opposing actions of maternal and embryonic factors at the maternal-embryo interface and highlight involvement of the periimplantation embryo in directing the spatiotemporal expression of endometrial genes implicated in its development.

biology of reproduction

Control of Secretory Leukocyte Protease Inhibitor Gene Expression in the Porcine Periimplantation Endometrium: A Case of Maternal-Embryo Communication1