Effect of Steroids on HOXA10 mRNA and Protein Expression and Prostaglandin Production in the Porcine Endometrium

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The homeobox A (HOXA) family of genes is responsible for segmental development of the female reproductive tract during embryogenesis. However, HOXA10 has been shown to be essential not only for uterus development, but also for implantation. Persistent expression and steroid-dependent regulation of this gene has been demonstrated in adult human, primate, murine and canine uteri. Moreover, HOXA10-dependent expression of prostaglandin H synthase-2 (PGHS-2), a key enzyme in prostaglandin production, has been previously detected. The role of the HOXA10 gene in the porcine uterus is not well established. Therefore, the present studies were undertaken to 1) examine the effect of E(2) and P(4) on HOXA10 mRNA and protein content in the endometrium collected on day 9 of the estrous cycle and 2) determine the PGHS-2 protein expression and PGE(2) and PGF(2α) secretion from endometrial tissue in response to steroid treatment. Endometrial explants collected from mature gilts on day 9 of the estrous cycle were incubated with E(2) (1-100 nM), P(4) (10-1000 nM) or E(2) (10 nM) and P(4) (100 nM) for 24 h. E(2) alone or E(2) in the presence of P(4) increased HOXA10 mRNA expression in the endometrium (P<0.05). The HOXA10 protein level was upregulated in response to E(2), P(4) and both steroids administered simultaneously (P<0.05). Moreover, E(2) and P(4) stimulated PGHS-2 protein expression in cultured endometrial explants. PGE(2), but not PGF(2α), secretion increased in the presence of E(2) (P<0.05). However, the release of both prostaglandins was decreased after treatment of endometrial explants with the highest dose of P(4) (P<0.01). These results demonstrate that E(2) and P(4) are important regulators of HOXA10 gene expression in the adult porcine endometrium during the mid-luteal phase of the estrous cycle. Additionally, the similar profiles of endometrial HOXA10 and PGHS-2 expression in the presence of E(2) and P(4) indicate that both genes are simultaneously regulated by steroids in the porcine uterus.