Abstract. 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 E2 and P4 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 PGE2 and PGF2α 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 E2 (1-100 nM), P4 (10-1000 nM) or E2 (10 nM) and P4 (100 nM) for 24 h. E2 alone or E2 in the presence of P4 increased HOXA10 mRNA expression in the endometrium (P<0.05). The HOXA10 protein level was upregulated in response to E2, P4 and both steroids administered simultaneously (P<0.05). Moreover, E2 and P4 stimulated PGHS-2 protein expression in cultured endometrial explants. PGE2, but not PGF2α, secretion increased in the presence of E2 (P<0.05). However, the release of both prostaglandins was decreased after treatment of endometrial explants with the highest dose of P4 (P<0.01). These results demonstrate that E2 and P4 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 E2 and P4 indicate that both genes are simultaneously regulated by steroids in the porcine uterus. Key words: Endometrium, Estradiol, HOXA10, PGHS-2, Pig, Progesterone, Prostaglandins (J. Reprod. Dev. 56: [643][644][645][646][647][648] 2010) he uterine endometrium is one of the most dynamic tissues in the organism, undergoing morphological and physiological changes during each estrous cycle. Disorders in endometrial development may lead to lack of or improper implantation, pregnancy failure or infertility. Among the different hormones, estradiol (E2) and progesterone (P4) of ovarian origin are crucial regulators of endometrial receptivity and embryo-maternal cross-talk in many species [1][2][3][4]. It is obvious that the action of P4 in priming the uterus is absolutely essential to attain uterine receptivity for implantation, but the requirement of E2 of ovarian origin is speciesspecific [1]. However, the molecular mechanisms that direct the ordered proliferation, differentiation and cell death associated with the normal menstrual or estrous cycles are still not well characterized. Good candidates for regulation of gene expression in the endometrium are ho...