Neonatal Exposure to Estrogen and Estrogen Receptor Agonists and Antagonists: Effects on the Adult Endometrial Proteome and Morphoregulatory Gene Expression in the Neonatal Uterus

Abstract

Development of the porcine uterus begins prenatally but is completed postnatally. In mammals, the uterus provides an embryotrophic environment for conceptus development and integrates maternal and conceptus signals needed for maintenance of pregnancy. The first two weeks of postnatal life are an important period for developmental programming of the endometrium. Disruption of this program by exposure of neonates to estradiol valerate (EV; 50ug/kg BW/day) for two weeks from birth affects adult uterine morphology, endometrial function and, ultimately, decreases embryo survival. Several morphoregulatory genes including Wnt4, Wnt5a, Wnt7a, Hoxa10 and Hoxa11 have been implicated in the development of the porcine female reproductive tract. Studies were conducted to determine if Indian Hedgehog (Ihh), Muscle Segment Homeobox 1 and 2 (Msx1, Msx2) were present in the developing porcine endometrium as well as if the expression patterns were altered by exposure to hormones. The adult endometrial proteome from day 12 pregnant pigs was also studied to determine effects of neonatal estrogen exposure.