Role of the estrogen receptor system in neonatal porcine uterine development

Studies described herein were designed to test the hypotheses that: (1) the porcine uterus acquires the ability to respond to estrogen progressively after birth (postnatal day = PND 0); (2) estrogen receptor-α (ER) expression and activation are required for normal development of the neonatal porcine uterine wall; (3) targeted, aberrant hyperactivation of the neonatal uterine ER system would affect uterine morphology and endometrial functionality later in life in a manner that could be related to endometrial ER architecture (the relative presence, distribution and relationships between ER+ and ER− cells in endometrial stroma, luminal epithelium (LE) and glandular epithelium (GE)) characteristic of the neonatal period when estrogen exposure occurred; and (4) long-term effects of transient neonatal exposure to estradiol valerate (EV) from PND 0 through PND 13, an established critical period for porcine uterine development, would affect the capacity of the adult porcine uterus to accommodate to conditions of pregnancy characteristic of the periattachment period.; Collectively, results of the first two studies establish that the porcine uterus acquires the ability to respond directly to estrogens postnatally, that acquisition of this ER+ phenotype is programmed developmentally, and that the activated ER system is required for the normal process of uterine maturation and endometrial gland development. Results of the last two studies indicate that estrogen-sensitive developmental events characteristic of the first few weeks of postnatal life are determinants of adult uterine morphology and functionality and, therefore, represent factors that affect the capacity of uterine tissues to accommodate pregnancy. Results also show that the long-term consequences of transient neonatal estrogen exposure are negative for uterine function and capacity in the pig. Data establish that EV can be used as a tool with which to disrupt uterine development in the neonatal pig. The lesioned uterus produced by this treatment provides an experimental model system with which to identify estrogen-sensitive cellular and molecular determinants of uterine development and function. (Abstract shortened by UMI.)...