Immunohistochemical studies on the proliferative marker Ki-67 and estrogen receptor alpha (ERα) in the uterus of neonatal and immature pigs following exposure to flutamide.

The development of uterine glands is characterized by the proliferation of epithelial cells and by estrogen receptor alpha (ERα) expression in the nascent glandular epithelium. It is known that androgen receptors are present in the porcine uterus during prenatal development and the neonatal window, when adenogenesis occurs. Therefore, the objective of the study was to determine whether the effects of maternal or neonatal administration of the anti-androgen, flutamide, could entail changes in the presence of ERα and proliferation of uterine cells in neonatal and three-month-old pigs. Following prenatal flutamide exposure, morphological differences and the acceleration of uterus differentiation marked by ERα expression in epithelial crypts were observed in the neonatal piglets. In the three-month-old pig uterus, the proliferation of stromal cells was observed only after prenatal exposure to flutamide, whereas ERα staining was weaker. The neonatal administration of flutamide caused a significant decrease in the proliferation of the surface epithelium and diminished intensity of ERα staining in the stromal cells of the uterus of three-month-old pigs, which paralleled decreased estrogen levels in these animals. Overall, prenatal flutamide exposure promoted growth and development of the neonatal porcine uterus. Moreover, in three-month-old pigs, flutamide application during the neonatal period decreased surface epithelium proliferation and stromal ERα expression, which confirmed the importance of epithelial-stromal interactions in the adenogenesis.