Influence of the antiandrogen flutamide on the androgen receptor gene expression in the placenta and umbilical cord during pregnancy in the pig

The aim of this study was to determine the immunolocalization and expression of the androgen receptor (AR) in the pig placenta and umbilical cord during pregnancy following exposure to flutamide, a non-steroidal antiandrogen, at its various stages. Pregnant pigs were injected with flutamide at a daily dose of 50 mg/kg body weight at different stages of pregnancy: from day 83-89 (n = 2); from day 101-107 (n = 2). They were sacrificed and tissues collected one day after the last injection. Control animals, two for each experimental point, were injected only with the vehicle (corn oil). Collected tissue samples were fixed for immunohistochemistry or frozen for protein isolation. AR protein was detected in the nucleus of trophoblast cells forming the structure of ridges and in maternal endothelial cells, which are involved in the placental barrier formation. It was also localized in the nuclei of cells forming umbilical cord components: allantoic duct epithelium, amniotic epithelium, Wharton's jelly and the muscular layer of the umbilical cord vein and arteries. Relative optical density analysis showed increased expression in the material derived from animals treated with flutamide. The presence of AR in the placental barrier and in the umbilical cord components suggests a role of androgen in those temporary organs. Flutamide could impact on the levels of the AR protein in the reproductive tracts during pregnancy in sows.