Cell death in the sexually dimorphic dorsal preoptic area/anterior hypothalamus of perinatal male and female ferrets.

Abstract

A sexually dimorphic male nucleus (MN) is present in Nissl-stained sections through the dorsal (d) preoptic area/anterior hypothalamus (POA/AH) of male ferrets. The MN-POA/AH is composed of a cluster of large cells which is organized in males by the action of estradiol, formed via the neural aromatization of circulating testosterone (T), during the last quarter of a 41-day gestation. Several recent studies using rodent species have raised the possibility that the hormone-induced masculinization of POA/AH morphology is mediated at least in part by a perinatal modulation of cell death. We asked whether a perinatal reduction in cell death contributes to the differentiation of the MN-POA/AH in the male ferret, which is a carnivore species. The appearance of internucleosomal DNA fragmentation, detected by in situ end labeling (ISEL) using the ApopTag kit (Oncor Corp.) and of pyknotic cell nuclei in Nissl-stained sections were used to estimate the occurrence of cell death. Male and female ferret kits were killed at four different ages spanning the perinatal period during which the MN-POA/AH is organized and assumes an adult phenotype. A peak density of dying cells was present in both sexes at postnatal day (P) 2, which is nearly 1 week after the age, embryonic day (E) 37, when the MN-POA/AH is first visible in male ferrets using Nissl stains. The density of cells in the sexually dimorphic dPOA/AH which were either ISEL-positive or pyknotic was similar in males and females on E34, as well as on P2, 10, and 20. In the nondimorphic ventral POA/AH, the highest density of dying cells was present in both sexes at E34, and there were significantly more ISEL-positive cells present in males than females at this particular age. In contrast to previous studies using rodents, our results suggest that in fetal male ferrets a modulation of the incidence of cell death contributes little to estradiol's organizational action in the dPOA/AH.