Partial Demasculinization and Feminization of Sex Behavior in Male Rats by in Utero and Lactational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin Is Not Associated with Alterations in Estrogen Receptor Binding or Volumes of Sexually Differentiated Brain

Abstract

In utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure partially demasculinizes and feminizes sexual behavior in adult male rats, presumably by causing incomplete sexual differentiation of the central nervous system (CNS). Our objective was to determine if TCDD exposure affects other aspects of sexual differentiation of the CNS. Because sex differences in the estrogen receptor system are thought to play a role in sexually dimorphic estrogen-mediated responses, and because estrogen is an important activator of both male and female sex behavior, the possible effect of TCDD exposure on estrogen binding in specific brain nuclei was examined. In addition, we investigated effects of in utero and lactational TCDD exposure on sex differences in the volumes of brain nuclei which are dependent on steroid hormone stimulation during the period of CNS sexual differentiation. Pregnant Holtzman rats were given TCDD (0.7 μg/kg, po) or vehicle (control) on gestation Day 15. Offspring were exposed to TCDD in utero and via lactation and then assessed in adulthood. Demasculinized sexual behavior was evidenced in the TCDD-exposed males by increased intromission latencies and a greater number of intromissions prior to ejaculation. These males were then castrated, primed with ovarian steroids, and tested for feminine sexual behavior. In utero and lactational TCDD exposure increased both the frequency and intensity of lordotic behavior, indicating that the males were partially feminized. To determine if TCDD exposure had a generalized effect on estrogen receptor concentrations the arcuate nucleus, cortical and medial amygdala and the bed nucleus of the stria terminalis, previously found to have equivalent numbers of estrogen receptors in males and females, were evaluated in littermates of the rats whose sexual behavior had been assessed. TCDD had no effect in either sex. To determine if TCDD exposure had an effect specific to sexual differentiation of the brain, estrogen receptor concentrations in the medial preoptic nucleus (MPO), ventrolateral aspect of the ventromedial nucleus, and periventricular preoptic area were assessed. As expected, females had higher estrogen receptor concentrations in these nuclei than did males, but TCDD exposure did not affect estrogen receptor concentrations in any of these sexually dimorphic brain nuclei. The volumes of sexually dimorphic brain nuclei were examined in additional littermates. In control rats, the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) is larger in males than in females whereas the MPO is larger in females than in males. TCDD exposure had no effect on the volume of either the SDN-POA or MPO in either males or females. Our results indicate that in utero and lactational TCDD exposure causes a partial demasculinization and feminization of sex behavior that is not associated with an apparent effect on the sexual differentiation of the estrogen receptor system or the volume of sexually dimorphic brain nuclei.