The sexually dimorphic nucleus (SDN) in the preoptic area (POA) of the hypothalamus plays an important role in the development of sexual preference and behaviour in many species. It is well established that coital behaviour and gonatdotrophin secretion in sheep are masculinised by prenatal testosterone exposure. In other species, oestrogen derived by aromatization of testosterone, also plays a role in developmental organization of the male brain. Studies in rodents have shown that the SDN is susceptible to effects of exposure to endocrine disrupting chemicals (EDCs) which can alter the size of the SDN resulting in altered sexual behaviour. The present study examined whether developmental exposure to EDCs, by maternal exposure to chemicals in sewage sludge, altered oestrogen receptor alpha (ERα) expression in the SDN in adult sheep. Hypothalami were collected from 18 month old male and female sheep from ewes pastured on fields fertilised with inorganic fertiliser (control) or sewage sludge (SS, n=12 per group) throughout pregnancy. Immunohistochemistry for ERα was performed on 30µm sections (3 per animal) of the POA containing the SDN. The number of ERα-positive cells in the SDN was quantified using ImageJ (NIH). Mean data was analysed using 2-way ANOVA. The mean number of ERα positive cells within the SDN was significantly greater in control males compared to control females (p=0.0433). Females exposed to SS in-utero had significantly fewer ERα positive cells compared with controls (p≺0.05) whereas SS-exposed males had a trend for an increase in the number of ERα positive cells (p=0.1). Significant differences in ERα number between males and females was not found in the SS exposed groups. The current results suggest that developmental exposure to EDCs in-utero may alter the number of ERα cells expressed in the SDN in adulthood which could have consequences on sexual behaviour and mate preference in sheep.

 [Supported by the Wellcome Trust grant 080338]