Grant: Project Grant

Male and female brains can differ in morphology and function. Sex hormones play a key role in defining sexual characteristics of the brain, with a surge in testosterone from the testis responsible for driving masculinization of the male brain. Since testis are not yet functional during gestation, it was assumed that embryonic neural development was insensitive to sex cues. However, recent data from our lab suggests this assumption is not true. For example, we find high levels of estrogen receptors in the progenitors of the developing hypothalamus, a brain region critical for various social behaviors. In addition, we show exposure to estrogen early in embryonic development causes a change in the differentiation of vasopressin circuits, a network that is highly sex dimorphic. Combined, these data suggest that the embryonic brain is sensitive to sex hormones, and we propose that sex differentiation of the brain occurs earlier than recognized. Here, we test the hypothesis that an embryonic estrogen surge initiates vasopressin sexual differentiation via a neurogenic mechanism prior to birth. To test this hypothesis, we will first define the window of when vasopressin neurons are born in males and females, as well as the requirement of estrogen. Next, we will study if local synthesis of sex hormones contributes to sex differentiation of vasopressin development in the embryo. Finally, we will assay the impact of embryonic sexual differentiation on adult vasopressin circuits and behaviors. The goal of this project is to characterize vasopressin sexual dimorphism in the embryonic and understands its impact on behaviors later in life.