Hypothalamic vasopressin sex differentiation is established during embryonic neurogenesis

Arginine vasopressin (AVP) is a conserved sexually dimorphic system regulating behaviors and physiologies. Decades of research concludes that AVP sex differentiation in mice occurs around birth when a gonadal surge of testosterone is converted to estrogen in male sexual dimorphic brain regions. We discovered that AVP neurons in the murine hypothalamus are sexually dimorphic much earlier than this surge, with male mice displaying more AVP neurons than females during neurogenesis at E11. In utero exposure to a pan-ER antagonist blocked AVP masculinization in males, whereas embryonic exogenous 17β-estradiol or xenoestrogen bisphenol A (BPA) masculinized female AVP neurons, causing permanent masculinization effects on adult female AVP cell numbers, projections and intrinsic neuronal properties. Our data reveal that sexual dimorphism of hypothalamic AVP neurons is present from the earliest stages of their differentiation and challenges current dogma that masculinization of the male brain occurs around birth. One-Sentence Summary Sexual dimorphism of hypothalamic vasopressin is established during neurogenesis and exposure to the xenoestrogen bisphenol A during pregnancy induces masculinization of female brains