TY - JOUR T1 - Mast Cells in the Developing Brain Determine Adult Sexual Behavior JF - bioRxiv DO - 10.1101/205559 SP - 205559 AU - Kathryn M. Lenz AU - Lindsay A. Pickett AU - Christopher L. Wright AU - Katherine T. Davis AU - Anabel Galan AU - Margaret M. McCarthy Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/10/19/205559.abstract N2 - Sex differences in brain and behavior are programmed during development by gonadal hormones. We found that the immune system-derived mast cell is a primary target for the masculinizing hormone, estradiol. Male rats had more mast cells in the preoptic area (POA), a brain region essential for male copulatory behavior, during the critical period for sexual differentiation. Activating mast cells in females masculinized POA neuronal and microglial morphology and adult sex behavior, and inhibiting mast cells in males blunted masculinization. Estradiol increased mast cell number and caused mast cells to release histamine, which stimulated microglia to release prostaglandins and thereby induced male-typical synaptic patterning. Inducing an allergic reaction in pregnant dams increased mast cell number in the brains of female fetuses and masculinized neuronal and microglia morphology and adult copulatory behavior. These findings identify a novel non-neuronal origin of brain sex differences and non-steroidal source of variability in brain feminization. ER -