Perinatal androgen exposure impacts mast cell development and mediator storage

Abstract

Abstract Mast cell (MC)-associated diseases often exhibit a female sex bias in both prepubertal children and adults. We have shown that female MCs store and release greater amounts of histamine which correlates with heightened anaphylaxis in both prepubertal and adult mice. Further, perinatal androgen exposure, a major organizing event in sex biology, reduced MC histamine storage and release, and the severity of anaphylaxis in prepubertal and adult female mice, thus demonstrating that perinatal androgens are critical early life drivers of MC sex differences, but the mechanisms remain poorly understood. The objective of this study was to determine how perinatal androgens impact MC development. RNA sequencing analysis of BMMCs derived from adult female and male mice that were previously exposed to perinatal androgens revealed significant down-regulation of a number of genes related to granule biogenesis and mediator storage of which included lactotransferrin (by −2.6 fold), proteoglycan 2 (by −3.9 fold), lipocalin 2 (by −1.4-fold), elastase (by −2.5 fold) and myeloperoxidase (by 1.4 fold). Current studies aim to confirm RNA seq data with qPCR and protein expression analysis and to define the critical period of androgen programming on MC development and function. Understanding the mechanisms by which early life androgens drive sex differences in MCs will be critical in understanding the origins of sex differences in MC and its role in health and disease.