Perinatal androgens organize sex differences in mast cells and attenuate anaphylaxis severity into adulthood
Emily Mackey, Kyan Thelen, Vedrana Bali, Mahsa Fardisi, Madalyn Trowbridge, Cynthia L. Jordan, Adam J. Moeser
Abstract
Significance Mast cell (MC)-associated disorders exhibit a sex bias, with females at increased risk. While attention has been directed to adult sex hormones as a mechanism for disease risk between the sexes, epidemiological evidence clearly shows that these same sex biases also exist in prepubertal children, thus challenging this concept. Here, we show that perinatal, but not adult gonadal, androgens play a protective role in MC-mediated anaphylaxis severity into adulthood. We propose that perinatal androgens mediate their protective effects via programming of bone marrow MC precursors to exhibit reduced granule histamine and release. These findings shift attention to perinatal life as a critical period for potential interventions to mitigate MC-associated disease risk across the lifespan in males and females.