The Pregnancy Pickle: Evolved Immune Compensation Due to Pregnancy Underlies Sex Differences in Human Diseases

Bibliographic Collection: 
APE
Publication Type: Journal Article
Authors: Natri, Heini; Garcia, Angela R.; Buetow, Kenneth H.; Trumble, Benjamin C.; Wilson, Melissa A.
Year of Publication: 2019
Journal: Trends in Genetics
Volume: 35
Issue: 7
Pagination: 478 - 488
Date Published: 2019/07/01
Publication Language: eng
ISBN Number: 0168-9525
Abstract:

We hypothesize that, ancestrally, sex-specific immune modulation evolved to facilitate survival of the pregnant person in the presence of an invasive placenta and an immunologically challenging pregnancy ? an idea we term the 'pregnancy compensation hypothesis' (PCH). Further, we propose that sex differences in immune function are mediated, at least in part, by the evolution of gene content and dosage on the sex chromosomes, and are regulated by reproductive hormones. Finally, we propose that changes in reproductive ecology in industrialized environments exacerbate these evolved sex differences, resulting in the increasing risk of autoimmune disease observed in females, and a counteracting reduction in diseases such as cancer that can be combated by heightened immune surveillance. The PCH generates a series of expectations that can be tested empirically and that may help to identify the mechanisms underlying sex differences in modern human diseases.We hypothesize that, ancestrally, sex-specific immune modulation evolved to facilitate survival of the pregnant person in the presence of an invasive placenta and an immunologically challenging pregnancy ? an idea we term the 'pregnancy compensation hypothesis' (PCH). Further, we propose that sex differences in immune function are mediated, at least in part, by the evolution of gene content and dosage on the sex chromosomes, and are regulated by reproductive hormones. Finally, we propose that changes in reproductive ecology in industrialized environments exacerbate these evolved sex differences, resulting in the increasing risk of autoimmune disease observed in females, and a counteracting reduction in diseases such as cancer that can be combated by heightened immune surveillance. The PCH generates a series of expectations that can be tested empirically and that may help to identify the mechanisms underlying sex differences in modern human diseases.

Notes:

doi: 10.1016/j.tig.2019.04.008

DOI: https://doi.org/10.1016/j.tig.2019.04.008
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