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

Research output: Contribution to journalReview article

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)478-488
Number of pages11
JournalTrends in Genetics
Volume35
Issue number7
DOIs
StatePublished - Jul 2019

Keywords

  • X inactivation
  • autoimmunity
  • cancer
  • dosage compensation
  • placentation
  • pregnancy compensation hypothesis
  • sex differences

ASJC Scopus subject areas

  • Genetics

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