@article{7b5060552a5a451d95a03eaef22b13f1,
title = "The Pregnancy Pickle: Evolved Immune Compensation Due to Pregnancy Underlies Sex Differences in Human Diseases",
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.",
keywords = "X inactivation, autoimmunity, cancer, dosage compensation, placentation, pregnancy compensation hypothesis, sex differences",
author = "Heini Natri and Garcia, {Angela R.} and Buetow, {Kenneth H.} and Trumble, {Benjamin C.} and Wilson, {Melissa A.}",
note = "Funding Information: This study was supported by Arizona State University (ASU) Center for Evolution and Medicine postdoctoral fellowships to H.N. and A.R.G., a Marcia and Frank Carlucci Charitable Foundation postdoctoral award from the Prevent Cancer Foundation to H.N., startup funds from the School of Life Sciences and the Biodesign Institute at ASU to M.A.W., and partial support from National Institutes of Health (NIH)/ National Institute on Aging (NIA) grant RF1AG054442-01 to B.C.T. This study was supported by the National Institute of General Medical Sciences of the NIH under award R35GM124827 to M.A.W. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: This study was supported by Arizona State University (ASU) Center for Evolution and Medicine postdoctoral fellowships to H.N. and A.R.G. a Marcia and Frank Carlucci Charitable Foundation postdoctoral award from the Prevent Cancer Foundation to H.N. startup funds from the School of Life Sciences and the Biodesign Institute at ASU to M.A.W. and partial support from National Institutes of Health (NIH)/National Institute on Aging (NIA) grant RF1AG054442-01 to B.C.T. This study was supported by the National Institute of General Medical Sciences of the NIH under award R35GM124827 to M.A.W. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",
year = "2019",
month = jul,
doi = "10.1016/j.tig.2019.04.008",
language = "English (US)",
volume = "35",
pages = "478--488",
journal = "Trends in Genetics",
issn = "0168-9525",
publisher = "Elsevier Limited",
number = "7",
}