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.

我们假设，从祖先开始，性别特异性免疫调节的进化是为了促进孕妇在存在侵入性胎盘和免疫挑战怀孕的情况下生存——我们将这一想法称为“妊娠补偿假说”（PCH）。此外，我们认为免疫功能的性别差异至少部分是由性染色体上基因含量和剂量的进化介导的，并受到生殖激素的调节。最后，我们提出，工业化环境中生殖生态的变化加剧了这些进化的性别差异，导致女性患自身免疫性疾病的风险增加，并抵消了可以通过加强免疫监视来对抗的癌症等疾病的减少。 PCH 产生了一系列可以通过经验检验的期望，这可能有助于确定现代人类疾病中性别差异的潜在机制。