1Center for Evolution and Medicine, Arizona State University, 2School of Life Sciences, Arizona State University, 3School of Human Evolution and Social Change, Arizona State University
April 16, 2020 , Platinum Ballroom
Sex differences exist across a range of human diseases, that to date have been understudied and largely unexplained. For example, females in industrialized populations exhibit a higher prevalence of most autoimmune diseases than do males. By contrast, females have a lower risk of developing cancer, with nearly all cancers showing a higher incidence in males. Here we present the Pregnancy Compensation Hypothesis (PCH), which explains both the proximate and ultimate (evolutionary) mechanisms responsible for sexual dimorphism observed in human disease, as mediated by selection on the immune system due to pregnancy and placentation. We suggest that because evolution has shaped the human immune system differently in females and males, dramatic shifts in our reproductive ecology and environment have led to sex differences in diseases to be more pronounced in urban, industrialized contexts. Under the PCH, we propose that the evolution of eutherian placentation exerted sex-specific selection on female immune function to tolerate fetal antigens while still defending the pregnant individual against pathogens. We theorize that this process is regulated proximately via hormones and mediated genetically by dosage on sex chromosomes, and that today, the mismatch between an ancestral environment and urban industrial environment interacts with this evolved compensatory immune regulation and results in the observed sex differences in disease risk. Finally, a sedentary lifestyle that affects reproductive hormone levels exacerbate these differences. We unpack the interrelated components of the PCH related to shifting reproductive states, parasite loads, and energetic availability, which are particularly relevant for sex differences in human disease.
This work was supported in part by a Wenner-Gren Foundation Dissertation Grant #9466.