A mismatch — between the ancestral immune function changes induced by the placenta and fewer modern-day pregnancies — may help explain the greater risk for multiple sclerosis (MS) and other autoimmune diseases in women in industrialized societies, according to a new study.
The shift toward a sedentary lifestyle may further explain these gender differences.
The research with those findings, “The Pregnancy Pickle: Evolved Immune Compensation Due to Pregnancy Underlies Sex Differences in Human Diseases,” was published in the journal Trends in Genetics.
While women are substantially more susceptible to develop autoimmune diseases such as MS and lupus, men are at a higher risk of cancers such as melanoma and colon cancer. Differences in treatment effectiveness also exist, with women responding more favorably to cancer immunotherapies.
Reproductive hormones or environmental exposures alone cannot explain this distinction between genders. Differences in genes on sex chromosomes are independent of reproductive hormones, and could be key contributing factors. Yet, these sex differences remain largely unexplained.
“We are proposing a new theory called the Pregnancy Compensation Hypothesis,” Melissa Wilson, PhD, the study’s senior author, said in a press release written by Sandra Leander.
Her team at Arizona State University hypothesized that women’s ancestral immune system was shaped to facilitate their survival in the presence of the placenta, which induces anti-inflammatory changes to tolerate fetal antigens, while still allowing protection from disease-causing parasites and pathogens.
Both reproductive hormones and heritable variations in sex chromosome content mediate these differences in immune function.