Pregnancy and weaning regulate human maternal liver size and function

Significance

These human data are consistent with reproductive control of liver size and function in women and concur with recent observations in rodents, suggesting a conserved liver biology. The question of whether this described liver biology has implications for maternal health during pregnancy or sex-specific risk for liver disease remains to be determined. However, our evidence suggestive of weaning-induced liver involution in women may lead to improved understanding of the high rates of liver metastasis observed in young postpartum breast cancer patients.

Abstract

During pregnancy, the rodent liver undergoes hepatocyte proliferation and increases in size, followed by weaning-induced involution via hepatocyte cell death and stromal remodeling, creating a prometastatic niche. These data suggest a mechanism for increased liver metastasis in breast cancer patients with recent childbirth. It is unknown whether the human liver changes in size and function during pregnancy and weaning. In this study, abdominal imaging was obtained in healthy women at early and late pregnancy and postwean. During pregnancy time points, glucose production and utilization and circulating bile acids were measured. Independently of weight gain, most women’s livers increased in size with pregnancy, then returned to baseline postwean. Putative roles for bile acids in liver growth and regression were observed. Together, the data support the hypothesis that the human liver is regulated by reproductive state with growth during pregnancy and volume loss postwean. These findings have implications for sex-specific liver diseases and for breast cancer outcomes.