Female-Male Cardiac Disparities Observed at Embryonic Stage

UNC School of Medicine and Princeton scientists have discovered differences in how particular proteins in heart cells are expressed in genetically diverse male and female mice during the earliest embryonic stage. Their study, published in Development Cell, suggests that male-female differences in protein expression occur immediately after embryonic cells become cardiomyocytes.

“Our studies show that sex biases in heart development occur prior to primary sex determination and can be, and are, associated with sex bias congenital heart disease,” said co-senior author Frank Conlon. “Since sex disparities have been reported in many other disease states, including cancer, dementia, chronic kidney disease, obesity, autoimmune disease, and COVID-19, our studies provide a framework for uncovering the mechanisms and pathways of these disease states, as well.”

The team led a systems-based approach to identify the molecular differences, at both the RNA and protein levels of cells, between male and female embryonic and adult hearts in mice. Conlon’s team then defined the cell types that express a subset of these proteins to show differences in expression in the cardiomyocyte lineage between male and female hearts.  

“Contrary to the current paradigm, we discovered that male-female cardiac sex differences are not solely controlled by hormones but also through a sex chromosome mechanism independent of sex hormones,” said Conlon. “Our analysis showed that protein expression differs between male and female hearts at the embryonic period prior to primary sex determination and prior to the embryo being exposed to sex hormones.”