Credit: Lingyun Xiong et al.
Recent findings from USC Stem Cell have uncovered how sex hormones play a role in kidney resilience to disease. The findings could help address the sex-related disparities in treatment for kidney diseases and injury.
The researchers identified over 1,000 genes that showed a difference in activity levels between male and female mice. The activity level differences in the proximal tubule, where nutrient reabsorption occurs, were most evident. Female kidneys are known to be more resilient to disease or injury, thus the researchers wanted to uncover what feminizes or masculinizes the organ.
“By exploring how differences emerge in male and female kidneys during development, we can better understand how to address sex-related health disparities for patients with kidney diseases,” said Professor Andy McMahon, the study’s corresponding author.
In the study, published in Developmental Cell, researchers discovered that testosterone was likely the culprit for the disparity in resistance. Two strategies were employed to feminize the male kidneys, castration before puberty to reduce natural testosterone and removal of the androgen receptors that respond to male sex hormones. To further test the hypothesis female kidneys were also masculinized by injecting testosterone into mice that had their ovaries removed before puberty.
To test whether or not the same genes are responsible for kidney differences in humans, the researchers analyzed male and female kidney biopsies. They found a modest overlap of human and mouse genes.
“There is much more work to be done in studying sex-related differences in normal human kidneys,” said McMahon. “Given the divergent outcomes for male and female patients with kidney disease and injury, this line of inquiry is important for making progress toward eventually closing the gap on these sex-related health disparities.”