2 of the genes– Gsta4 in red and Cyp4a14 in green– that are more active in female mouse kidneys (blue). Credit: Jing Liu/McMahon Lab
Kidneys in females have been observed to be more resistant to illness and damage. Males require not despair. Recent research led by USC Stem Cell and published in Developmental Cell clarifies how gender hormonal agents affect the variations in kidney resilience in between female and male mice. The research study also illustrates that minimizing testosterone levels can “feminize” the kidney in males, possibly improving its capability to endure injuries and ailments.
” By exploring how differences emerge in male and female kidneys during development, we can much better understand how to address sex-related health disparities for clients with kidney illness,” said Professor Andy McMahon, the research studys matching author, and the director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at the Keck School of Medicine of USC.
Authors Lingyun “Ivy” Xiong and Jing Liu from the McMahon Lab and their partners identified more than 1,000 genes with different levels of activity in female and male mouse kidneys, in a study supported by the National Institutes of Health. The differences were most obvious in the area of the kidneys filtering system known as the proximal tubule, accountable for reabsorbing the majority of the nutrients such as glucose and amino acids back into the bloodstream. The majority of these sex distinctions in gene activity became the mice got in puberty and became much more pronounced as they reached sexual maturity.
Due to the fact that female kidneys tend to fare better in the face of illness or injury, the scientists had an interest in how the gene activity of kidneys becomes “feminized” or “masculinized”– and testosterone seemed the most significant culprit.
To feminize the kidneys of male mice, two methods worked similarly well: castrating males before adolescence and thus reducing their natural testosterone levels, or getting rid of the cellular sensors called androgen receptors that respond to male sex hormones.
Intriguingly, three months of calorie constraint– which is an indirect way to lower testosterone– produced a similar effect. Accordingly, calorie constraint has already been revealed to mitigate certain types of kidney injuries in mice.
To re-masculinize the kidneys of the castrated males, the scientists just required to inject testosterone. Testosterone injection masculinized the kidneys of women who had their ovaries eliminated before the age of puberty.
The researchers performed some similar explores mouse livers. This organ also shows sex-related differences, the hormones and underlying factors driving these distinctions are very various than those at play in the kidney. This suggests that these sex-related organ differences emerged independently during evolution.
To test whether the very same genes are associated with sex-related kidney distinctions in human beings, the researchers evaluated a restricted number of male and female donor kidneys and biopsies. When it pertained to genes that differed in their activity between the sexes, there was a modest overlap of the human genes with the mouse genes.
” There is much more work to be performed in studying sex-related distinctions in regular human kidneys,” stated McMahon. “Given the divergent results for female and male clients with kidney disease and injury, this line of questions is necessary for making development towards eventually closing the gap on these sex-related health disparities.”
Reference: “Direct androgen receptor control of sexually dimorphic gene expression in the mammalian kidney” by Lingyun Xiong, Jing Liu, Seung Yub Han, Kari Koppitch, Jin-Jin Guo, Megan Rommelfanger, Zhen Miao, Fan Gao, Ingileif B. Hallgrimsdottir, Lior Pachter, Junhyong Kim, Adam L. MacLean and Andrew P. McMahon, 5 September 2023, Developmental Cell.DOI: 10.1016/ j.devcel.2023.08.010.
Extra authors are Kari Koppitch, Jin-Jin Guo, Megan Rommelfanger, and Adam L. MacLean from USC; Zhen Miao and Junhyong Kim from the University of Pennsylvania; Fan Gao, Ingileif B. Hallgrimsdottir, and Lior Pachter from the California Institute of Technology.
One hundred percent of this work was supported by federal financing from the National Institutes of Health (grants R01DK126925 and R35GM143019) and the National Science Foundation (DMS2045327).
Kidneys in females have actually been observed to be more resistant to disease and damage. Current research led by USC Stem Cell and released in Developmental Cell sheds light on how gender hormonal agents affect the variations in kidney resilience between female and male mice. The study likewise illustrates that minimizing testosterone levels can “feminize” the kidney in males, possibly enhancing its capability to hold up against injuries and ailments.
Authors Lingyun “Ivy” Xiong and Jing Liu from the McMahon Lab and their partners recognized more than 1,000 genes with different levels of activity in male and female mouse kidneys, in a study supported by the National Institutes of Health.