Latest study: X chromosomes influence sexual diseases!

Latest study: X chromosomes influence sexual diseases!

A team of Technical University of Munich (TUM) has found a new approach to explaining gender differences in diseases in old age. Especially when it comes to cardiovascular diseases and neurodegenerative diseases such as dementia and Parkinson's, it is clear that women are affected differently than men. The researchers discovered that in female mice, genes on the silenced second X chromosome become active as they age.

Women have two X chromosomes, one of which is randomly inactivated in each cell. This structure, known as Barr bodies, ensures that there is no double reading of genes in female cells. The Barr corpuscle constricts into a compact structure that can no longer be read. This mechanism is crucial to prevent overactivity of genes on the X chromosome and to compensate for gene dosage between the sexes. An exception to this inactivation are certain genes that can escape silencing and thus cause higher gene activity. These genetic changes are suspected of having an influence on diseases.

The influence of aging

Dr. Daniel Andergassen, group leader at the Institute of Pharmacology and Toxicology at TUM, explains that with increasing age, more and more genes escape the inactivation of the Barr body. This could explain why women experience different health challenges compared to men as they age. The study presenting these findings was published in the journal “Nature Aging” and thus makes an important contribution to understanding the biological basis of gender-specific diseases.

When understanding Barr bodies, it is important to consider their role in human cells. These highly condensed DNA structures are located at the edge of the cell nucleus and are present in many cells, including epithelial cells of the oral, nasal and vaginal mucosa as well as in amniotic cells and fibroblasts. They can be stained with Feulgen reagent or other DNA dyes, which is used for gender diagnosis. For accurate gender analysis, at least 50 Barr bodies must be registered to minimize false negatives. Barr bodies also play an important role in genetic diseases that are associated with an abnormal number of X chromosomes, such as Klinefelter or triple X syndrome. Here all but one of the X-gonosomes are inactivated, which means that the symptoms of the diseases are often milder.

The mechanisms of X inactivation

X-inactivation, also known as “Lyonization,” is an evolutionarily evolved mechanism that allows dose compensation between the sexes. Without this mechanism, female cells would have a double set of genes on the X chromosomes. The first X chromosome has more than 800 protein-coding genes, while the Y chromosome contains just 45 known protein-coding genes. This difference occurred during evolution as the Y chromosome degenerated and lost size.

In summary, research makes it clear that the biochemical and genetic differences between men and women, particularly as we age, can have far-reaching effects on health. The TUM team's results shed light on the complexity of genetic regulation, which is of considerable interest in both basic research and clinical application.