HealthNew insights into Klinefelter syndrome and male infertility

New insights into Klinefelter syndrome and male infertility

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New insights into Klinefelter syndrome and male infertility

Imagine the deep frustration of countless men who long to become fathers, only to face infertility due to a genetic condition they can’t control. For those with Klinefelter syndrome, this painful reality is a constant struggle.

How does an extra X chromosome lead to infertility in men? Professor Qiao Jie and her team at Peking University Third Hospital revealed why Klinefelter syndrome, a common genetic condition affecting one in every 600 men, often leads to infertility-;and they’ve identified a potential way to treat it. Their research, titled “How the extra X chromosome impairs the development of male fetal germ cells,” published in Nature Cells (DOI: 10.1038/s41586-024-08104-6) provides new insights into the molecular mechanisms at play and even offers potential treatment avenues.

The problem: Why many men with Klinefelter syndrome can’t have children

Men with Klinefelter syndrome have an extra X chromosome, meaning their genetic makeup is “47, XXY” instead of the usual “46, XY.” They usually lose large amounts of key reproductive cells before puberty. This means they produce very few or no sperm and, until now, have no reliable treatment options. While some can still father children with advanced reproductive technology, nearly half still struggle to find usable sperm.

The research: Examining cells before they are lost

The team studied fetal germ cells (FGCs) from Klinefelter patients, which develop early in life before disappearing. They found that the presence of the extra X chromosome causes both X chromosomes to remain active in fetal germ cells, causing an overload of certain genes. This gene surge disrupts important biological pathways and prevents the cells from maturing properly.

Additionally, these cells could not move to the right location in the testes, which is necessary for them to grow into mature, sperm-producing cells. With abnormal gene activity and disrupted movement, these cells are lost early, well before they can develop into functional sperm.

Key findings and potential treatments

The team found that using TGF-β inhibitors could help these fetal germ cells mature normally, pointing to possible treatments for infertility in men with Klinefelter syndrome. 

With this study, Professor Qiao Jie’s team brings new understanding and hope to men facing infertility, highlighting the significant contributions of Peking University Third Hospital to advancing reproductive health science.

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