New research uncovers potential treatment for Klinefelter syndrome infertility, highlighting molecular mechanisms and using TGF-β inhibitors to aid sperm production.

Klinefelter’s syndrome, a common genetic disorder affects one in every 600 men leading to infertility (1^✔ ✔Trusted Source
How the extra X chromosome impairs the development of male fetal germ cells

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New research conducted by Professor Qiao Jie and her team at Peking University Third Hospital has found a potential way to treat the condition. The study published in Nature Cells highlights the molecular mechanisms and treatment strategies.

Why Klinefelter’s Syndrome Causes Infertility

Men with Klinefelter’s 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 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.

New Treatment for Klinefelter’s Syndrome Infertility

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.
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’s 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.

1. How the extra X chromosome impairs the development of male fetal germ cells – (https://www.nature.com/articles/s41586-024-08104-6)

Source-Eurekalert