On March 27, 2025, the selection results of the "Top 10 Scientific Advances in China in 2024" sponsored by the National Natural Science Foundation of China were grandly released at the 2025 Zhongguancun Forum.

　　The research work titled "Multidimensional Effects of Extra X Chromosome on Male Germ Cell Development" completed by the team of Qiao Jie, Yuan Peng, Yan Liying and Wei Yuan from Peking University Third Hospital (PKUTH) was selected among them, marking the third time that Academician Qiao Jie's team has received the honor, following the recognition in 2014 and 2015.

　　The gene expression level of the X chromosome is crucial for reproductive development. Klinefelter syndrome (47, XXY) is the most common genetic cause of male infertility. For decades, the molecular mechanism by which the extra X chromosome impairs the development of male germ cells has remained unsolved. The team's research found that the developmental defects of male germ cells in patients with Klinefelter syndrome begin in the fetal period. The extra X chromosome in their germ cells does not undergo inactivation, leading to an imbalance in the gene expression of the X chromosome. Differentiation genes such as those related to meiosis are inhibited, forcing the cells to remain in an immature state. In addition, the abnormal interaction between germ cells and Sertoli cells will interfere with their coordinated migration and hinder their further differentiation. In vitro experiments have found that inhibiting the TGF-β pathway can promote the differentiation of germ cells. This study not only provides important insights into the pathogenesis of infertility in patients with Klinefelter syndrome but also offers an important theoretical basis for early treatment.

　　Written by: Wu Zhaoxia

　　Edited by: LiuXin

　　Source: Peking University Third Hospital