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ResearchIn-Press PreviewCell biologyReproductive biology
Open Access |
10.1172/JCI201124
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Yan, T. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Chen, G. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Zhang, J. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Jia, W. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Lu, N. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Jin, S. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Zhang, H. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Zhao, Y. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Jiang, L. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Wu, J. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Liu, Q. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Situ, C. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Zhu, H. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Li, Y. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Wang, Q. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Yang, X. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Qin, C. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Song, X. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Find articles by Cheng, Q. in: PubMed | Google Scholar
1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
6School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
8Department of Urology, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Guo, X.
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Published June 9, 2026 - More info
Klinefelter syndrome (KS), the most common sex chromosome aneuploidy (affecting approximately 1 in 650 live male births), causes severe infertility. The extra X chromosome can impair the development of fetal germ cells, but its effects on somatic cells, especially the Leydig cells, are still not well known. We performed single-cell transcriptome analysis of fetal KS and control testicular cells, and found that two clusters of KS Sertoli cells with the XIST-negative cluster showing distinct gene expression pattern and abnormally increased G2/M ratio. Fetal KS Leydig cells showed increased proliferation and immature differentiation with high level of MAPK signaling pathway and X-linked EIF1AX. Inhibition of MAPK signaling partially rescued overproliferation and defective differentiation and androgen secretion in KS Leydig cells, while overexpression of EIF1AX recapitulated the phenotype of increased proliferation and decline in testosterone synthesis capacity in the Leydig cell line. These findings revealed the early pathological mechanisms of KS somatic cells, and lay the groundwork for developing novel early intervention strategies.