Single-cell analysis of fetal testis reveals dysfunction of human Leydig cells in Klinefelter syndrome

Research ArticleCell biologyReproductive biology Open Access | 10.1172/JCI201124

Tong Yan,1 Guancheng Chen,1 Jie Zhang,2 Wenjing Jia,3 Nan Lu,4 Shuping Jin,5 Haotian Zhang,1 Yichen Zhao,1 Lu Jiang,5 Jing Wu,6 Qing Liu,6 Chenghao Situ,1 Hui Zhu,1 Yan Li,7 Quan Wang,3 Xiaoyu Yang,4 Chao Qin,8 Xiaofeng Song,3 Qing Cheng,5 and Xuejiang Guo1

1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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1Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

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, Jiangsu, China.

2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

3Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China.

4State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

5Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu, China.

6School of Biomedical Engineering and Informatics and

7Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

8State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Address correspondence to: Xuejiang Guo, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Phone: 86.25.86869383; Email: guo_xuejiang@njmu.edu.cn. Or to: Qing Cheng, Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University, 123 Tianfei Lane, Mochou Road, Nanjing 210004, China. Phone: 86.25.52226846; Email: chengq@njmu.edu.cn. Or to: Xiaofeng Song, Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 28 Jiangjun Avenue, Moling Subdistrict, Nanjing 211100, China. Phone: 86-25-84891938; Email: xfsong@nuaa.edu.cn. Or to: Chao Qin, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 211000, China. Phone: 86.25.83714511; Email: qinchao@njmu.edu.cn.

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

Find articles by Guo, X. in: PubMed | Google Scholar |

Authorship note: TY, GC, JZ, WJ, and NL contributed equally to this work.

Published June 9, 2026 - More info

Published in Volume 136, Issue 14 on July 15, 2026
J Clin Invest. 2026;136(14):e201124. https://doi.org/10.1172/JCI201124.
© 2026 Yan et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Published June 9, 2026 - Version history
Received: October 20, 2025; Accepted: June 2, 2026 View PDF Abstract

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