YKT6 Is Essential for Male Fertility by Promoting Meiosis Progression During Spermatogenesis of Mice

Jie Cen; Xiaochen Yu; Ziqi Wang; Wenbo Liu; Jianze Xu; Qian Fang; Fei Gao; Yongzhi Cao; Hongbin Liu

doi:10.1111/cpr.70079

Cell Proliferation ›› 2026, Vol. 59 ›› Issue (1) :e70079 DOI: 10.1111/cpr.70079

ORIGINAL ARTICLE

YKT6 Is Essential for Male Fertility by Promoting Meiosis Progression During Spermatogenesis of Mice

Jie Cen ¹^,²^,³^,⁴^,⁵^,⁶
, Xiaochen Yu ¹^,²^,⁷
, Ziqi Wang ¹^,²^,⁸
, Wenbo Liu ¹^,²^,³^,⁴^,⁵^,⁶
, Jianze Xu ¹^,²^,³^,⁴^,⁵^,⁶
, Qian Fang ¹^,²^,³^,⁴^,⁵^,⁶
, Fei Gao ¹^,²^,³^,⁴^,⁵^,⁶^,⁹^,¹⁰
, Yongzhi Cao ¹^,²^,³^,⁴^,⁵^,⁶^,¹⁰
, Hongbin Liu ¹^,²^,³^,⁴^,⁵^,⁶^,¹¹

Author information +

¹. Institute of Women, Children and Reproductive Health, Shandong University, China

². State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, Shandong, China

³. National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China

⁴. Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, China

⁵. Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, China

⁶. Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China

⁷. Center for Reproductive Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

⁸. Department of Ultrasound, Qilu Hospital of Shandong University, Jinan, Shandong, China

⁹. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China

¹⁰. Model Animal Research Center, Shandong University, Jinan, Shandong, China

¹¹. CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China

gaof@ioz.ac.cn

yzcao@sdu.edu.cn

hongbin_sduivf@aliyun.com

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Abstract

SNARE proteins are required for membrane fusion events throughout the endomembrane system, and are therefore associated with vesicular transport. Here, we found that the SNARE family member, YKT6, is indispensable for male fertility in mice. Conditional Ykt6 knockout in pre-meiotic and meiotic germ cells leads to complete sterility and meiotic arrest in male mice, which exhibit loss of spermatocytes in seminiferous tubules, but without obvious disruption of chromosomal behaviours during meiosis. We observed that the abundance of syncytia increases along with abnormal morphology of the Golgi apparatus, while lysosomes decrease in Ykt6-cKO testes. Quantitative proteomics and immunofluorescent staining both showed dysregulation of vesicular transport in YKT6-deficient spermatocytes. Additionally, the recombinant mouse proteins, HA::YKT6 and MYC::STX1A, could interact in vitro, further supporting a likely role in mediating transport vesicle fusion with the plasma membrane. Finally, the absence of TEX14 signal within syncytia and enlarged TEX14 rings between spermatocytes together suggest a failure to stabilise intercellular bridges in Ykt6-cKO testes. These results demonstrate that YKT6 is required for male fertility by promoting meiosis progression through vesicular transport regulation during spermatogenesis in mice, expanding our understanding of YKT6 functions, and suggesting a possible strategy for future interventions for male infertility in humans.

Keywords

intercellular bridge / meiotic arrest / spermatogenesis / vesicular transport / YKT6

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Jie Cen, Xiaochen Yu, Ziqi Wang, Wenbo Liu, Jianze Xu, Qian Fang, Fei Gao, Yongzhi Cao, Hongbin Liu. YKT6 Is Essential for Male Fertility by Promoting Meiosis Progression During Spermatogenesis of Mice. Cell Proliferation, 2026, 59(1): e70079 DOI:10.1111/cpr.70079

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