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

## TL;DR

YKT6 is crucial for male fertility in mice by supporting meiosis during sperm production through proper vesicular transport.

## Contribution

This study reveals YKT6's essential role in male fertility by regulating vesicular transport during meiosis in mice.

## Key findings

- Conditional knockout of Ykt6 in germ cells causes sterility and meiotic arrest in male mice.
- YKT6 deficiency disrupts vesicular transport and intercellular bridge stability in spermatocytes.
- YKT6 interacts with STX1A, suggesting a role in vesicle fusion during spermatogenesis.

## 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.

Specifically ablating Ykt6 in pre‐meiotic germ cells and meiotic spermatocytes leads to complete sterility and meiotic arrest in conditional knockout male mice. YTK6 is required for stabilising intercellular bridges between spermatocytes due to its key role in maintaining protein homeostasis and vesicular transport‐dependent functions in spermatocytes, without impeding meiotic chromosomal behaviours.