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DNAH14 deficiency impairs sperm motility by reducing flagellar beat amplitude

Liu, Y.; Zhao, Y.; Qiu, Y.; Zeng, J.; Xu, H.; Wu, B.; Tang, X.; Wang, L.; Li, W.; Liu, C.

2025-07-31 developmental biology
10.1101/2025.07.28.667185 bioRxiv
Show abstract

Male infertility affects approximately 15-20% of couples worldwide, with asthenozoospermia accounting for 19% of cases. Nevertheless, the genetic basis of many asthenozoospermia cases remains poorly understood. In this study, we generated Dnah14 knockout mice, which displayed subfertility due to impaired sperm motility despite normal sperm morphology. Comprehensive kinematic analysis revealed that Dnah14-deficient spermatozoa exhibited reduced flagellar beat amplitude but increased beat frequency, while other dynein components remained unaffected. Notably, increasing sperm concentration during in vitro fertilization (IVF) experiments partially rescued the fertilization defects caused by Dnah14 deletion, suggesting a compensatory mechanism for this specific form of asthenozoospermia. Our results establish DNAH14 as a critical regulator of sperm motility and propose a potential therapeutic strategy for affected individuals.

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