ZMYND12 serves as an IDAd subunit that is essential for sperm motility in mice

• DOI: 10.1007/s00018-024-05344-7
• Publication Date: 2024-07-27T07:02:41Z
• Authors: Chang Wang; Qingsong Xie; Xun Xia; Chuanying Zhang; Shan Jiang; Sihan Wang; Xi Zhang; Rong Hua; Jiangyang Xue; Haoyu Zheng
• Keywords: Asthenozoospermia; Capacitation; Axoneme; Immunoprecipitation

AbstractInner dynein arms (IDAs) are formed from a protein complex that is essential for appropriate flagellar bending and beating. IDA defects have previously been linked to the incidence of asthenozoospermia (AZS) and male infertility. The testes-enriched ZMYND12 protein is homologous with an IDA component identified in Chlamydomonas. ZMYND12 deficiency has previously been tied to infertility in males, yet the underlying mechanism remains uncertain. Here, a CRISPR/Cas9 approach was employed to generate Zmynd12 knockout (Zmynd12−/−) mice. These Zmynd12−/− mice exhibited significant male subfertility, reduced sperm motile velocity, and impaired capacitation. Through a combination of co-immunoprecipitation and mass spectrometry, ZMYND12 was found to interact with TTC29 and PRKACA. Decreases in the levels of PRKACA were evident in the sperm of these Zmynd12−/− mice, suggesting that this change may account for the observed drop in male fertility. Moreover, in a cohort of patients with AZS, one patient carrying a ZMYND12 variant was identified, expanding the known AZS-related variant spectrum. Together, these findings demonstrate that ZMYND12 is essential for flagellar beating, capacitation, and male fertility.