ADGB variants cause asthenozoospermia and male infertility.

Ronggui Qu, Zhihua Zhang, Ling Wu, Qun Li, Jian Mu, Lin Zhao, Zheng Yan, Wenjing Wang, Yang Zeng, Ruyi Liu, Jie Dong, Qiaoli Li, Xiaoxi Sun, Lei Wang, Qing Sang, Biaobang Chen, Yanping Kuang

Human genetics 2023 Jun

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Asthenozoospermia is one of the main factors leading to male infertility, but the genetic mechanisms have not been fully elucidated. Variants in the androglobin (ADGB) gene were identified in an infertile male characterized by asthenozoospermia. The variants disrupted the binding of ADGB to calmodulin. Adgb-/- male mice were infertile due to reduced sperm concentration (< 1 × 106 /mL) and motility. Spermatogenesis was also abnormal, with malformation of both elongating and elongated spermatids, and there was an approximately twofold increase in apoptotic cells in the cauda epididymis. These exacerbated the decline in sperm motility. It is surprising that ICSI with testicular spermatids allows fertilization and eventually develops into blastocyst. Through mass spectrometry, we identified 42 candidate proteins that are involved in sperm assembly, flagella formation, and sperm motility interacting with ADGB. In particular, CFAP69 and SPEF2 were confirmed to bind to ADGB. Collectively, our study suggests the potential important role of ADGB in human fertility, revealing its relevance to spermatogenesis and infertility. This expands our knowledge of the genetic causes of asthenozoospermia and provides a theoretical basis for using ADGB as an underlying genetic marker for infertile males. © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Citation

Ronggui Qu, Zhihua Zhang, Ling Wu, Qun Li, Jian Mu, Lin Zhao, Zheng Yan, Wenjing Wang, Yang Zeng, Ruyi Liu, Jie Dong, Qiaoli Li, Xiaoxi Sun, Lei Wang, Qing Sang, Biaobang Chen, Yanping Kuang. ADGB variants cause asthenozoospermia and male infertility. Human genetics. 2023 Jun;142(6):735-748