有动力蛋白轴丝重链基因家族变异的不育男性的有利生育结果

Further evidence from DNAH12 supports favorable fertility outcomes of infertile males with dynein axonemal heavy chain gene family variants     

有动力蛋白轴丝重链基因家族变异的不育男性的有利生育结果

Authors: Geng H, Wang K, Liang D, Ni X, Yu H, Tang D, Lv M, Wu H, Li K, Shen Q, Gao Y, Xu C, Zhou P, Wei Z, Cao Y, Sha Y, Yang X, He X

Source：iScience. 2024 Jun 24;27(7):110366. doi: 10.1016/j.isci.2024.110366.

Abstract

Male infertility is a major concern affecting reproductive health. Biallelic deleterious variants of most DNAH gene family members have been linked to male infertility, with intracytoplasmic sperm injection (ICSI) being an efficacious way to achieve offspring. However, the association between DNAH12 and male infertility is still limited. Here, we identified one homozygous variant and two compound heterozygous variants in DNAH12 from three infertile Chinese men. Semen analysis revealed severe asthenozoospermia, abnormal morphology, and structure of sperm flagella. Furthermore, the Dnah12 knock-out mouse revealed severe spermatogenesis failure and validated the same male infertility phenotype. Favorable fertility outcomes were achieved through ICSI in three human individuals and Dnah12 knock-out mice. Collectively, our study indicated that biallelic variants of DNAH12 can induce male infertility in both human beings and mice. Notably, evidence from DNAH12 enhanced that ICSI was an optimal intervention to achieve favorable fertility outcomes for infertile males with DNAH gene family variants.

Keywords: Genetics; Genomics; Human Genetics; Molecular biology; Reproductive medicine.

摘要

男性不育症是影响生殖健康的一个主要问题。大多数DNAH基因家族成员的双等位基因有害变体与男性不育有关，卵胞浆内单精子注射（ICSI）是获得后代的有效方法。然而，DNAH12与男性不育之间的关联仍然有限。在这里，我们确定了一个纯合子变异和两个复合杂合子变异DNAH12从三个不育的中国男子。精液分析显示严重的弱精子症，精子鞭毛形态和结构异常。此外，Dnah12基因敲除小鼠显示严重的精子发生失败，并验证了相同的男性不育表型。通过ICSI在三个人类个体和Dnah12敲除小鼠中实现了有利的生育结果。总的来说，我们的研究表明，DNAH12的双等位基因变体可以诱导人类和小鼠的男性不育。值得注意的是，来自DNAH12的证据增强了ICSI是具有DNAH基因家族变异的不育男性实现有利生育结果的最佳干预。

关键词：遗传学;基因组学;人类遗传学;分子生物学;生殖医学。