Woodhouse Rachel M, Frolows Natalya, Wang Guoqiang, Hawdon Azelle, Wong Edmund Heng Kin, Dansereau Linda C, Su Yingying, Adair Liam D, New Elizabeth J, Philp Ashleigh M, Tan Wei Kang, Philp Andrew, Ashe Alyson
The University of Sydney, School of Life and Environmental Sciences, Sydney, NSW 2006, Australia.
Division of Genome Science and Cancer, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia.
iScience. 2022 Nov 14;25(12):105573. doi: 10.1016/j.isci.2022.105573. eCollection 2022 Dec 22.
Mitochondrial health is crucial to sperm quality and male fertility, but the precise role of mitochondria in sperm function remains unclear. SDHA is a component of the succinate dehydrogenase (SDH) complex and plays a critical role in mitochondria. In humans, SDH activity is positively correlated with sperm quality, and mutations in SDHA are associated with Leigh Syndrome. Here we report that the SDHA orthologue SDHA-2 is essential for male fertility: mutants produce dramatically fewer offspring due to defective sperm activation and motility, have hyperfused sperm mitochondria, and disrupted redox balance. Similar sperm motility defects in and mutant animals suggest an imbalance in metabolites may underlie the fertility defect. Our results demonstrate a role for SDHA-2 in sperm motility and male reproductive health and establish an animal model of SDH deficiency-associated infertility.
线粒体健康对精子质量和男性生育能力至关重要，但线粒体在精子功能中的具体作用仍不清楚。SDHA是琥珀酸脱氢酶（SDH）复合体的一个组成部分，在线粒体中发挥关键作用。在人类中，SDH活性与精子质量呈正相关，SDHA突变与 Leigh 综合征有关。在此我们报告，SDHA同源物SDHA-2对雄性生育至关重要：由于精子激活和运动能力缺陷，突变体产生的后代数量大幅减少，精子线粒体过度融合，氧化还原平衡被破坏。以及突变动物中类似的精子运动缺陷表明代谢物失衡可能是生育缺陷的基础。我们的结果证明了SDHA-2在精子运动和男性生殖健康中的作用，并建立了与SDH缺乏相关不孕症的动物模型。
