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 C. elegans SDHA orthologue SDHA-2 is essential for male fertility: sdha-2 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 sdha-1 and icl-1 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.
iScience. 2022 Nov 14*** epublish ***
Rachel M Woodhouse, Natalya Frolows, Guoqiang Wang, Azelle Hawdon, Edmund Heng Kin Wong, Linda C Dansereau, Yingying Su, Liam D Adair, Elizabeth J New, Ashleigh M Philp, Wei Kang Tan, Andrew Philp, Alyson Ashe
The University of Sydney, School of Life and Environmental Sciences, Sydney, NSW 2006, Australia., Department of Molecular Biology and Biochemistry, Nelson Biological Laboratories, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA., Garvan Institute of Medical Research, Sydney, NSW 2010, Australia., Sydney Microscopy and Microanalysis, The University of Sydney, Sydney, NSW 2006, Australia., The University of Sydney, School of Chemistry, Sydney, NSW 2006, Australia., St Vincent's Clinical School, UNSW Medicine, University of NSW, Sydney, NSW 2010, Australia., Centre for Healthy Ageing, Centenary Institute, Missenden Road, Sydney, NSW 2050, Australia.