title: Prohibitin involvement in the generation of mitochondrial superoxide at complex I in human sperm.
abstract: Prohibitin (PHB), a major mitochondrial membrane protein, has been shown earlier in our laboratoryto regulate sperm motility via an alteration in mitochondrial membrane potential (MMP) in infertile men with poor sperm quality. To test if PHB expression is associated with sperm mitochondrial superoxide (mROS) levels, here we examined sperm mROS levels, high MMP and lipid peroxidation in infertile men with poor sperm motility (asthenospermia, A) and/or low sperm concentrations (oligoasthenospermia, OA). The diaphorase-type activity of sperm mitochondrial complex I (MCI) and PHB expression were also determined. We demonstrate that mROS and lipid peroxidation levels are significantly higher in sperm from A and OA subjects than in normospermic subjects, whereas high MMP and PHB expression are significantly lower. A positive correlation between mROS and lipid peroxidation and a negative correlation of mROS with PHB expression, high MMP, and sperm motility were found in these subjects. The finding of similar diaphorase-type activity levels of sperm MCI in the three groups studied suggests that the catalytic subunits of MCI in the matrix arm may produce mROS on its own. There may be a dysfunction of electron transport at MCI associated with decreased expression of PHB in sperm with poor quality. We conclude that mROS level is increased and associated with decreased PHB expression, and it may regulate sperm motility via increases in low MMP and lipid peroxidation. This is the first report on the involvement of PHB in human sperm motility loss associated with increased generation of mROS at MCI.
authors: Department of Anatomy, Histology & Embryology, Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of Shanghai, Institute of Reproduction and Development, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Ran-Ran
authors: RR
authors: Chai
authors: Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China.
authors: Guo-Wu
authors: GW
authors: Chen
authors: Institute of Reproduction and Development, Shanghai Medical College, Fudan University, National Population and Family Planning Key Laboratory of Contraceptive Drugs & Devices, Shanghai Institute of Planned Parenthood Research, Shanghai, China.
authors: Hui-Juan
authors: HJ
authors: Shi
authors: School of Biomedical Sciences, The University of Hong Kong, Hong Kong SAR, China.
authors: Wai-Sum
authors: WS
authors: O
authors: Department of Biological Sciences, University of Delaware, Newark, DE, USA.
authors: Patricia A
authors: PA
authors: Martin-DeLeon
authors: Department of Anatomy, Histology & Embryology, Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of Shanghai, Institute of Reproduction and Development, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Hong
authors: H
authors: Chen
mesh_terms: D000328:Adult; D042967:Electron Transport Complex I / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D000091402:Prohibitins; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000494:pharmacology*; D013076:Sperm Count / Q000379:methods; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
chemical_list: C000717328:PHB protein, human; D000091402:Prohibitins; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D013481:Superoxides; D042967:Electron Transport Complex I
keywords: human sperm; mitochondrial ROS; mitochondrial complex I; prohibitin; sperm motility