title: Analysis of the effects of polyphenols on human spermatozoa reveals unexpected impacts on mitochondrial membrane potential, oxidative stress and DNA integrity; implications for assisted reproductive technology.
abstract: The need to protect human spermatozoa from oxidative stress during assisted reproductive technology, has prompted a detailed analysis of the impacts of phenolic compounds on the functional integrity of these cells. Investigation of 16 individual compounds revealed a surprising variety of negative effects including: (i) a loss of mitochondrial membrane potential (Δψm) via mechanisms that were not related to opening of the permeability transition pore but associated with a reduction in thiol expression, (ii) a decline in intracellular reduced glutathione, (iii) the stimulation of pro-oxidant activity including the induction of ROS generation from mitochondrial and non-mitochondrial sources, (iv) stimulation of lipid peroxidation, (v) the generation of oxidative DNA damage, and (vi) impaired sperm motility. For most of the polyphenolic compounds examined, the loss of motility was gradual and highly correlated with the induction of lipid peroxidation (r=0.889). The exception was gossypol, which induced a rapid loss of motility due to its inherent alkylating activity; one consequence of which was a marked reduction in carboxymethyl lysine expression on the sperm tail; a post-translational modification that is known to play a key role in the regulation of sperm movement. The only polyphenols that did not appear to have adverse effects on spermatozoa were resveratrol, genistein and THP at doses below 100μM. These compounds could, therefore, have some therapeutic potential in a clinical setting.
authors.affiliation: Discipline of Biological Sciences and Priority Research Centre for Reproductive Science, Faculty of Science and IT, University of Newcastle, University Drive, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia. Electronic address: John.Aitken@newcastle.edu.au.
authors.forename: R J
authors.initials: RJ
authors.lastname: Aitken
authors.affiliation: Discipline of Biological Sciences and Priority Research Centre for Reproductive Science, Faculty of Science and IT, University of Newcastle, University Drive, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Muscio
authors.affiliation: Discipline of Biological Sciences and Priority Research Centre for Reproductive Science, Faculty of Science and IT, University of Newcastle, University Drive, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Whiting
authors.affiliation: Discipline of Biological Sciences and Priority Research Centre for Reproductive Science, Faculty of Science and IT, University of Newcastle, University Drive, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
authors.forename: H S
authors.initials: HS
authors.lastname: Connaughton
authors.affiliation: Discipline of Biological Sciences and Priority Research Centre for Reproductive Science, Faculty of Science and IT, University of Newcastle, University Drive, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
authors.forename: B A
authors.initials: BA
authors.lastname: Fraser
authors.affiliation: Discipline of Biological Sciences and Priority Research Centre for Reproductive Science, Faculty of Science and IT, University of Newcastle, University Drive, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Nixon
authors.affiliation: Discipline of Biological Sciences and Priority Research Centre for Reproductive Science, Faculty of Science and IT, University of Newcastle, University Drive, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
authors.forename: N D
authors.initials: ND
authors.lastname: Smith
authors.affiliation: Discipline of Biological Sciences and Priority Research Centre for Reproductive Science, Faculty of Science and IT, University of Newcastle, University Drive, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
authors.forename: G N
authors.initials: GN
authors.lastname: De Iuliis
mesh_terms: D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects* / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D059808:Polyphenols / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D027724:Reproductive Techniques, Assisted; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D059808:Polyphenols
keywords: Antioxidant; Mitochondrial membrane potential; Oxidative stress; Polyphenols; Spermatozoa