In vitro exposure of human spermatozoa to bisphenol A induces pro-oxidative/apoptotic mitochondrial dysfunction.
As bisphenol A (BPA) exerts oxidative/pro-apoptotic effects in several cell types, we explored whether the in vitro exposure to BPA could affect human sperm integrity through the induction of pro-oxidative/apoptotic mitochondrial dysfunction. The exposure of motile sperm suspensions to scalar BPA concentrations for 4h produced a decrease in the mitochondrial membrane potential, starting from 300μM. It was associated with an increased mitochondrial generation of superoxide anion, caspase-9 and caspase-3 activation and motility decrement. Vitality decline was observed at BPA≥400μM. Twenty hours exposure to 300μM BPA, but not to lower concentrations, produced a significant loss in sperm vitality associated with a complete sperm immobilization. Finally, 300μM BPA also produced a significant DNA oxidative damage, as revealed by the formation of oxidized base adduct 8-hydroxy-2'-deoxyguanosine. In conclusion, BPA affected human sperm integrity by inducing pro-oxidative/apoptotic mitochondrial dysfunction.
San Raffaele Sulmona Institute, viale dell'agricoltura, 67039, Sulmona, Italy; Andrology Unit, Department of Life, Health and Environment Sciences, University of L'Aquila, 67100, Coppito, L'Aquila, Italy. Electronic address: arcangelobarbonetti@virgilio.it.
Arcangelo
A
Barbonetti
Andrology Unit, Department of Life, Health and Environment Sciences, University of L'Aquila, 67100, Coppito, L'Aquila, Italy.
Chiara
C
Castellini
Andrology Unit, Department of Life, Health and Environment Sciences, University of L'Aquila, 67100, Coppito, L'Aquila, Italy.
Noemi
N
Di Giammarco
Andrology Unit, Department of Life, Health and Environment Sciences, University of L'Aquila, 67100, Coppito, L'Aquila, Italy.
Gaetano
G
Santilli
Andrology Unit, Department of Life, Health and Environment Sciences, University of L'Aquila, 67100, Coppito, L'Aquila, Italy.
Sandro
S
Francavilla
Andrology Unit, Department of Life, Health and Environment Sciences, University of L'Aquila, 67100, Coppito, L'Aquila, Italy.
Felice
F
Francavilla
D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D004249:DNA Damage; D004785:Environmental Pollutants / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D010968:Plasticizers / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects* / Q000502:physiology; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D053148:Caspase 3; D053453:Caspase 9; D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D010968:Plasticizers; D017382:Reactive Oxygen Species; C505407:CASP3 protein, human; C506433:CASP9 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds
8OHdG; Apoptosis; Caspase; DNA damage; Flow cytometry; Mitochondrial membrane potential; ROS; Sperm motility; Sperm viability