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Updated: Mar 14, 2026

Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
In vitro exposure of human spermatozoa to bisphenol A induces pro-oxidative/apoptotic mitochondrial dysfunction
Arcangelo Barbonetti1, Chiara Castellini2, Noemi Di Giammarco2
1San 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.
Abstract:
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.
Insights
Bisphenol A (BPA) exposure harms human sperm by causing mitochondrial dysfunction, leading to oxidative stress and apoptosis. This impairs sperm motility and DNA integrity, impacting male fertility.
Area of Science:
- Environmental toxicology
- Reproductive biology
- Mitochondrial dysfunction
Background:
- Bisphenol A (BPA) is a known endocrine disruptor with documented oxidative and pro-apoptotic effects in various cell types.
- Understanding BPA's impact on human sperm is crucial for assessing male reproductive health risks.
Purpose of the Study:
- To investigate the effects of in vitro Bisphenol A (BPA) exposure on human sperm integrity.
- To determine if BPA induces pro-oxidative and apoptotic mitochondrial dysfunction in human sperm.
Main Methods:
- Human sperm suspensions were exposed to varying concentrations of BPA for 4 and 20 hours.
- Assays included mitochondrial membrane potential, superoxide anion generation, caspase activation (caspase-9 and caspase-3), sperm vitality, motility, and DNA oxidative damage (8-hydroxy-2'-deoxyguanosine).
Main Results:
- BPA exposure (≥300μM for 4h) decreased mitochondrial membrane potential, increased superoxide anion generation, activated caspases-9 and -3, and reduced sperm motility.
- Longer exposure (300μM BPA for 20h) led to significant loss of sperm vitality and complete immobilization.
- BPA (300μM) also induced significant DNA oxidative damage.
Conclusions:
- In vitro exposure to Bisphenol A (BPA) negatively affects human sperm integrity.
- BPA induces pro-oxidative and apoptotic mitochondrial dysfunction, leading to decreased sperm motility, vitality, and DNA damage.
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