Paternal bisphenol A exposure induces testis and sperm pathologies in mice offspring: Possibly due to oxidative stress?
A study using Swiss Albino mice was conducted to test the multigenerational effects of bisphenol A (BPA) on sperm quality and testicular architecture, along with identify the molecular mechanisms involved.
In total 18 male mice, 3.5 weeks old, was randomly allocated to 3 groups: Group 1 – no treatment (control), Group 2 – sterile corn oil (vehicle control), Group 3 – BPA (400 μg/ kg) in sterile corn oil, which was injected twice a week for a total of 6 weeks.
At 9.5 weeks of age, the original male mice (generation F0) were allowed to mate with fertile females, who were then separated once impregnated, and allowed to deliver naturally. The delivered pups (generation F1) had their development monitored for the next 10 weeks, before biochemical and histological examination was performed on 6 males aged 11.5 weeks from both F0 and F1 generation.
The mice were monitored for abnormal clinical and behavioral signs, while body and testis weights was also recorded before and after. Sperm analysis and DNA fragmentation testing was carried out along with measurement of oxidative stress, proteins and nitric oxide. Lastly histological analysis of testicular tissue samples was evaluated blind (group not identified), by a histopathologist, to document testis architecture in an unbiased manner.
Initial analysis found that BPA exposure caused abnormalities in the testis of F0 male mice, primarily oxidative injury negatively affecting sperm parameters. Surprisingly the effect on F1 generation mice was even more pronounced implying generational transfer of abnormalities. No difference in survival or mortality rates was observed between the groups along with any signs of acute toxicity. However total body and testis weight was significantly increased in the BPA groups, both F0 and F1 generations, compared to their respective controls.
Interestingly sperm DNA fragmentation was elevated, in the BPA groups, but not elevated enough to reach statistical significance (p > 0.05). On the other hand sperm count and motility was drastically reduced, by over 50% and 30% respectively, with surprisingly no real effect on head morphology, in both F0 and F1 BPA lineage mice.
Oxidative stress measurements, of both lipid and protein peroxidation, also showed significantly elevated levels of MDA and protein carbonyl in the BPA mice for both F0 and F1 generations. Unsurprisingly inflammatory measurements, via Nitric Oxide levels, was also significantly elevated for the BPA lineage mice.
As expected histopathological examination confirmed pathological changes was induced in the testicular tissue, of both F0 and F1 mice, following BPA exposure in generation F0. These changes were more pronounced in F1 mice with visible disorganisation and distortion of seminiferous tubules along with arresting of spermatogenesis.
Overall these results confirm the significant toxicological effect of BPA in F1 generation mice following paternal (F0) exposure.
SUMMARY: EFFECT OF BPA IN MALES
This animal study demonstrated that males exposed to BPA risk significantly reduced sperm counts and motility rates, following an increase in oxidative stress and inflammation. Surprisingly these effects were also observed in the male offspring implying BPA induced changes are transgenerational.
- Mice spermatogenesis is close however not identical
Lombó M, et al. (2019). Genetic and epigenetic alterations induced by bisphenol A exposure during different periods of spermatogenesis: from spermatozoa to the progeny. https://doi.org/10.1038/s41598-019-54368-8
Pan D, et al. (2019). Effects of bisphenol A exposure on DNA integrity and protamination of mouse spermatozoa. https://doi.org/10.1111/andr.12694
Song S, et al. (2014). Perinatal BPA exposure induces hyperglycemia, oxidative stress and decreased adiponectin production in later life of male rat offspring. https://doi.org/10.3390/ijerph110403728
Salian S, et al. (2009). Impairment in protein expression profile of testicular steroid receptor coregulators in male rat offspring perinatally exposed to Bisphenol A. https://doi.org/10.1016/j.lfs.2009.04.005
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