Paternal bisphenol a diet changes prefrontal cortex proteome and provokes behavioral dysfunction in male offspring

- We examined effects of paternal BPA diet on prefrontal cortex proteome of male offspring.
- Prefrontal cortical ER stress and myelin deficiency related molecules were changed.
- We observed influences of paternal BPA diet on behaviors of male offspring.
- Paternal BPA exposure alters social and anxiety-like behavior in male mice.

Relatively little attention has been given paternal effects on next generation. Given that Bisphenol A (BPA), a ubiquitous compound in maternal diet, may disrupt brain development and behavior, we hypothesized that paternal BPA diet (PBD) could affect offspring development. Prefrontal cortex (PFC), a vital brain region, is involved in emotion and social behavior. To test whether PBD could alter developing PFC, we carried out a proteomics approach for PFC in male juvenile offspring that responded to PBD (50 mg BPA/kg diet). We found that PBD altered the expressions of binding immunoglobulin protein (BIP), CCAAT/-enhancer-binding protein homologous protein (CHOP) and B-cell lymphoma-2 (BCL-2), which could reflect endoplasmic reticulum (ER) stress. In addition, downregulation of myelinogenesis genes and myelin basic protein (MBP) could provoke myelin deficiency. Furthermore, PBD significantly increased anxiety-like behavior and impaired social behavior in male offspring. Taken together, these results revealed the alterations of ER stress and myelin destruction related molecules induced by PBD might be a potential mechanism for the behavior deficits in their male offspring. These findings remind us of the importance of paternal effects in the further environmental exposure research.