Brief postnatal exposure to bisphenol A affects apoptosis and gene expression in the medial prefrontal cortex and social behavior in rats with sex specificity

Neurotoxicology. 2023 Jan:94:126-134. doi: 10.1016/j.neuro.2022.11.011. Epub 2022 Nov 25.


Bisphenol A (BPA) is an endocrine disruptor found in polycarbonate plastics and exposure in humans is nearly ubiquitous and it has widespread effects on cognitive, emotional, and reproductive behaviors in both humans and animal models. In our laboratory we previously found that perinatal BPA exposure results in a higher number of neurons in the adult male rat prefrontal cortex (PFC) and less play in adolescents of both sexes. Here we examine changes in the rate of postnatal apoptosis in the rat prefrontal cortex and its timing with brief BPA exposure. Because an increased number of neurons in the PFC is a characteristic of a subtype of autism spectrum disorder, we tested social preference following brief BPA exposure and also expression of a small group of genes. Males and females were exposed to BPA from postnatal days (P) 6 through 8 or from P10 through 12. Both exposures significantly decreased indicators of cell death in the developing medial prefrontal cortex in male subjects only. Additionally, males exposed to BPA from P6 - 8 showed decreased social preference and decreased cortical expression of Shank3 and Homer1, two synaptic scaffolding genes that have been implicated in social deficits. There were no significant effects of BPA in the female subjects. These results draw attention to the negative consequences following brief exposure to BPA during early development.

Keywords: Autism; BPA; Endocrine disruptor; Shank3; Social preference.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis
  • Autism Spectrum Disorder* / chemically induced
  • Autism Spectrum Disorder* / metabolism
  • Benzhydryl Compounds / metabolism
  • Benzhydryl Compounds / toxicity
  • Disease Models, Animal
  • Endocrine Disruptors* / toxicity
  • Female
  • Gene Expression
  • Male
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Pregnancy
  • Rats
  • Social Behavior


  • Benzhydryl Compounds
  • bisphenol A
  • Endocrine Disruptors