Transgenerational effect of parental obesity and chronic parental bisphenol A exposure on hormonal profile and reproductive organs of preadolescent Wistar rats of F1 generation: A one-generation study

Hum Exp Toxicol. 2020 Jan;39(1):59-76. doi: 10.1177/0960327119873017. Epub 2019 Sep 11.


There is a global concern about adverse health effects of endocrine-disrupting chemicals (EDCs). Bisphenol A (BPA), an estrogenic and obesogenic compound, used in the plastic and medical industry has a dominant position among EDCs as far as human health and regulatory scenario are concerned. Due to its omnipresence across the biosphere, population of all age groups and health status is unavoidably exposed to BPA. Transgenerational exposure to BPA and its effects have also been recognized. However, there is no report on the transgenerational effect of BPA on metabolically disordered parents, such as obese ones. We studied effect of BPA exposure in F0 generation and its impact on F1 generation and factored parental obesity in transgenerational effect of concurrent exposure to low dose BPA (10 ppm × 180 days) in Wistar rats in a one-generation study protocol. The exposed F0 generation animals were crossed and F1 generation was analyzed 35 days after birth for indications of reproductive toxicity. We observed changes in hormone levels and disturbance in glucose and lipid homeostasis. Animals showed increased serum cholesterol and triglycerides along with higher birth weight and rapid weight gain. Histopathological evidence confirmed the presence of regressive and inflammatory changes in the ovary and testis. The test group showed metabolic disturbances in comparison to control group. Our study showed the additive effect of parental obesity in transgenerational reproductive toxicity of BPA. Female animals of F1 generation of BPA-treated obese parents showed more insulin resistance than males with similar exposure scenario. Our study highlights the confounding role of metabolic disorders such as obesity in the transgenerational toxicity of BPA, which otherwise itself is implicated in the aetiology of such metabolic disorders, directly or indirectly.

Keywords: Bisphenol A; insulin resistance; obesity; polycystic ovarian syndrome; testicular atrophy.

MeSH terms

  • Animals
  • Benzhydryl Compounds / toxicity*
  • Blood Glucose / drug effects
  • Diet, High-Fat
  • Estrogens, Non-Steroidal / toxicity*
  • Female
  • Humans
  • Male
  • Obesity / chemically induced*
  • Obesity / pathology
  • Ovary / drug effects
  • Ovary / pathology
  • Phenols / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Testis / drug effects
  • Testis / pathology
  • Weight Gain / drug effects


  • Benzhydryl Compounds
  • Blood Glucose
  • Estrogens, Non-Steroidal
  • Phenols
  • bisphenol A