Developmental programming: An exploratory analysis of pancreatic islet compromise in female sheep resulting from gestational BPA exposure

Mol Cell Endocrinol. 2024 Jul 1:588:112202. doi: 10.1016/j.mce.2024.112202. Epub 2024 Mar 27.

Abstract

Developmental exposure to endocrine disruptors like bisphenol A (BPA) are implicated in later-life metabolic dysfunction. Leveraging a unique sheep model of developmental programming, we conducted an exploratory analysis of the programming effects of BPA on the endocrine pancreas. Pregnant ewes were administered environmentally relevant doses of BPA during gestational days (GD) 30-90, and pancreata from female fetuses and adult offspring were analyzed. Prenatal BPA exposure induced a trend toward decreased islet insulin staining and β-cell count, increased glucagon staining and α-cell count, and increased α-cell/β-cell ratio. Findings were most consistent in fetal pancreata assessed at GD90 and in adult offspring exposed to the lowest BPA dose. While not assessed in fetuses, adult islet fibrosis was increased. Collectively, these data provide further evidence that early-life BPA exposure is a likely threat to human metabolic health. Future studies should corroborate these findings and decipher the molecular mechanisms of BPA's developmental endocrine toxicity.

Keywords: Alpha-cell; Beta-cell; Endocrine-disrupting chemicals; Fibrosis; Glucagon; Insulin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds* / toxicity
  • Endocrine Disruptors / toxicity
  • Female
  • Fetus / drug effects
  • Glucagon-Secreting Cells / drug effects
  • Glucagon-Secreting Cells / metabolism
  • Glucagon-Secreting Cells / pathology
  • Insulin / metabolism
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Islets of Langerhans* / drug effects
  • Islets of Langerhans* / metabolism
  • Islets of Langerhans* / pathology
  • Maternal Exposure / adverse effects
  • Phenols* / toxicity
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / chemically induced
  • Prenatal Exposure Delayed Effects* / pathology
  • Sheep

Substances

  • Benzhydryl Compounds
  • bisphenol A
  • Phenols
  • Endocrine Disruptors
  • Insulin