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

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. • Prenatal BPA programmed alterations in the endocrine pancreas of female sheep. • BPA reduced β-cell count, islet insulin in gestational day (GD) 90 fetal pancreata. • BPA increased α-cell count, size, α-to-β-cell ratio, islet glucagon in GD90 fetuses. • Low dose BPA increased islet glucagon, α-to-β-cell ratio, collagen in adult females. • Trends in elevated α-cell count, islet insulin and collagen seen in high BPA adults. [ABSTRACT FROM AUTHOR]