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.

中文翻译：

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发育规划：妊娠期 BPA 暴露导致母羊胰岛受损的探索性分析

发育过程中接触双酚 A (BPA) 等内分泌干扰物可能会导致晚年代谢功能障碍。利用独特的绵羊发育编程模型，我们对 BPA 对内分泌胰腺的编程效应进行了探索性分析。怀孕母羊在妊娠日 (GD) 30-90 期间注射环境相关剂量的 BPA，并对雌性胎儿和成年后代的胰腺进行分析。产前接触 BPA 会导致胰岛胰岛素染色和 β 细胞计数减少、胰高血糖素染色和 α 细胞计数增加以及 α 细胞/β 细胞比率增加。在 GD90 评估的胎儿胰腺和暴露于最低 BPA 剂量的成年后代中，结果最为一致。虽然未在胎儿中进行评估，但成人胰岛纤维化有所增加。总的来说，这些数据进一步证明生命早期接触 BPA 可能对人类代谢健康构成威胁。未来的研究应该证实这些发现并破译 BPA 发育内分泌毒性的分子机制。