💡 BPA, a pervasive environmental endocrine disruptor, is implicated in fetal growth restriction (FGR). In pregnant ewes, BPA exposure has previously been linked to placental apoptosis, oxidative stress (OS), and reduced placental efficiency, resulting in FGR. However, the interplay between BPA exposure, gut microbiota, and their contribution to placental and intestinal health remain unclear in the context of gestation.
📍 This study aimed to investigate the effects of BPA exposure on maternal placental and intestinal health, elucidate the response of gut microbiota to BPA, and determine the role of gut microbiota in exacerbating BPA-mediated maternal placental apoptosis, autophagy, mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and OS in an ovine model of gestation.
📌 Methods: Pregnant ewes were divided into control (CON) and BPA-exposed groups, receiving either corn oil or BPA (5 mg/kg/day) from gestational day 40 to day 110. Biomarkers of autophagy, apoptosis, mitochondrial dysfunction, ERS, and OS were measured in maternal colonic digesta, ileum, and placental tissues. Gut microbiota transplantation (GMT) from CON and BPA ewes to microbiota-free mice was conducted to assess the role of gut microbiota in BPA-induced effects.
📍 Key Findings:
📌 Placental Efficiency and FGR: BPA exposure led to reduced fetal weights, indicating decreased placental efficiency, and confirming BPA-induced FGR.
📌 Placental and Ileal OS: BPA-exposed ewes exhibited elevated oxidative stress in placental and ileal tissues, evidenced by decreased antioxidant enzyme activity and increased malondialdehyde (MDA) levels.
📌 Mitochondrial Dysfunction: BPA triggered mitochondrial dysfunction in placental and ileal tissues, as indicated by increased ROS production, reduced ATP generation, and altered activities of mitochondrial complexes.
📌 Endoplasmic Reticulum Stress (ERS) and Apoptosis: BPA induced ERS and apoptosis in both placental and ileal tissues, implicating these processes in the pathogenesis of FGR.
📌 Gut Microbiota Dysbiosis: BPA exposure altered the diversity and composition of maternal colonic microbiota, with reductions in beneficial bacteria (𝘉𝘪𝘧𝘪𝘥𝘰𝘣𝘢𝘤𝘵𝘦𝘳𝘪𝘶𝘮, 𝘓𝘢𝘤𝘵𝘰𝘣𝘢𝘤𝘪𝘭𝘭𝘶𝘴, 𝘢𝘯𝘥 𝘣𝘶𝘵𝘺𝘳𝘢𝘵𝘦-𝘱𝘳𝘰𝘥𝘶𝘤𝘪𝘯𝘨 𝘊𝘭𝘰𝘴𝘵𝘳𝘪𝘥𝘪𝘶𝘮) and an increase in 𝘝𝘦𝘪𝘭𝘭𝘰𝘯𝘦𝘭𝘭𝘢 abundance and 𝘍𝘪𝘳𝘮𝘪𝘤𝘶𝘵𝘦𝘴/𝘉𝘢𝘤𝘵𝘦𝘳𝘰𝘪𝘥𝘦𝘵𝘦𝘴 ratio.
📌 Gut Microbiota Transplantation (GMT): Transplantation of gut microbiota from BPA-exposed ewes to microbiota-free mice mirrored the effects observed in the maternal ewes, confirming the role of gut microbiota in BPA-induced placental and ileal effects.
📌 Gut-Placental Axis: The study proposed a gut-placental axis, highlighting the intricate relationship between gut microbiota dysbiosis and BPA-mediated maternal placental apoptosis, OS, and FGR.
📍 This study provides novel insights into the mechanistic link between BPA exposure, gut microbiota dysbiosis, and maternal placental and intestinal health. The findings underscore the potential of modulating gut microbiota through medication or probiotics to alleviate gut-derived placental impairment and FGR. Further research is warranted to explore targeted interventions for mitigating the adverse effects of BPA during pregnancy.
Link to the article : http://tinyurl.com/4pyec9n7