Environmental chemicals play a significant role in the development of metabolic disorders, especially when exposure occurs early in life. We have recently demonstrated that benzene exposure, at concentrations relevant to a cigarette smoke, induces a severe metabolic imbalance in a sex-specific manner affecting male but not female mice. However, the roles of benzene in the development of aberrant metabolic outcomes following gestational exposure, remain largely unexplored. In this study, we exposed pregnant C57BL/6JB dams to benzene at 50 ppm or filtered air for 5 days/week (6h/day from gestational day 1 to birth) and studied male and female offspring metabolic phenotypes in their adult life. While no changes in body weight or body composition were observed between groups, 4-month-old male and female offspring exhibited reduced parameters of energy homeostasis (VO2, VCO2, and heat production). However, only male offspring from benzene-exposed dams were glucose intolerant and insulin resistant at this age. By six months of age, both male and female offspring displayed glucose and insulin intolerance, associated with elevated expression of hepatic gluconeogenesis and inflammatory genes. Additionally, this effect was accompanied by elevated insulin secretion and increased beta-cell mass only in male offspring. Thus, gestational benzene exposure can reprogram offspring for increased susceptibility to the metabolic imbalance in adulthood with differential sensitivity between sexes.

中文翻译：

---

子宫内母体苯暴露引起的代谢重编程

环境化学物质在代谢紊乱的发展中起着重要作用，尤其是在生命早期发生暴露时。我们最近已经证明，与香烟烟雾有关的浓度的苯暴露会以性别特异性的方式引起严重的代谢失衡，从而影响雄性而非雌性小鼠。然而，苯在妊娠暴露后异常代谢结局的发生中所起的作用仍未被充分研究。在这项研究中，我们将怀孕的C57BL / 6JB水坝暴露于浓度为50 ppm的苯或空气中，持续5天/周（从妊娠第1天到出生，每天6h /天），并研究了成年后男性和女性后代的代谢表型。各组之间均未观察到体重或身体组成的变化，4个月大的雄性和雌性后代的能量稳态参数降低（VO2，VCO2和产热）。然而，在这个年龄，只有苯暴露的母坝的雄性后代对葡萄糖不耐，并且对胰岛素具有抗性。到六个月大时，雄性和雌性后代均表现出葡萄糖和胰岛素不耐受性，与肝糖异生和炎症基因表达升高有关。另外，仅在雄性后代中，这种作用伴随着胰岛素分泌增加和β细胞量增加。因此，妊娠苯暴露可以使后代重编程，以增加对成年期代谢不平衡的敏感性，并且两性之间的敏感性不同。在这个年龄，只有苯暴露坝的雄性后代对葡萄糖不耐，并且对胰岛素具有抗性。到六个月大时，雄性和雌性后代均表现出葡萄糖和胰岛素不耐受性，与肝糖异生和炎症基因表达升高有关。另外，仅在雄性后代中，这种作用伴随着胰岛素分泌增加和β细胞量增加。因此，妊娠苯暴露可以使后代重编程，以增加对成年期代谢不平衡的敏感性，并且两性之间的敏感性不同。在这个年龄，只有苯暴露的坝的雄性后代对葡萄糖不耐，并且对胰岛素具有抗性。到六个月大时，雄性和雌性后代均表现出葡萄糖和胰岛素不耐受性，与肝糖异生和炎症基因表达升高有关。另外，仅在雄性后代中，这种作用伴随着胰岛素分泌增加和β细胞量增加。因此，妊娠苯暴露可以使后代重编程以增加对成年期代谢不平衡的敏感性，并且两性之间的敏感性不同。仅在雄性后代中，这种作用伴随着胰岛素分泌的增加和β细胞质量的增加。因此，妊娠苯暴露可以使后代重编程以增加对成年期代谢不平衡的敏感性，并且两性之间的敏感性不同。仅在雄性后代中，这种作用伴随着胰岛素分泌的增加和β细胞质量的增加。因此，妊娠苯暴露可以使后代重编程以增加对成年期代谢不平衡的敏感性，并且两性之间的敏感性不同。