Growing evidence suggests that environmental disruptors of maternal microbes may have significant detrimental consequences for the developing fetus. Antibiotic exposure during early life can have long-term effects on neurodevelopment in mice and humans. Here we explore whether exposure to low-dose penicillin during only the last week of gestation in mice has long-term effects on offspring behaviour, brain, immune function, and gut microbiota. We found that this treatment had sex-specific effects in the adult mouse offspring. Female, but not male, mice demonstrated decreased anxiety-like behaviours, while male, but not female, mice had abnormal social behaviours which correlated with altered brain expression of AVPR1A, AVPR1B, and OXTR, and decreases in the balance of splenic FOXP3+ regulatory T cells. Prenatal penicillin exposure also led to distinct microbiota compositions that clustered differently by sex. These data suggest that exposure of pregnant mice to even a low dose of penicillin through only the last week before birth is nonetheless sufficient to induce long-term sex-specific developmental changes in both male and female offspring.

中文翻译：

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产前低剂量青霉素导致小鼠行为、免疫调节和肠道微生物群的长期性别特异性变化

越来越多的证据表明，母体微生物的环境破坏者可能对发育中的胎儿产生严重的不利后果。生命早期接触抗生素会对小鼠和人类的神经发育产生长期影响。在这里，我们探讨了小鼠仅在妊娠最后一周接触低剂量青霉素是否会对后代行为、大脑、免疫功能和肠道微生物群产生长期影响。我们发现这种治疗对成年小鼠后代具有性别特异性影响。雌性而非雄性小鼠表现出减少的焦虑样行为，而雄性而非雌性小鼠的社交行为异常，这与 AVPR1A、AVPR1B 和 OXTR 的大脑表达改变有关，以及脾 FOXP3+ 调节性 T 的平衡降低细胞。产前青霉素暴露也导致了不同的微生物群组成，它们按性别聚集在一起。这些数据表明，怀孕小鼠即使在出生前最后一周接触低剂量的青霉素也足以诱导雄性和雌性后代的长期性别特异性发育变化。