Preterm birth is a major contributor to early and delayed physical and cognitive impairment. Epidemiological and experimental data indicate that maternal infections are a significant and preventable cause of preterm birth. Recently, melatonin has been suggested to exert neuroprotective effects in several models of brain injury. Here, we sought to investigate whether the administration of melatonin is able to prevent lipopolysaccharide (LPS)‐induced fetal brain damage in a model of LPS‐induced preterm labor. For this purpose, 15‐day pregnant BALB/c mice received intraperitoneally 2 doses of LPS or vehicle: the first one at 10:00 hours (0.26 mg/kg) and the second at 13:00 hours (0.52 mg/kg). On day 14 of pregnancy, a group of mice was subcutaneously implanted with a pellet of 25 mg melatonin. This experimental protocol resulted in 100% of preterm birth and pup death in the LPS group and a 50% of term birth and pup survival in the melatonin + LPS group. In the absence of melatonin, fetuses from LPS‐treated mothers showed histological signs of brain damage, microglial/macrophage activation, and higher levels of IL‐1β, inducible nitric oxide synthase (NOS), and neuronal NOS mRNAs as well as increased histone acetyltransferase activity and histone H3 hyperacetylation. In contrast, antenatal administration of melatonin prevented LPS‐induced fetal brain damage. Moreover, when behavioral traits were analyzed in the offspring from control, melatonin, and melatonin + LPS, no significant differences were found, suggesting that melatonin prevented LPS‐induced long‐term neurodevelopmental impairments. Collectively, our results suggest that melatonin could be a new therapeutic tool to prevent fetal brain damage and its long‐term consequences induced by maternal inflammation.

中文翻译：

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产妇褪黑激素对脂多糖治疗小鼠的后代产生短期和长期的神经保护作用

早产是导致早期和延迟的身体和认知障碍的主要因素。流行病学和实验数据表明，产妇感染是早产的重要且可预防的原因。最近，褪黑激素已被建议在几种脑损伤模型中发挥神经保护作用。在这里，我们试图研究在LPS引起的早产模型中，褪黑激素的给药是否能够预防脂多糖（LPS）引起的胎儿脑损伤。为此目的，怀孕15天的BALB / c小鼠腹膜内接受2剂LPS或媒介物：第1剂在10:00小时（0.26 mg / kg），第二种在13:00小时（0.52 mg / kg）。在怀孕的第14天，一组小鼠皮下植入了25 mg褪黑激素沉淀。该实验方案在LPS组中导致了100％的早产和幼仔死亡，在褪黑素+ LPS组中导致了50％的足月生和幼仔存活。在缺乏褪黑激素的情况下，接受LPS治疗的母亲的胎儿表现出脑损伤，小胶质细胞/巨噬细胞激活，高水平的IL-1β，诱导型一氧化氮合酶（NOS）和神经元NOS mRNA的组织学迹象，以及组蛋白乙酰转移酶升高活性和组蛋白H3过度乙酰化。相反，产前服用褪黑激素可预防LPS诱导的胎儿脑损伤。此外，在对照，褪黑素和褪黑素+ LPS的后代中分析行为特征时，未发现明显差异，这表明褪黑素可预防LPS引起的长期神经发育障碍。总的来说，