Administration of melatonin for prevention of preterm birth and fetal brain injury associated with premature birth in a mouse model

作者：Ji Yeon Lee, Haengseok Song, Oyunbileg Dash, Mira Park, Na Shin, Michael W. McLane, Jun Lei, Jong Yun Hwang, Irina Burd · 发表于：American Journal of Reproductive Immunology · 年份：2019 · DOI：10.1111/aji.13151 · 被引用次数：53 · 研究领域：Circadian rhythm and melatonin、Preterm Birth and Chorioamnionitis、Tryptophan and brain disorders

PROBLEM: Maternal inflammation leads to preterm birth and perinatal brain injury. Melatonin, through its anti-inflammatory effects, has been shown to be protective against inflammation-induced perinatal adverse effects. However, the immunomodulatory effects of melatonin on preterm birth and prematurity-related morbidity remain unknown. We wanted to investigate the effects of maternally administered melatonin on preterm birth and perinatal brain injury in a mouse model of maternal inflammation. METHOD OF STUDY: A model of maternal inflammation employing lipopolysaccharide (LPS) was used to mimic the most common clinical scenario of preterm birth, that of maternal inflammation. Mice were randomly divided into the following groups: control, LPS, and LPS with melatonin pre-treatment. Doppler ultrasonography was used to obtain fetal and maternal hemodynamic measurements in utero. Placenta and fetal brains were harvested and analyzed for proinflammatory markers and signs of perinatal brain injury, respectively. Surviving offspring were assessed for neuromotor outcomes. RESULTS: Melatonin pre-treatment lowered the level of proinflammatory cytokines in the uterus and the placenta, significantly improved LPS-induced acute fetal neuroinflammation and perinatal brain injury, as well as significantly upregulated the SIRT1/Nrf2 signaling pathway to reduce LPS-induced inflammation. Melatonin also prevented adverse neuromotor outcomes in offspring exposed to maternal inflammation. CONCLUSIO...