Laboratory of Metabolic Manipulation of Herbivorous Animal Nutrition, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, PR China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, PR China.
Department of Animal Production and Technology, Faculty of Agricultural Sciences and Technologies, Niğde Ömer Halisdemir University, Nigde 51240, Turkey; Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
Ecotoxicol Environ Saf. 2022 Jun 1;237:113550. doi: 10.1016/j.ecoenv.2022.113550. Epub 2022 Apr 26.
Cadmium (Cd) is a major environmental stressor that induces fetal growth restriction (FGR). Also, changes in gut microbiome diversity-which can be modulated positively by melatonin (Mel) have implications on fetal development and placental functions. Therefore, this study aimed to explore whether the role of Mel in counteracting the Cd-induced FGR by regulating placental barrier injury, endoplasmic reticulum stress (ERS) and mitophagy in pregnant mice is mediated-in part- via the gut microbiota modulations. Pregnant mice were intraperitoneally injected with CdCl (5 mg/kg) and Mel (5 mg/kg) once daily, respectively, at the same time from gestational day (GD) 8 to GD18, and then the maternal colon and placental tissues were collected for detection. To investigate the inner relationship between intestinal flora and the protection of Mel on FGR caused by Cd, gut microbiota transplantation (GMT) was carried out from GD0 to GD18 after the removal of intestinal microbiota by antibiotics. Results indicated that Mel relieved barrier injury, ERS and mitophagy in the placenta, and reversed the maternal gut microbiota dysbiosis. The GMT approach suggested a role of intestinal microbiota in placental barrier injury, ERS and mitophagy induced by Cd. Overall, the results highlighted that the intestinal microbiota and gut-placental axis play a central role in the protective effect of Mel against Cd-induced FGR.
镉（Cd）是一种主要的环境应激物，可诱导胎儿生长受限（FGR）。此外，肠道微生物多样性的变化——其可以通过褪黑素（Mel）正向调节——对胎儿发育和胎盘功能有影响。因此，本研究旨在探讨 Mel 通过调节胎盘屏障损伤、内质网应激（ERS）和线粒体自噬来对抗 Cd 诱导的 FGR 的作用是否部分通过调节肠道微生物群来介导。从妊娠第 8 天（GD）到第 18 天（GD），每天分别向怀孕的小鼠腹膜内注射 CdCl（5mg/kg）和 Mel（5mg/kg），然后收集母体结肠和胎盘组织进行检测。为了研究肠道菌群与 Mel 对 Cd 引起的 FGR 的保护之间的内在关系，在使用抗生素去除肠道菌群后，从 GD0 到 GD18 进行了肠道微生物群移植（GMT）。结果表明，Mel 缓解了胎盘的屏障损伤、ERS 和线粒体自噬，并逆转了母体肠道微生物群失调。GMT 方法表明肠道微生物群在 Cd 诱导的胎盘屏障损伤、ERS 和线粒体自噬中起作用。总体而言，这些结果强调了肠道微生物群和肠-胎盘轴在 Mel 对抗 Cd 诱导的 FGR 的保护作用中的核心作用。
