PMID- 31672369 OWN - NLM STAT- MEDLINE DCOM- 20200302 LR - 20211204 IS - 1873-6424 (Electronic) IS - 0269-7491 (Linking) VI - 256 DP - 2020 Jan TI - Microcystin-LR exposure decreased the fetal weight of mice by disturbance of placental development and ROS-mediated endoplasmic reticulum stress in the placenta. PG - 113362 LID - S0269-7491(19)32811-8 [pii] LID - 10.1016/j.envpol.2019.113362 [doi] AB - The placenta is essential for sustaining the growth of the fetus. The aim of this study was to investigate the role of the placenta in MCLR-induced significant reduction in fetal weight, especially the changes in placental structure and function. Pregnant mice were intraperitoneally injected with MCLR (5 or 20 mug/kg) from gestational day (GD) 13 to GD17. The results showed MCLR reduced fetal weight and placenta weight. The histological specimens of the placentas were taken for light and electron microscopy studies. The internal space of blood vessels decreased obviously in the placental labyrinth layer of mice treated with MCLR. After the ultrastructural examination, the edema and intracytoplasmic vacuolization, dilation of the endoplasmic reticulum and corrugation of the nucleus were observed. In addition, maternal MCLR exposure caused a reduction of 11beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) expression in placentae, a critical regulator of fetal development. Several genes of placental growth factors, such as Vegfalpha and Pgf and several genes of nutrient transport pumps, such as Glut1 and Pcft were depressed in placentas of MCLR-treated mice, however nutrient transporters Fatp1 and Snat4 were promoted. Moreover, significant increases in malondialdehyde (MDA) revealed the occurrence of oxidative stress caused by MCLR, which was also verified by remarkable decrease in the glutathione levels, total antioxidant capacity (T-AOC) as well as the activity of antioxidant enzymes. Real-time PCR and western blot analysis revealed that GRP78, CHOP, XBP-1, peIF2alpha and pIRE1 were remarkable increased in placentas of MCLR-treated mice, indicating that endoplasmic reticulum (ER) stress pathway was activated by MCLR. Furthermore, oxidative stress and ER stress consequently triggered apoptosis which contributed to the impairment of placental development. Collectively, these results suggest maternal MCLR exposure results in reduced fetal body weight, which might be associated with ROS-mediated endoplasmic reticulum stress and impairment in placental structure and function. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Zhao, Sujuan AU - Zhao S AD - School of Public Health, Anhui Medical University, Hefei, 230032, China. FAU - Zhong, Shengzheng AU - Zhong S AD - School of Public Health, Anhui Medical University, Hefei, 230032, China. FAU - Wang, Fang AU - Wang F AD - School of Public Health, Anhui Medical University, Hefei, 230032, China. FAU - Wang, Honghui AU - Wang H AD - School of Public Health, Anhui Medical University, Hefei, 230032, China. FAU - Xu, Dexiang AU - Xu D AD - School of Public Health, Anhui Medical University, Hefei, 230032, China. Electronic address: xudex@126.com. FAU - Li, Guangyu AU - Li G AD - College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China. Electronic address: liguangyu@mail.hzau.edu.cn. LA - eng PT - Journal Article DEP - 20191011 PL - England TA - Environ Pollut JT - Environmental pollution (Barking, Essex : 1987) JID - 8804476 RN - 0 (Endoplasmic Reticulum Chaperone BiP) RN - 0 (Hspa5 protein, mouse) RN - 0 (Marine Toxins) RN - 0 (Microcystins) RN - 0 (Reactive Oxygen Species) RN - EQ8332842Y (cyanoginosin LR) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Endoplasmic Reticulum Chaperone BiP MH - Endoplasmic Reticulum Stress/*drug effects MH - Female MH - Fetal Development/*drug effects MH - Fetal Weight/*drug effects MH - Gestational Age MH - Marine Toxins MH - Maternal Exposure/adverse effects MH - Mice MH - Mice, Inbred ICR MH - Microcystins/*toxicity MH - Placenta/*drug effects/metabolism/pathology MH - Pregnancy MH - Reactive Oxygen Species/metabolism OTO - NOTNLM OT - Endoplasmic reticulum stress OT - MCLR OT - Oxidative stress OT - Placental development EDAT- 2019/11/02 06:00 MHDA- 2020/03/03 06:00 CRDT- 2019/11/02 06:00 PHST- 2019/07/12 00:00 [received] PHST- 2019/09/23 00:00 [revised] PHST- 2019/10/07 00:00 [accepted] PHST- 2019/11/02 06:00 [pubmed] PHST- 2020/03/03 06:00 [medline] PHST- 2019/11/02 06:00 [entrez] AID - S0269-7491(19)32811-8 [pii] AID - 10.1016/j.envpol.2019.113362 [doi] PST - ppublish SO - Environ Pollut. 2020 Jan;256:113362. doi: 10.1016/j.envpol.2019.113362. Epub 2019 Oct 11.