PMID- 32942098 OWN - NLM STAT- MEDLINE DCOM- 20201201 LR - 20201201 IS - 1090-2414 (Electronic) IS - 0147-6513 (Linking) VI - 207 DP - 2021 Jan 1 TI - Altered gut microbiome accompanying with placenta barrier dysfunction programs pregnant complications in mice caused by graphene oxide. PG - 111143 LID - S0147-6513(20)30982-9 [pii] LID - 10.1016/j.ecoenv.2020.111143 [doi] AB - The wide use of graphene oxide (GO) has raised increasing concerns about the potential risks to environmental and human health. Recent studies have shown the vital role of gut microbiome in various pathological status or even exogenous exposure, but more detailed understanding about the effects of possible gut microbiome alterations under GO exposure on reproductive toxicology evaluations in pregnant mammals remained elusive. Here we found that orally administrated GO daily during gestational day (GD) 7-16 caused dose-dependent pregnant complications of mice on the endpoint (GD19), including decreased weight of dam and live fetus, high rate of resorbed embryos and dead fetus, and skeletal development retardation. Meanwhile in placenta tissues of pregnant mice exposed to GO at dose over 10 mg/kg, the expression levels of tight junctions (Claudin1 and Occludin) and vascular endothelial growth factor (VEGFA) decreased approximately by 30%-80%, meaning impaired placenta barrier. According to the data of fecal 16s RNA sequencing in 40 mg/kg dose group and the control group, gut microbiome showed dramatically decreased alpha- and beta-diversity, and upregulated Firmicutes/Bacteroidetes ratio owing to GO exposure. What's more, significantly differentiated abundance of Euryarchaeota is expected to be a special biomarker for failed pregnancy caused by GO. Notably, the result of Spearman correlation analysis suggested that there was a strong link (correlation coefficient>0.6) between perturbed gut microbiome with both abnormally expressed factors of placenta barrier and adverse pregnant outcomes. In summary, the damages of GO exposure to placenta barrier and pregnancy were dose-dependent. And GO exposure was responsible for gut microbiome dysbiosis in mice with pregnant complications. These findings could provide referable evidence to evaluate reproductive risk of GO to mammals. CI - Copyright (c) 2020. Published by Elsevier Inc. FAU - Liu, Xiaojing AU - Liu X AD - Department of Occupational and Environmental Health, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, PR China. FAU - Zhang, Fengmei AU - Zhang F AD - Department of Occupational and Environmental Health, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, PR China. FAU - Wang, Zengjin AU - Wang Z AD - Department of Occupational and Environmental Health, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, PR China. FAU - Zhang, Tongchao AU - Zhang T AD - Department of Occupational and Environmental Health, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, PR China. FAU - Teng, Chuanfeng AU - Teng C AD - School of Chemistry and Chemical Engineering, Shandong University, Qingdao, 266237, PR China. FAU - Wang, Zhiping AU - Wang Z AD - Department of Occupational and Environmental Health, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, PR China. Electronic address: zhipingw@sdu.edu.cn. LA - eng PT - Journal Article DEP - 20200915 PL - Netherlands TA - Ecotoxicol Environ Saf JT - Ecotoxicology and environmental safety JID - 7805381 RN - 0 (Occludin) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (graphene oxide) RN - 7782-42-5 (Graphite) SB - IM MH - Animals MH - Bacteroidetes MH - Dysbiosis MH - Feces MH - Female MH - Fetus MH - Firmicutes MH - Gastrointestinal Microbiome/*drug effects MH - Graphite/*toxicity MH - Humans MH - Mice MH - Occludin/metabolism MH - Placenta/metabolism/*physiology MH - Pregnancy MH - Vascular Endothelial Growth Factor A/metabolism OTO - NOTNLM OT - Graphene oxide OT - Gut microbiome OT - Placenta barrier OT - Pregnant complication EDAT- 2020/09/18 06:00 MHDA- 2020/12/02 06:00 CRDT- 2020/09/17 20:15 PHST- 2020/04/15 00:00 [received] PHST- 2020/08/04 00:00 [revised] PHST- 2020/08/06 00:00 [accepted] PHST- 2020/09/18 06:00 [pubmed] PHST- 2020/12/02 06:00 [medline] PHST- 2020/09/17 20:15 [entrez] AID - S0147-6513(20)30982-9 [pii] AID - 10.1016/j.ecoenv.2020.111143 [doi] PST - ppublish SO - Ecotoxicol Environ Saf. 2021 Jan 1;207:111143. doi: 10.1016/j.ecoenv.2020.111143. Epub 2020 Sep 15.