PMID- 35219956 OWN - NLM STAT- MEDLINE DCOM- 20220315 LR - 20220315 IS - 1090-2414 (Electronic) IS - 0147-6513 (Linking) VI - 233 DP - 2022 Mar 15 TI - A metabolomic study on the effect of prenatal exposure to Benzophenone-3 on spontaneous fetal loss in mice. PG - 113347 LID - S0147-6513(22)00187-7 [pii] LID - 10.1016/j.ecoenv.2022.113347 [doi] AB - Benzophenone-3 (BP-3) is widely used in a variety of cosmetics and is prevalent in drinking water or food, and women were under notable high exposure burden of BP-3. Reports show the associations between prenatal exposure to BP-3 and the risk of fetal loss, but its underlying mechanism remains largely unknown. Pregnant ICR mice were gavaged with BP-3 from gestational day (GD) 0 to GD 6 at doses of 0.1, 10 and 1000 mg/kg/day. The samples were collected on GD 12. Ultra-performance liquid chromatography coupled with mass spectrometry-based metabolomics was used to detect metabolome changes in fetal mice, the uterus and the placenta to identify the underlying mechanism. The results showed that the body weight and relative organ weights of the liver, brain and uterus of pregnant mice were not significantly changed between the control group and the treatment group. BP-3 increased fetal loss, and induced placental thrombosis and tissue necrosis with enhancement of platelet aggregation. Metabolomic analysis revealed that fructose and mannose metabolism, the TCA cycle, arginine and proline metabolism in the fetus, arginine and proline metabolism and biotin metabolism in the uterus, and arginine biosynthesis and pyrimidine metabolism in the placenta were the key changed pathways involved in the above changes. Our study indicates that exposure to BP-3 can induce placental thrombosis and fetal loss via the disruption of maternal and fetal metabolism in mice, providing novel insights into the influence of BP-3 toxicity on the female reproductive system. CI - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Han, Xiumei AU - Han X AD - State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Lu, Ting AU - Lu T AD - State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Wujin District Center for Disease Control and Prevention, Changzhou 213164, China. FAU - Hu, Yanhui AU - Hu Y AD - Department of Public Health, Sir Run Run Hospital, Nanjing Medical University, Nanjing 211166, China. FAU - Duan, Jiawei AU - Duan J AD - State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Guan, Yusheng AU - Guan Y AD - State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Huang, Xiaomin AU - Huang X AD - State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Zhou, Jingjing AU - Zhou J AD - State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Huang, Rui AU - Huang R AD - State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Tang, Miaomiao AU - Tang M AD - State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Sun, Rongli AU - Sun R AD - Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China. FAU - Wang, Ying AU - Wang Y AD - Suzhou Center for Disease Control and Prevention, Suzhou 215004, China. FAU - Song, Ling AU - Song L AD - State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Xia, Yankai AU - Xia Y AD - State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Wang, Xinru AU - Wang X AD - State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Chen, Minjian AU - Chen M AD - State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address: minjianchen@njmu.edu.cn. FAU - Chen, Ting AU - Chen T AD - State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Nanjing Maternity and Child Health Care Institute, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing 210004, China. Electronic address: chenting@njmu.edu.cn. LA - eng PT - Journal Article DEP - 20220224 PL - Netherlands TA - Ecotoxicol Environ Saf JT - Ecotoxicology and environmental safety JID - 7805381 RN - 0 (Benzophenones) RN - 95OOS7VE0Y (oxybenzone) SB - IM MH - Animals MH - Benzophenones MH - Female MH - Fetus MH - Metabolomics MH - Mice MH - Mice, Inbred ICR MH - *Placenta MH - Pregnancy MH - *Prenatal Exposure Delayed Effects OTO - NOTNLM OT - Benzophenone-3 OT - Metabolomics OT - Spontaneous fetal loss EDAT- 2022/02/28 06:00 MHDA- 2022/03/16 06:00 CRDT- 2022/02/27 20:30 PHST- 2021/11/19 00:00 [received] PHST- 2022/02/08 00:00 [revised] PHST- 2022/02/21 00:00 [accepted] PHST- 2022/02/28 06:00 [pubmed] PHST- 2022/03/16 06:00 [medline] PHST- 2022/02/27 20:30 [entrez] AID - S0147-6513(22)00187-7 [pii] AID - 10.1016/j.ecoenv.2022.113347 [doi] PST - ppublish SO - Ecotoxicol Environ Saf. 2022 Mar 15;233:113347. doi: 10.1016/j.ecoenv.2022.113347. Epub 2022 Feb 24.