PMID- 34362405 OWN - NLM STAT- MEDLINE DCOM- 20220103 LR - 20231101 IS - 1477-3155 (Electronic) IS - 1477-3155 (Linking) VI - 19 IP - 1 DP - 2021 Aug 6 TI - Pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspring. PG - 234 LID - 10.1186/s12951-021-00967-5 [doi] LID - 234 AB - BACKGROUND: Pregnancy exposure to titanium dioxide nanoparticles (TiO(2)NPs) is a vital consideration due to their inadvertent ingestion from environmental contamination. The potential health effects of TiO(2)NPs on the neurodevelopmental process should be seriously concerned in health risk assessment, especially for the pregnant women who are susceptible to the neurodevelopmental toxicity of nano-sized particles. However, the available evidence of neurodevelopmental toxicity of TiO(2)NPs remains very limited. METHODS: In the present study, the pregnant mice were intragastric administered with 150 mg/kg TiO(2)NPs from gestational day (GD) 8 to 21, the maternal behaviors and neurodevelopment-related indicators in offspring were all assessed at different time points after delivery. The gut microbial community in both dams and their offspring were detected by using 16S ribosomal RNA (rRNA) gene sequencing. The gut-brain axis related indicators were also determined in the offspring. RESULTS: The results clearly demonstrated that exposure to TiO(2)NPs did not affect the maternal behaviors of pregnant mice, or cause the deficits on the developmental milestones and perturbations in the early postnatal development of offspring. Intriguingly, our data revealed that pregnancy exposure of TiO(2)NPs did not affect locomotor function, learning and memory ability and anxiety-like behavior in offspring at postnatal day (PD) 21, but resulted in obvious impairments on these neurobehaviors at PD49. Similar phenomena were obtained in the composition of gut microbial community, intestinal and brain pathological damage in offspring in adulthood. Moreover, the intestinal dysbiosis induced by TiO(2)NPs might be highly associated with the delayed appearance of neurobehavioral impairments in offspring, possibly occurring through disruption of gut-brain axis. CONCLUSIONS: This is the first report elucidated that pregnancy exposure to TiO(2)NPs caused delayed appearance of neurobehavioral impairments in offspring when they reached adulthood, although these perturbations did not happen at early life after delivery. These findings will provide valuable insights about neurodevelopmental toxicity of TiO(2)NPs, and call for comprehensive health risk assessment of TiO(2)NPs on the susceptible population, such as pregnant women. CI - (c) 2021. The Author(s). FAU - Su, Junhao AU - Su J AD - Department of Health Laboratory Technology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, People's Republic of China. FAU - Duan, Xinhao AU - Duan X AD - Department of Health Laboratory Technology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, People's Republic of China. FAU - Qiu, Yu AU - Qiu Y AD - Department of Neurology, The Affiliated University-Town Hospital of Chongqing Medical University, Chongqing, 401331, People's Republic of China. FAU - Zhou, Lixiao AU - Zhou L AD - Department of Health Laboratory Technology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, People's Republic of China. FAU - Zhang, Hongyang AU - Zhang H AD - Department of Health Laboratory Technology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, People's Republic of China. FAU - Gao, Min AU - Gao M AD - Department of Health Laboratory Technology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, People's Republic of China. FAU - Liu, Yijun AU - Liu Y AD - Department of Health Laboratory Technology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, People's Republic of China. FAU - Zou, Zhen AU - Zou Z AUID- ORCID: 0000-0002-1651-591X AD - Molecular Biology Laboratory of Respiratory Diseases, Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, People's Republic of China. zouzhen@cqmu.edu.cn. AD - Dongsheng Lung-Brain Disease Joint Lab, Chongqing Medical University, Chongqing, 400016, People's Republic of China. zouzhen@cqmu.edu.cn. FAU - Qiu, Jingfu AU - Qiu J AUID- ORCID: 0000-0003-1220-7319 AD - Department of Health Laboratory Technology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, People's Republic of China. jfqiu@126.com. FAU - Chen, Chengzhi AU - Chen C AUID- ORCID: 0000-0002-1087-4911 AD - Dongsheng Lung-Brain Disease Joint Lab, Chongqing Medical University, Chongqing, 400016, People's Republic of China. chengzhichen@cqmu.edu.cn. AD - Department of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, People's Republic of China. chengzhichen@cqmu.edu.cn. LA - eng GR - 81602820/National Natural Science Foundation of China/ PT - Journal Article DEP - 20210806 PL - England TA - J Nanobiotechnology JT - Journal of nanobiotechnology JID - 101152208 RN - 15FIX9V2JP (titanium dioxide) RN - D1JT611TNE (Titanium) SB - IM MH - Animals MH - Brain-Gut Axis MH - Dysbiosis/*chemically induced MH - Female MH - Gastrointestinal Microbiome/drug effects MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Nanoparticles/*adverse effects MH - Pregnancy MH - Titanium/*adverse effects PMC - PMC8349049 OTO - NOTNLM OT - Intestinal dysbiosis OT - Neurobehavioral impairments OT - Pregnancy exposure OT - Titanium dioxide nanoparticles COIS- The authors deny any competing interests related to this study. EDAT- 2021/08/08 06:00 MHDA- 2022/01/04 06:00 PMCR- 2021/08/06 CRDT- 2021/08/07 05:29 PHST- 2021/05/31 00:00 [received] PHST- 2021/07/17 00:00 [accepted] PHST- 2021/08/07 05:29 [entrez] PHST- 2021/08/08 06:00 [pubmed] PHST- 2022/01/04 06:00 [medline] PHST- 2021/08/06 00:00 [pmc-release] AID - 10.1186/s12951-021-00967-5 [pii] AID - 967 [pii] AID - 10.1186/s12951-021-00967-5 [doi] PST - epublish SO - J Nanobiotechnology. 2021 Aug 6;19(1):234. doi: 10.1186/s12951-021-00967-5.