Pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspring

Abstract Background Pregnancy exposure to titanium dioxide nanoparticles (TiO2NPs) is a vital consideration due to their inadvertent ingestion from environmental contamination. The potential health effects of TiO2NPs on the neurodevelopmental process should be seriously concerned in health risk asse...

Full description

Bibliographic Details
Main Authors: Junhao Su, Xinhao Duan, Yu Qiu, Lixiao Zhou, Hongyang Zhang, Min Gao, Yijun Liu, Zhen Zou, Jingfu Qiu, Chengzhi Chen
Format: Article
Language:English
Published: BMC 2021-08-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-021-00967-5
_version_ 1828137073275568128
author Junhao Su
Xinhao Duan
Yu Qiu
Lixiao Zhou
Hongyang Zhang
Min Gao
Yijun Liu
Zhen Zou
Jingfu Qiu
Chengzhi Chen
author_facet Junhao Su
Xinhao Duan
Yu Qiu
Lixiao Zhou
Hongyang Zhang
Min Gao
Yijun Liu
Zhen Zou
Jingfu Qiu
Chengzhi Chen
author_sort Junhao Su
collection DOAJ
description Abstract Background Pregnancy exposure to titanium dioxide nanoparticles (TiO2NPs) is a vital consideration due to their inadvertent ingestion from environmental contamination. The potential health effects of TiO2NPs 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 TiO2NPs remains very limited. Methods In the present study, the pregnant mice were intragastric administered with 150 mg/kg TiO2NPs 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 TiO2NPs 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 TiO2NPs 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 TiO2NPs 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 TiO2NPs 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 TiO2NPs, and call for comprehensive health risk assessment of TiO2NPs on the susceptible population, such as pregnant women. Graphical abstract
first_indexed 2024-04-11T18:13:30Z
format Article
id doaj.art-9cf2e8bd74e34130a411a72c5f3600c5
institution Directory Open Access Journal
issn 1477-3155
language English
last_indexed 2024-04-11T18:13:30Z
publishDate 2021-08-01
publisher BMC
record_format Article
series Journal of Nanobiotechnology
spelling doaj.art-9cf2e8bd74e34130a411a72c5f3600c52022-12-22T04:10:01ZengBMCJournal of Nanobiotechnology1477-31552021-08-0119112110.1186/s12951-021-00967-5Pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspringJunhao Su0Xinhao Duan1Yu Qiu2Lixiao Zhou3Hongyang Zhang4Min Gao5Yijun Liu6Zhen Zou7Jingfu Qiu8Chengzhi Chen9Department of Health Laboratory Technology, School of Public Health and Management, Chongqing Medical UniversityDepartment of Health Laboratory Technology, School of Public Health and Management, Chongqing Medical UniversityDepartment of Neurology, The Affiliated University-Town Hospital of Chongqing Medical UniversityDepartment of Health Laboratory Technology, School of Public Health and Management, Chongqing Medical UniversityDepartment of Health Laboratory Technology, School of Public Health and Management, Chongqing Medical UniversityDepartment of Health Laboratory Technology, School of Public Health and Management, Chongqing Medical UniversityDepartment of Health Laboratory Technology, School of Public Health and Management, Chongqing Medical UniversityMolecular Biology Laboratory of Respiratory Diseases, Institute of Life Sciences, Chongqing Medical UniversityDepartment of Health Laboratory Technology, School of Public Health and Management, Chongqing Medical UniversityDongsheng Lung-Brain Disease Joint Lab, Chongqing Medical UniversityAbstract Background Pregnancy exposure to titanium dioxide nanoparticles (TiO2NPs) is a vital consideration due to their inadvertent ingestion from environmental contamination. The potential health effects of TiO2NPs 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 TiO2NPs remains very limited. Methods In the present study, the pregnant mice were intragastric administered with 150 mg/kg TiO2NPs 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 TiO2NPs 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 TiO2NPs 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 TiO2NPs 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 TiO2NPs 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 TiO2NPs, and call for comprehensive health risk assessment of TiO2NPs on the susceptible population, such as pregnant women. Graphical abstracthttps://doi.org/10.1186/s12951-021-00967-5Titanium dioxide nanoparticlesIntestinal dysbiosisNeurobehavioral impairmentsPregnancy exposure
spellingShingle Junhao Su
Xinhao Duan
Yu Qiu
Lixiao Zhou
Hongyang Zhang
Min Gao
Yijun Liu
Zhen Zou
Jingfu Qiu
Chengzhi Chen
Pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspring
Journal of Nanobiotechnology
Titanium dioxide nanoparticles
Intestinal dysbiosis
Neurobehavioral impairments
Pregnancy exposure
title Pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspring
title_full Pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspring
title_fullStr Pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspring
title_full_unstemmed Pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspring
title_short Pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspring
title_sort pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspring
topic Titanium dioxide nanoparticles
Intestinal dysbiosis
Neurobehavioral impairments
Pregnancy exposure
url https://doi.org/10.1186/s12951-021-00967-5
work_keys_str_mv AT junhaosu pregnancyexposureoftitaniumdioxidenanoparticlescausesintestinaldysbiosisandneurobehavioralimpairmentsthatarenotsignificantpostnatallybutemergeinadulthoodofoffspring
AT xinhaoduan pregnancyexposureoftitaniumdioxidenanoparticlescausesintestinaldysbiosisandneurobehavioralimpairmentsthatarenotsignificantpostnatallybutemergeinadulthoodofoffspring
AT yuqiu pregnancyexposureoftitaniumdioxidenanoparticlescausesintestinaldysbiosisandneurobehavioralimpairmentsthatarenotsignificantpostnatallybutemergeinadulthoodofoffspring
AT lixiaozhou pregnancyexposureoftitaniumdioxidenanoparticlescausesintestinaldysbiosisandneurobehavioralimpairmentsthatarenotsignificantpostnatallybutemergeinadulthoodofoffspring
AT hongyangzhang pregnancyexposureoftitaniumdioxidenanoparticlescausesintestinaldysbiosisandneurobehavioralimpairmentsthatarenotsignificantpostnatallybutemergeinadulthoodofoffspring
AT mingao pregnancyexposureoftitaniumdioxidenanoparticlescausesintestinaldysbiosisandneurobehavioralimpairmentsthatarenotsignificantpostnatallybutemergeinadulthoodofoffspring
AT yijunliu pregnancyexposureoftitaniumdioxidenanoparticlescausesintestinaldysbiosisandneurobehavioralimpairmentsthatarenotsignificantpostnatallybutemergeinadulthoodofoffspring
AT zhenzou pregnancyexposureoftitaniumdioxidenanoparticlescausesintestinaldysbiosisandneurobehavioralimpairmentsthatarenotsignificantpostnatallybutemergeinadulthoodofoffspring
AT jingfuqiu pregnancyexposureoftitaniumdioxidenanoparticlescausesintestinaldysbiosisandneurobehavioralimpairmentsthatarenotsignificantpostnatallybutemergeinadulthoodofoffspring
AT chengzhichen pregnancyexposureoftitaniumdioxidenanoparticlescausesintestinaldysbiosisandneurobehavioralimpairmentsthatarenotsignificantpostnatallybutemergeinadulthoodofoffspring