PMID- 29440900 OWN - NLM STAT- MEDLINE DCOM- 20180425 LR - 20220318 IS - 1178-2013 (Electronic) IS - 1176-9114 (Print) IS - 1176-9114 (Linking) VI - 13 DP - 2018 TI - Gestational exposure to titanium dioxide nanoparticles impairs the placentation through dysregulation of vascularization, proliferation and apoptosis in mice. PG - 777-789 LID - 10.2147/IJN.S152400 [doi] AB - BACKGROUND: Titanium dioxide nanoparticles (TiO(2) NPs) have recently found applications in a wide variety of consumer goods. TiO(2) NPs exposure significantly increases fetal deformities and mortality. However, the potential toxicity of TiO(2) NPs on the growth and development of placenta has been rarely studied during mice pregnancy. PURPOSE: The objective of this study was to investigate the effects of maternal exposure of TiO(2) NPs on the placentation. METHODS: Mice were administered TiO(2) NPs by gavage at 0, 1 and 10 mg/kg/day from gestational day (GD) 1 to GD 13. Uteri and placentas from these mice were collected and counted the numbers of implanted and resorbed embryo and measured the placental weight on GD 13. Placental morphometry was observed by hematoxylin and eosin staining. The levels of Hand1, Esx1, Eomes, Hand2, Ascl2 and Fra1 mRNA were assessed by qRT-PCR. Uterine NK (uNK) cells were detected by using DBA lectin. Laminin immunohistochemical staining was to identify fetal vessels. Western blotting and transmission electron micrograph (TEM) were used to assess the apoptosis of placenta. RESULTS: No treatment-related difference was observed in the numbers of implanted and resorbed embryos and weight of placenta between the groups. However, 1 mg/kg/day TiO(2) NPs treatment significantly reduced the ratio of placenta/body weight on GD 13. The proportion of spongiotrophoblast in the 10 mg/kg/day dose group became higher than that in the control group, yet that of labyrinth was significantly lower in 10 mg/kg/day mice. The expression levels of Hand1, Esx1, Eomes, Hand2, Ascl2 and Fra1 mRNA markedly decreased in TiO(2) NP treated placentas. Furthermore, TiO(2) NPs treatment impaired the formation of intricate networks of fetal vessels and reduced the number of uNK cells, and inhibited proliferation and induced apoptosis of placenta by nuclear pyknosis, the activation of caspase-3 and upregulation of Bax protein and downregulation of Bcl-2 protein on GD 13. CONCLUSION: Gestational exposure to TiO(2) NPs significantly impairs the growth and development of placenta in mice, with a mechanism that seems to be involved in the dysregulation of vascularization, proliferation and apoptosis. Therefore, our results suggested the need for great caution while handling of the nanomaterials by workers and specially pregnant consumers. FAU - Zhang, Lu AU - Zhang L AD - Department of Physiology, Basic Medical College, Nanchang University, Nanchang. FAU - Xie, Xingxing AU - Xie X AD - Department of Physiology, Basic Medical College, Nanchang University, Nanchang. FAU - Zhou, Yigang AU - Zhou Y AD - Department of Color Ultrasonic Room, No 96716 Hospital of PLA. FAU - Yu, Dainan AU - Yu D AD - Department of Physiology, Basic Medical College, Nanchang University, Nanchang. FAU - Deng, Yu AU - Deng Y AD - Department of Physiology, Basic Medical College, Nanchang University, Nanchang. FAU - Ouyang, Jiexiu AU - Ouyang J AD - Jiangxi Provincial Key Laboratory of Reproductive Physiology and Pathology, Medical Experimental Teaching Center, Nanchang University, Nanchang, Jiangxi, People's Republic of China. FAU - Yang, Bei AU - Yang B AD - Department of Physiology, Basic Medical College, Nanchang University, Nanchang. FAU - Luo, Dan AU - Luo D AD - Department of Physiology, Basic Medical College, Nanchang University, Nanchang. FAU - Zhang, Dalei AU - Zhang D AD - Department of Physiology, Basic Medical College, Nanchang University, Nanchang. FAU - Kuang, Haibin AU - Kuang H AD - Department of Physiology, Basic Medical College, Nanchang University, Nanchang. AD - Jiangxi Provincial Key Laboratory of Reproductive Physiology and Pathology, Medical Experimental Teaching Center, Nanchang University, Nanchang, Jiangxi, People's Republic of China. LA - eng PT - Journal Article DEP - 20180205 PL - New Zealand TA - Int J Nanomedicine JT - International journal of nanomedicine JID - 101263847 RN - 0 (bcl-2-Associated X Protein) RN - 15FIX9V2JP (titanium dioxide) RN - D1JT611TNE (Titanium) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Caspase 3/metabolism MH - Cell Proliferation/drug effects MH - Female MH - Gene Expression Regulation, Developmental/drug effects MH - Maternal Exposure MH - Metal Nanoparticles/chemistry/*toxicity MH - Mice MH - Neovascularization, Pathologic/chemically induced MH - Organ Size/drug effects MH - Placenta/blood supply/*drug effects/metabolism MH - Placentation/*drug effects MH - Pregnancy MH - Titanium/chemistry/*toxicity MH - bcl-2-Associated X Protein/metabolism PMC - PMC5804269 OTO - NOTNLM OT - apoptosis OT - nanoparticles OT - placenta OT - proliferation OT - titanium dioxide OT - vascularization COIS- Disclosure The authors report no conflicts of interest in this work. EDAT- 2018/02/15 06:00 MHDA- 2018/04/26 06:00 PMCR- 2018/02/05 CRDT- 2018/02/15 06:00 PHST- 2018/02/15 06:00 [entrez] PHST- 2018/02/15 06:00 [pubmed] PHST- 2018/04/26 06:00 [medline] PHST- 2018/02/05 00:00 [pmc-release] AID - ijn-13-777 [pii] AID - 10.2147/IJN.S152400 [doi] PST - epublish SO - Int J Nanomedicine. 2018 Feb 5;13:777-789. doi: 10.2147/IJN.S152400. eCollection 2018.