PMID- 37652228 OWN - NLM STAT- MEDLINE DCOM- 20231026 LR - 20231112 IS - 1873-6424 (Electronic) IS - 0269-7491 (Linking) VI - 337 DP - 2023 Nov 15 TI - Metabolomics insights into the effects of pre-pregnancy lead exposure on bone metabolism in pregnant rats. PG - 122468 LID - S0269-7491(23)01470-7 [pii] LID - 10.1016/j.envpol.2023.122468 [doi] AB - Today's women of childbearing age with a history of high lead (Pb) exposure in childhood have large Pb body burdens, which increases Pb release during pregnancy by promoting bone Pb mobilisation. The purpose of this study was to investigate the metabolic mechanisms underlying bone Pb mobilisation and explore the bone metabolism-related pathways during pregnancy. Drinking water containing 0.05% sodium acetate or Pb acetate was provided to weaned female rats for 4 weeks followed by a 4-week washout period, and then rats were co-caged with healthy males of the same age until pregnancy. Blood and bone tissues of the female rats were collected at gestational day (GD) 3 (early pregnancy), GD 10 (middle pregnancy), and GD 17 (late pregnancy), respectively. Pb and calcium concentrations, biomarkers for bone turnover, bone microstructure, serum metabolomics, and metabolic indicators were intensively analyzed. The results demonstrated that pre-pregnancy Pb exposure elevated blood lead levels (BLLs) at GD17, accompanied by a negative correlation between BLLs and trabecular bone Pb levels. Meanwhile, Pb-exposed rats had low bone mass and aberrant bone architecture with a larger number of mature osteoclasts (OCs) compared to the control group. Moreover, the metabolomics uncovered that Pb exposure caused mitochondrial dysfunction, such as enhanced oxidative stress and inflammatory response, and suppressed energy metabolism. Additionally, the levels of ROS, MDA, IL-1beta, and IL-18 involved in redox and inflammatory pathways of bone tissues were significantly increased in the Pb-exposed group, while antioxidant SOD and energy metabolism-related indicators including ATP levels, Na(+)-K(+)-ATPase, and Ca(2+)-Mg(2+)-ATPase activities were significantly decreased. In conclusion, pre-pregnancy Pb exposure promotes bone Pb mobilisation and affects bone microstructure in the third trimester of pregnancy, which may be attributed to OC activation and mitochondrial dysfunction. CI - Copyright (c) 2023 Elsevier Ltd. All rights reserved. FAU - Zhang, Lin AU - Zhang L AD - MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. FAU - Lin, Yin AU - Lin Y AD - MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. FAU - Lu, An-Xin AU - Lu AX AD - MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. FAU - Liu, Jun-Xia AU - Liu JX AD - MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. FAU - Li, Jing AU - Li J AD - School of Public Health, Shanghai Jiao Tong University, Shanghai, 200025, China. FAU - Yan, Chong-Huai AU - Yan CH AD - MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. Electronic address: yanchk@qq.com. LA - eng PT - Journal Article DEP - 20230829 PL - England TA - Environ Pollut JT - Environmental pollution (Barking, Essex : 1987) JID - 8804476 RN - 2P299V784P (Lead) RN - 0 (Antioxidants) RN - SY7Q814VUP (Calcium) RN - EC 3.6.1.- (Adenosine Triphosphatases) SB - IM MH - Male MH - Rats MH - Animals MH - Humans MH - Female MH - Pregnancy MH - *Lead MH - *Antioxidants/metabolism MH - Oxidative Stress MH - Calcium/metabolism MH - Adenosine Triphosphatases/metabolism OTO - NOTNLM OT - Bone Pb mobilisation OT - Metabolomics OT - Mitochondrial dysfunction OT - Osteoclast OT - Pregnancy OT - Trabecular bone COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/09/01 00:41 MHDA- 2023/10/26 06:42 CRDT- 2023/08/31 19:26 PHST- 2023/05/29 00:00 [received] PHST- 2023/08/07 00:00 [revised] PHST- 2023/08/25 00:00 [accepted] PHST- 2023/10/26 06:42 [medline] PHST- 2023/09/01 00:41 [pubmed] PHST- 2023/08/31 19:26 [entrez] AID - S0269-7491(23)01470-7 [pii] AID - 10.1016/j.envpol.2023.122468 [doi] PST - ppublish SO - Environ Pollut. 2023 Nov 15;337:122468. doi: 10.1016/j.envpol.2023.122468. Epub 2023 Aug 29.