Abstract
Telomere length (TL) is considered a marker of biological aging and lifetime health, and some epidemiological studies report that the environmental exposures may influence TL at birth. We aimed to investigate the associations between prenatal rare earth elements (REE) exposure and newborn TL. A total of 587 mother-newborn pairs were recruited during 2013 to 2015 in Wuhan, China. Maternal urinary concentrations of REE collected during three trimesters were measured by inductively coupled plasma mass spectrometry. Quantitative real-time polymerase chain reaction was used to measure relative cord blood TL. The trimester-specific associations between prenatal REE exposure and cord blood TL were evaluated using multiple informant models. Weighted quantile sum regression was used to estimate the mixture effect of urinary REE on cord blood TL. After adjustment for potential confounders, per doubling of urinary REE (Dy, Yb, Pr, Nd, and Tm) concentrations (μg/g creatinine) during the second trimester was respectively associated with 1.94% (95% CI 0.19%, 3.72%), 2.10% (95% CI 0.31%, 3.92%), 2.11% (95% CI 0.35%, 3.89%), 2.08% (95% CI 0.01%, 4.20%), and 1.38% (95% CI 0.09%, 2.70%) increase in cord blood TL. Furthermore, exposure to the mixture of REE during the second trimester was also significantly associated with increased cord blood TL (percent change 1.20%, 95% CI 0.30%, 2.11%). However, these associations were not statistically significant in the first and third trimesters. This study provides new evidence on the potential effect of prenatal REE exposure on the initial (newborn) setting of offspring’s telomere biology. Further epidemiological studies are warranted to confirm our findings.
Similar content being viewed by others
Data availability
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
References
Abduljalil K, Furness P, Johnson TN, Rostami-Hodjegan A, Soltani H (2012) Anatomical, physiological and metabolic changes with gestational age during normal pregnancy: a database for parameters required in physiologically based pharmacokinetic modelling. Clin Pharmacokinet 51:365–396. https://doi.org/10.2165/11597440-000000000-00000
Akbar AN, Vukmanovic-Stejic M (2007) Telomerase in T lymphocytes: use it and lose it? J Immunol 178:6689–6694. https://doi.org/10.4049/jimmunol.178.11.6689
Akiyama M, Hideshima T, Hayashi T, Tai YT, Mitsiades CS, Mitsiades N et al (2002) Cytokines modulate telomerase activity in a human multiple myeloma cell line. Cancer Res 62:3876–3882
Bao TM, Tian Y, Wang LX, Wu T, Lu LN, Ma HY et al (2018) An investigation of lanthanum and other metals levels in blood, urine and hair among residents in the rare earth mining area of a city in China. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 36:99–101. https://doi.org/10.3760/cma.j.issn.1001-9391.2018.02.005
Bettinelli M, Spezia S, Terni C, Ronchi A, Balducci C, Minoia C (2002) Determination of rare earth elements in urine by electrothermal vaporization inductively coupled plasma mass spectrometry. Rapid Commun Mass Spectrom 16:579–584. https://doi.org/10.1002/rcm.609
Blackburn EH (2001) Switching and signaling at the telomere. Cell 106:661–673. https://doi.org/10.1016/S0092-8674(01)00492-5
Blackburn EH (2005) Telomeres and telomerase: their mechanisms of action and the effects of altering their functions. Febs Lett 579:859–862. https://doi.org/10.1016/j.febslet.2004.11.036
Blackburn EH, Epel ES, Lin J (2015) Human telomere biology: a contributory and interactive factor in aging, disease risks, and protection. Science 350:1193–1198. https://doi.org/10.1126/science.aab3389
Carrico C, Gennings C, Wheeler DC, Factor-Litvak P (2015) Characterization of weighted quantile sum regression for highly correlated data in a risk analysis setting. J Agric Biol Environ Stat 20:100–120. https://doi.org/10.1007/s13253-014-0180-3
Chen J, Xiao HJ, Qi T, Chen DL, Long HM, Liu SH (2015) Rare earths exposure and male infertility: the injury mechanism study of rare earths on male mice and human sperm. Environ Sci Pollut Res Int 22:2076–2086. https://doi.org/10.1007/s11356-014-3499-y
Cheng J, Fei M, Fei M, Sang X, Sang X, Cheng Z et al (2014) Gene expression profile in chronic mouse liver injury caused by long-term exposure to CeCl3. Environ Toxicol 29:837–846. https://doi.org/10.1002/tox.21826
Cowell W, Colicino E, Tanner E, Amarasiriwardena C, Andra SS, Bollati V et al (2020) Prenatal toxic metal mixture exposure and newborn telomere length: modification by maternal antioxidant intake. Environ Res 190:110009. https://doi.org/10.1016/j.envres.2020.110009
Dutta T, Kim KH, Uchimiya M, Kwon EE, Jeon BH, Deep A et al (2016) Global demand for rare earth resources and strategies for green mining. Environ Res 150:182–190. https://doi.org/10.1016/j.envres.2016.05.052
Entringer S, de Punder K, Buss C, Wadhwa PD (2018) The fetal programming of telomere biology hypothesis: an update. Philos Trans R Soc Lond B Biol Sci 373https://doi.org/10.1098/rstb.2017.0151
Fairlie J, Holland R, Pilkington JG, Pemberton JM, Harrington L, Nussey DH (2016) Lifelong leukocyte telomere dynamics and survival in a free-living mammal. Aging Cell 15:140–148. https://doi.org/10.1111/acel.12417
Fan G, Zheng H, Liu Y, Yuan Z (2003) Study on relation between exposure to rare earth elements and physical growth and development of children. Chin J Public Health 19:1283–1284 ((In Chinese))
Fan G, Zheng H, Yuan Z. 2005. Effects of thulium exposure on IQ of children. J Environ Health 22:256–257. https://doi.org/10.16241/j.cnki.1001-5914.2005.04.008
Fei M, Li N, Ze Y, Liu J, Wang S, Gong X et al (2011) The mechanism of liver injury in mice caused by lanthanoids. Biol Trace Elem Res 140:317–329. https://doi.org/10.1007/s12011-010-8698-x
Genyuan J, Hongping Z, Qiuling L, Haodong X (2018) Current status of rare earth resources in China and strategies for its sustainable development. China Mining Magzine 27:9–16 ((In Chinese))
Hao Z, Li Y, Li H, Wei B, Liao X, Liang T et al (2015) Levels of rare earth elements, heavy metals and uranium in a population living in Baiyun Obo, Inner Mongolia, China: a pilot study. Chemosphere 128:161–170. https://doi.org/10.1016/j.chemosphere.2015.01.057
Haque N, Hughes A, Lim S, Vernon C (2014) Rare earth elements: overview of mining, mineralogy, uses, sustainability and environmental impact. Resources 3:614–635. https://doi.org/10.3390/resources3040614
Haycock PC, Burgess S, Nounu A, Zheng J, Okoli GN, Bowden J et al (2017) Association between telomere length and risk of cancer and non-neoplastic diseases a Mendelian randomization study. Jama Oncol 3:636–651. https://doi.org/10.1001/jamaoncol.2016.5945
Heidinger BJ, Blount JD, Boner W, Griffiths K, Metcalfe NB, Monaghan P (2012) Telomere length in early life predicts lifespan. Proc Natl Acad Sci U S A 109:1743–1748. https://doi.org/10.1073/pnas.1113306109
Herlin M, Broberg K, Igra AM, Li H, Harari F, Vahter M (2019) Exploring telomere length in mother-newborn pairs in relation to exposure to multiple toxic metals and potential modifying effects by nutritional factors. BMC Med 17:77. https://doi.org/10.1186/s12916-019-1309-6
Hjelmborg JB, Dalgard C, Moller S, Steenstrup T, Kimura M, Christensen K et al (2015) The heritability of leucocyte telomere length dynamics. J Med Genet 52:297–302. https://doi.org/10.1136/jmedgenet-2014-102736
Hodes RJ, Hathcock KS, Weng NP (2002) Telomeres in t and b cells. Nat Rev Immunol 2:699–706. https://doi.org/10.1038/nri890
Hou L, Wang S, Dou C, Zhang X, Yu Y, Zheng Y et al (2012) Air pollution exposure and telomere length in highly exposed subjects in Beijing, China: a repeated-measure study. Environ Int 48:71–77. https://doi.org/10.1016/j.envint.2012.06.020
Karimi B, Nodehi RN, Yunesian M (2020) Serum level of PCBs and OCPs and leukocyte telomere length among adults in Tehran, Iran. Chemosphere 248https://doi.org/10.1016/j.chemosphere.2020.126092
Kitamura Y, Usuda K, Shimizu H, Fujimoto K, Kono R, Fujita A et al (2012) Urinary monitoring of exposure to yttrium, scandium, and europium in male Wistar rats. Biol Trace Elem Res 150:322–327. https://doi.org/10.1007/s12011-012-9494-6
Leggett R, Ansoborlo E, Bailey M, Gregoratto D, Paquet F, Taylor D (2014) Biokinetic data and models for occupational intake of lanthanoids. Int J Radiat Biol 90:996–1010. https://doi.org/10.3109/09553002.2014.887868
Li HQ, Engstrom K, Vahter M, Broberg K (2012) Arsenic exposure through drinking water is associated with longer telomeres in peripheral blood. Chem Res Toxicol 25:2333–2339. https://doi.org/10.1021/tx300222t
Li Z, Shulei L, Hui C, Kexin H, Yuxiu N (2004) Effects of mixed rare earth changle on DNA damage of embryo cell of pregnancy rat. J Chinese Rare Earth Soc 22:390–392 ((In Chinese))
Lin J, Cheon J, Brown R, Coccia M, Puterman E, Aschbacher K et al (2016) Systematic and cell type-specific telomere length changes in subsets of lymphocytes. J Immunol Res 2016:5371050. https://doi.org/10.1155/2016/5371050
Liu H, Chen Q, Lei L, Zhou W, Huang L, Zhang J et al (2018) Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances affects leukocyte telomere length in female newborns. Environ Pollut 235:446–452. https://doi.org/10.1016/j.envpol.2017.12.095
Liu L, Bailey SM, Okuka M, Munoz P, Li C, Zhou L et al (2007) Telomere lengthening early in development. Nat Cell Biol 9:1436–1441. https://doi.org/10.1038/ncb1664
Liu L, Wang L, Ni W, Pan Y, Chen Y, Xie Q et al (2021) Rare earth elements in umbilical cord and risk for orofacial clefts. Ecotoxicol Environ Saf 207:111284. https://doi.org/10.1016/j.ecoenv.2020.111284
Liu Y, Wu M, Zhang L, Bi J, Song L, Wang L et al (2019) Prenatal exposure of rare earth elements cerium and ytterbium and neonatal thyroid stimulating hormone levels: findings from a birth cohort study. Environ Int 133:105222. https://doi.org/10.1016/j.envint.2019.105222
Liu Y, Wu M, Song L, Bi J, Wang L, Chen K, et al. (2020) Association between prenatal rare earth elements exposure and premature rupture of membranes: results from a birth cohort study. Environ Res:110534. https://doi.org/10.1016/j.envres.2020.110534
Martens DS, Cox B, Janssen BG, Clemente DBP, Gasparrini A, Vanpoucke C et al (2017) Prenatal air pollution and newborns’ predisposition to accelerated biological aging. JAMA Pediatr 171:1160–1167. https://doi.org/10.1001/jamapediatrics.2017.3024
Mitro SD, Birnbaum LS, Needham BL, Zota AR (2016) Cross-sectional associations between exposure to persistent organic pollutants and leukocyte telomere length among U.S. adults in NHANES, 2001–2002. Environ Health Perspect 124:651–658. https://doi.org/10.1289/ehp.1510187
Oral R, Bustamante P, Warnau M, D’Ambra A, Guida M, Pagano G (2010) Cytogenetic and developmental toxicity of cerium and lanthanum to sea urchin embryos. Chemosphere 81:194–198. https://doi.org/10.1016/j.chemosphere.2010.06.057
Pagano G, Guida M, Tommasi F, Oral R (2015) Health effects and toxicity mechanisms of rare earth elements-knowledge gaps and research prospects. Ecotoxicol Environ Saf 115:40–48. https://doi.org/10.1016/j.ecoenv.2015.01.030
Peng R, Pan X, Xie Q (2003) Relationship of the hair content of rare earth elements in young children aged 0 to 3 years to that in their mothers living in a rare earth mining area of Jiangxi. Zhonghua Yu Fang Yi Xue Za Zhi 37:20–22 ((In Chinese))
Pieters N, Janssen BG, Dewitte H, Cox B, Cuypers A, Lefebvre W et al (2016) Biomolecular markers within the core axis of aging and particulate air pollution exposure in the elderly: a cross-sectional study. Environ Health Perspect 124:943–950. https://doi.org/10.1289/ehp.1509728
Ray JG, Vermeulen MJ, Bharatha A, Montanera WJ, Park AL (2016) Association between MRI exposure during pregnancy and fetal and childhood outcomes. JAMA 316:952–961. https://doi.org/10.1001/jama.2016.12126
Rosa MJ, Hsu HHL, Just AC, Brennan KJ, Bloomquist T, Kloog I et al (2019) Association between prenatal particulate air pollution exposure and telomere length in cord blood: effect modification by fetal sex. Environ Res 172:495–501. https://doi.org/10.1016/j.envres.2019.03.003
Rosner B (2011) Fundamentals of biostatistics. Brooks/Cole, Boston, MA
Sanchez BN, Hu H, Litman HJ, Tellez-Rojo MM (2011) Statistical methods to study timing of vulnerability with sparsely sampled data on environmental toxicants. Environ Health Perspect 119:409–415. https://doi.org/10.1289/ehp.1002453
Schaetzlein S, Lucas-Hahn A, Lemme E, Kues WA, Dorsch M, Manns MP et al (2004) Telomere length is reset during early mammalian embryogenesis. P Natl Acad Sci USA 101:8034–8038. https://doi.org/10.1073/pnas.0402400101
Song L, Liu B, Zhang L, Wu M, Wang L, Cao Z et al (2019a) Association of prenatal exposure to arsenic with newborn telomere length: results from a birth cohort study. Environ Res 175:442–448. https://doi.org/10.1016/j.envres.2019.05.042
Song L, Zhang B, Liu B, Wu M, Zhang L, Wang L et al (2019b) Effects of maternal exposure to ambient air pollution on newborn telomere length. Environ Int 128:254–260. https://doi.org/10.1016/j.envint.2019.04.064
Song LL, Liu BQ, Wu MY, Zhang LN, Wang LL, Zhang B, et al. (2019c) Prenatal exposure to phthalates and newborn telomere length: a birth cohort study in Wuhan, China. Environ Health Perspect 127https://doi.org/10.1289/Ehp4492
Taylor DM, Leggett RW (2003) A generic biokinetic model for predicting the behaviour of the lanthanide elements in the human body. Radiat Protect Dosim 105:193–198. https://doi.org/10.1093/oxfordjournals.rpd.a006222
Wang B, Yan LL, Huo WH, Lu Q, Cheng ZX, Zhang JX et al (2017) Rare earth elements and hypertension risk among housewives: a pilot study in Shanxi Province China. Environ Pollut 220:837–842. https://doi.org/10.1016/j.envpol.2016.10.066
Wei J, Wang C, Yin S, Pi X, Jin L, Li Z et al (2020) Concentrations of rare earth elements in maternal serum during pregnancy and risk for fetal neural tube defects. Environ Int 137:105542. https://doi.org/10.1016/j.envint.2020.105542
Wei Z, Aiguo R, Zi Y, Lijun P, Ling H, Qing X et al (2005) Correlation studies of trace elements in mother’s hair, venous blood and cord blood. Chin J Repro Health 16:209–212. https://doi.org/10.3969/j.issn.1671-878X.2005.04.020
Wu YX, Liu YM, Ni N, Bao B, Zhang C, Lu LG (2012) High lead exposure is associated with telomere length shortening in Chinese battery manufacturing plant workers. Occup Environ Med 69:557–563. https://doi.org/10.1136/oemed-2011-100478
Zhang LN, Song LL, Liu BQ, Wu MY, Wang LL, Zhang B et al (2019) Prenatal cadmium exposure is associated with shorter leukocyte telomere length in Chinese newborns. BMC Med 17:27. https://doi.org/10.1186/s12916-019-1262-4
Zota AR, Needham BL, Blackburn EH, Lin J, Park SK, Rehkopf DH et al (2015) Associations of cadmium and lead exposure with leukocyte telomere length: findings from National Health and Nutrition Examination Survey, 1999–2002. Am J Epidemiol 181:127–136. https://doi.org/10.1093/aje/kwu293
Acknowledgements
We thank all the study participants in this study and the staffs of the Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital).
Funding
This study was funded by the National Natural Science Foundation of China (82073660, 82003479) and the China Postdoctoral Science Foundation (2019M662646, 2020T130220).
Author information
Authors and Affiliations
Contributions
YJW, SQX, and LLS conceived the protocol. MYW, JNB, LLW, QL, CX, and ZQC contributed to data collection. YYL, MYW, and LLS contributed to analysis and interpretation of data. YYL wrote the original draft. YJW reviewed and edited the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
The study protocol was approved by the ethics committee of the Tongji Medical College, Huazhong University of Science and Technology (No. S152), and the Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital) (No. 2016003). Individual written informed consent was obtained from all participating mothers at enrollment.
Consent for publication
The current manuscript does not contain any individual person’s data in any form (including any individual details, images, or videos).
Competing interests
The authors declare no competing interests.
Additional information
Responsible Editor: Lotfi Aleya.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Liu, Y., Song, L., Wu, M. et al. Association between rare earth element exposure during pregnancy and newborn telomere length. Environ Sci Pollut Res 30, 38751–38760 (2023). https://doi.org/10.1007/s11356-022-24958-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-022-24958-7