Abstract
Oligo-astheno-teratozoospermia (OAT) is a global public health problem, which affects 30% men of childbearing age. Meanwhile, with the rapid development of industry and economy, the contents of rare earth elements (REEs) in the environment are increasing. However, little is known about the associations between REEs levels and OAT risk. To evaluate the associations between the levels of four REEs (samarium (Sm), hafnium (Hf), tungsten (W), rhenium (Re)) in seminal plasma and OAT risk, from October 2021 to November 2022, semen samples from 924 men of childbearing age (460 controls and 464 cases) were collected from the reproductive center of the First Affiliated Hospital of Anhui Medical University. Inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure the levels of Sm, Hf, Re and W in seminal plasma. Bayesian kernel machine regression (BKMR) was conducted to explore the joint effects of levels of four REEs in seminal plasma on the risk of OAT and select the one exerting a major role; generalized linear regression models (GLM) with log link function were employed to investigate the association of every REE level in seminal plasma and OAT risk; sankey diagram and linear regression models were utilized to describe the associations between the levels of four REEs and the indexes of sperm quality. The levels of four REEs in seminal plasma were higher in the case group than levels in the control group (pSm = 0.011, pHf = 0.040, pW = 0.062, pRe = 0.001, respectively). In BKMR analysis, the OAT risk increased when the overall levels of four REEs were higher than their 55th percentile compared to all of them at their 50th percentile, and Re level played a major role in the association. Additionally, Re level in seminal plasma was positively associated with the OAT risk in the single element model after adjustment of covariates (medium vs. low: OR (95% CI) = 1.55 (1.10, 2.18); high vs. low: OR (95% CI) = 1.69 (1.18, 2.42)). Lastly, the sankey diagram and linear regression models revealed that Sm level was negatively associated with the PR%, total sperm count and total progressively motile sperm count; Hf level was negatively associated with the PR%; W and Re levels were negatively associated with the PR% and total motility, and Re level was positively associated with abnormal morphology rate. Men of childbearing age with OAT had higher levels of Sm, Hf and Re in seminal plasma than those in the control group. An increasing trend for the OAT risk was observed with an increase in mixture levels of Sm, Hf, W and Re, and Re exposure level played a major role in the association whether in BKMR model or single element model. Additionally, the levels of these four REEs were negatively associated with the indexes of sperm quality.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Agarwal A, Mulgund A, Hamada A, Chyatte MR (2015) A unique view on male infertility around the globe. Reprod Biol Endocrinol 13:37. https://doi.org/10.1186/s12958-015-0032-1
Allan CM, Couse JF, Simanainen U, Spaliviero J, Jimenez M, Rodriguez K, Korach KS, Handelsman DJ (2010) Estradiol induction of spermatogenesis is mediated via an estrogen receptor-alpha mechanism involving neuroendocrine activation of follicle-stimulating hormone secretion. Endocrinology 151(6):2800–2810. https://doi.org/10.1210/en.2009-1477
Annapurna A, Jaya PG, Krishna KM, Ravi KC, Sivanarayana T, Madan K, Rama RG, Annapurna A (2015) Protective effect of alpha glucosyl hesperidin (g-hesperidin) on chronic vanadium induced testicular toxicity and sperm nuclear dna damage in male sprague dawley rats. Andrologia 47(5):568–578. https://doi.org/10.1111/and.12304
Arzuaga X, Smith MT, Gibbons CF, Skakkebaek NE, Yost EE, Beverly B, Hotchkiss AK, Hauser R, Pagani RL, Schrader SM, Zeise L, Prins GS (2019) Proposed key characteristics of male reproductive toxicants as an approach for organizing and evaluating mechanistic evidence in human health hazard assessments. Environ Health Perspect 127(6):65001. https://doi.org/10.1289/EHP5045
Balaram V (2019) Rare earth elements:A review of applications, occurrence, exploration, analysis, recycling, and environmental impact. Geosci Front 10(4):1285–1303. https://doi.org/10.1016/j.gsf.2018.12.005
Chandra AK, Ghosh R, Chatterjee A, Sarkar M (2007) Vanadium-induced testicular toxicity and its prevention by oral supplementation of zinc sulphate. Toxicol Mech Methods 17(4):175–187. https://doi.org/10.1080/15376510601185871
Chen J, Xiao H, Qi T, Chen D, Long H, Liu S (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(3):2076–2086. https://doi.org/10.1007/s11356-014-3499-y
Cocuzza M, Alvarenga C, Pagani R (2013) The epidemiology and etiology of azoospermia. Clinics (Sao Paulo) 68:15–26. https://doi.org/10.6061/clinics/2013(Sup01)03
Cortizo AM, Bruzzone L, Molinuevo S, Etcheverry SB (2000) A possible role of oxidative stress in the vanadium-induced cytotoxicity in the mc3t3e1 osteoblast and umr106 osteosarcoma cell lines. Toxicology 147(2):89–99. https://doi.org/10.1016/S0300-483X(00)00181-5
Dehghani GA, Ahmadi S, Omrani GR (1997) Effects of vanadyl sulphate on glucose homeostasis in severe diabetes induced by streptozotocin in rats. Indian J Med Res 106:481–485
Fortoul T, Bizarronevares P, Acevedonava S, Pinonzarate G, Rodriguezlara V, Colinbarenque L, Mussaligalante P, Avilacasado M, Avilacosta M, Saldivarosorio L (2007) Ultrastructural findings in murine seminiferous tubules as a consequence of subchronic vanadium pentoxide inhalation. Reprod Toxicol 23(4):588–592. https://doi.org/10.1016/j.reprotox.2007.03.004
Friel JK, Andrews WL, Jackson SE, Longerich HP, Mercer C, Mcdonald A, Dawson B, Sutradhar B (1999) Elemental composition of human milk from mothers of premature and full-term infants during the first 3 months of lactation. Biol Trace Elem Res 67(3):225–247. https://doi.org/10.1007/BF02784423
Hosseini SH, Sadighi GM, Meybodi AM, Sabbaghian M (2017) The impact of rabl2b gene (rs144944885) on human male infertility in patients with oligoasthenoteratozoospermia and immotile short tail sperm defects. J Assist Reprod Genet 34(4):505–510. https://doi.org/10.1007/s10815-016-0863-5
Hu P, Vinturache A, Li H, Tian Y, Yuan L, Cai C, Lu M, Zhao J, Zhang Q, Gao Y, Liu Z, Ding G (2020) Urinary organophosphate metabolite concentrations and pregnancy outcomes among women conceiving throughin vitro fertilization in shanghai, china. Environ Health Perspect 128(9):97007. https://doi.org/10.1289/EHP7076
Ingram JL, Rice AB, Santos J, Van Houten B, Bonner JC (2003) Vanadium-induced hb-egf expression in human lung fibroblasts is oxidant dependent and requires map kinases. Am J Physiol Lung Cell Mol Physiol 284(5):L774–L782. https://doi.org/10.1152/ajplung.00189.2002
Inouye LS, Jones RP, Bednar AJ (2006) Tungsten effects on survival, growth, and reproduction in the earthworm, eisenia fetida. Environ Toxicol Chem 25(3):763–768. https://doi.org/10.1897/04-578r.1
Jamil S, Shoaib M, Aziz W, Ather MH (2020) Does male factor infertility impact on self-esteem and sexual relationship? Andrologia 52(2):e13460. https://doi.org/10.1111/and.13460
Kamboj VP, Kar AB (1964) Antitesticular effect of metallic and rare earth salts. J Reprod Fertil 7:21–28. https://doi.org/10.1530/jrf.0.0070021
Lee KH, Chen HP, Leung CM, Chen HL, Tsai SS, Hsu PC (2015) Effects of indium chloride exposure on sperm morphology and DNA integrity in rats. J Food Drug Anal 23(1):152–160. https://doi.org/10.1016/j.jfda.2014.10.001
Levack VM, Hone PA, Phipps AW, Harrison JD (2002) The placental transfer of cerium: experimental studies and estimates of doses to the human fetus from super(141)ce and super(144)ce. Int J Radiat Biol 78(3):227–235. https://doi.org/10.1080/0955300011009722
Levine H, Jorgensen N, Martino-Andrade A, Mendiola J, Weksler-Derri D, Mindlis I, Pinotti R, Swan SH (2017) Temporal trends in sperm count: a systematic review and meta-regression analysis. Hum Reprod Update 23(6):646–659. https://doi.org/10.1093/humupd/dmx022
Liu D, Wang X, Chen Z (2012) Effects of rare earth elements and ree-binding proteins on physiological responses in plants. Protein Pept Lett 19(2):198–202. https://doi.org/10.2174/092986612799080121
Martino C, Chianese T, Chiarelli R, Roccheri MC, Scudiero R (2022) Toxicological impact of rare earth elements (rees) on the reproduction and development of aquatic organisms using sea urchins as biological models. Int J Mol Sci 23(5):2876. https://doi.org/10.3390/ijms23052876
Marzec-Wroblewska U, Kaminski P, Lakota P, Ludwikowski G, Szymanski M, Wasilow K, Stuczynski T, Bucinski A, Jerzak L (2015) Determination of rare earth elements in human sperm and association with semen quality. Arch Environ Contam Toxicol 69(2):191–201. https://doi.org/10.1007/s00244-015-0143-x
Mcinturf SM, Bekkedal MY, Wilfong E, Arfsten D, Chapman G, Gunasekar PG (2011) The potential reproductive, neurobehavioral and systemic effects of soluble sodium tungstate exposure in sprague-dawley rats. Toxicol Appl Pharmacol 254(2):133–137. https://doi.org/10.1016/j.taap.2010.04.021
Meng J, Holdcraft RW, Shima JE, Griswold MD, Braun RE (2005) Androgens regulate the permeability of the blood-testis barrier. Proc Natl Acad Sci USA 102(46):16696–16700. https://doi.org/10.1073/pnas.0506084102
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(2):194–198. https://doi.org/10.1016/j.chemosphere.2010.06.057
Peng RL, Pan XC, 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(1):20–22
Pizent A, Tariba B, Zivkovic T (2012) Reproductive toxicity of metals in men. Arh Hig Rada Toksikol 63(Suppl 1):35–46. https://doi.org/10.2478/10004-1254-63-2012-2151
Ramlau-Hansen CH, Thulstrup AM, Aggerholm AS, Jensen MS, Toft G, Bonde JP (2007) Is smoking a risk factor for decreased semen quality? A cross-sectional analysis. Hum Reprod 22(1):188–196. https://doi.org/10.1093/humrep/del364
Shrivastava S, Jadon A, Shukla S, Mathur R (2007) Chelation therapy and vanadium: effect on reproductive organs in rats. Indian J Exp Biol 45(6):515–523
Skakkebaek NE, Rajpert-De Meyts E, Buck Louis GM, Toppari J, Andersson A, Eisenberg ML, Jensen TK, Jørgensen N, Swan SH, Sapra KJ, Ziebe S, Priskorn L, Juul A (2016) Male reproductive disorders and fertility trends: influences of environment and genetic susceptibility. Physiol Rev 96(1):55–97. https://doi.org/10.1152/physrev.00017.2015
Stone BA, Alex A, Werlin LB, Marrs RP (2013) Age thresholds for changes in semen parameters in men. Fertil Steril 100(4):952–958. https://doi.org/10.1016/j.fertnstert.2013.05.046
Taylor DM, Seidel A, Doerfel H (1985) The metabolism of radiohafnium in marmosets and hamsters. Int J Nuclear Med Biol 12(5):387–391. https://doi.org/10.1016/S0047-0740(85)80009-7
Tong SL, Zhu WZ, Gao ZH, Meng YX, Peng RL, Lu GC (2004) Distribution characteristics of rare earth elements in children's scalp hair from a rare earths mining area in southern china. J Environ Sci Health a Tox Hazard Subst Environ Eng 39(9):2517–2532. https://doi.org/10.1081/ese-200026332
Uccelli L, Martini P, Cittanti C, Carnevale A, Missiroli L, Giganti M, Bartolomei M, Boschi A (2019) Therapeutic radiometals: worldwide scientific literature trend analysis (2008(-)2018). Molecules 24:(3). https://doi.org/10.3390/molecules24030640
Uccelli L, Boschi A, Cittanti C, Martini P, Panareo S, Tonini E, Nieri A, Urso L, Caracciolo M, Lodi L, Carnevale A, Giganti M, Bartolomei M (2021) 90y/177lu-dotatoc: from preclinical studies to application in humans. Pharmaceutics 13(9):1463. https://doi.org/10.3390/pharmaceutics13091463
Vander Borght M, Wyns C (2018) Fertility and infertility: definition and epidemiology. Clin Biochem 62:2–10. https://doi.org/10.1016/j.clinbiochem.2018.03.012
Wang Y, Sun Y, Huang Z, Wang P, Feng W, Li J, Yang P, Wang M, Sun L, Chen Y, Liu C, Yue J, Gu L, Zeng Q, Lu W (2016) Associations of urinary metal levels with serum hormones, spermatozoa apoptosis and sperm dna damage in a chinese population. Environ Int 94:177–188. https://doi.org/10.1016/j.envint.2016.05.022
Wang Y, Chen H, Li X, Chen Y, Liu C, Feng W, Zeng Q, Wang P, Pan A, Lu W (2018) Concentrations of vanadium in urine and seminal plasma in relation to semen quality parameters, spermatozoa dna damage and serum hormone levels. Sci Total Environ 645:441–448. https://doi.org/10.1016/j.scitotenv.2018.07.137
Witten ML, Sheppard PR, Witten BL (2012) Tungsten toxicity. Chem Biol Interact 196(3):87–88. https://doi.org/10.1016/j.cbi.2011.12.002
Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, Rienzi L, Sunde A, Schmidt L, Cooke ID, Simpson JL, van der Poel S (2017) The international glossary on infertility and fertility care, 2017. Fertil Steril 108(3):393–406. https://doi.org/10.1016/j.fertnstert.2017.06.005
Zhang DY, Shen XY, Ruan Q, Xu XL, Yang SP, Lu Y, Xu HY, Hao FL (2014) Effects of subchronic samarium exposure on the histopathological structure and apoptosis regulation in mouse testis. Environ Toxicol Pharmacol 37(2):505–512. https://doi.org/10.1016/j.etap.2014.01.007
Zhang DY, Shen XY, Xu XL, Ruan Q, Hu SS, Chen YY, Wang ZM (2016) Effect of acute/subchronic samarium exposure on the concentration, motility, and morphology of sperm in male mice. Genet Mol Res 15(2). https://doi.org/10.4238/gmr.15028807
Zhou J, Guo L, Xiao W, Geng Y, Wang X, Shi X, Dan S (2012) physiological effects of rare earth elements and their application in traditional chinese medicine. Zhongguo Zhong Yao Za Zhi 37(15):2238–2241
Acknowledgement
The authors would like to thank the Experimental Center of Preventive Medicine, School of Public Health, Anhui Medical University for providing instrument support. We would also like to thank the Reproductive Center of the First Affiliated Hospital of Anhui Medical University for participant inclusion and sample collection support.
Funding sources
This work was supported by the National Natural Science Foundation of China (NSFC-82173532, NSFC-81971455), the National Key Research and Development Program (2018YFC1004201, 2016YFC1000204), the Postdoctoral Research Foundation of China (2021M700181), the Research Fund of Anhui Institute of translational medicine (2022zhyx-C16), the Excellent Young Talents Fund Program of Higher Education Institutions of Anhui Province (gxyq2021173), the Postgraduate Research and Practice Innovation Project of Anhui Medical University (YJS20230076) and the Anhui Medical University "Clinical Early Contact Research" Training Program Project (2022-ZQKY-174, 2022-ZQKY-48).
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Tingting Jiang: Conceptualization, Investigation, Writing - original draft. Shitao He: Investigation, Writing - original draft. Jieyu Wang: Investigation, Validation. Mengzhu Li: Investigation, Validation. Jiayi Chen: Investigation, Writing - original draft. Dongyang Zhang: Investigation, Validation. Runtao Zhang: Data curation, Review. Fangbiao Tao: Conceptualization, Writing - review & editing. Yuyou Yao: Conceptualization, Visualization, Writing - review & editing. Jiahu Hao: Conceptualization, Visualization, Project administration. Dongmei Ji: Conceptualization, Visualization, Project administration, Funding acquisition. Chunmei Liang: Conceptualization, Visualization, Writing - review & editing, Project administration, Funding acquisition.
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Highlights
• BKMR model showed a positive correlation between the REEs levels and the risk of OAT
• Higher REEs levels were positively associated with the risk of OAT
• Sankey diagram showed that levels of REEs were negatively associated with sperm quality
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Jiang, ., He, S., Wang, J. et al. The association between levels of samarium, hafnium, tungsten and rhenium in seminal plasma and the risk of idiopathic oligo-astheno-teratozoospermia in men of childbearing age. Environ Sci Pollut Res 31, 668–681 (2024). https://doi.org/10.1007/s11356-023-31017-2
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DOI: https://doi.org/10.1007/s11356-023-31017-2