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Effects of perinatal exposure to endocrine-disrupting chemicals on the reproductive system of F3 generation male rodents: a meta-analysis

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Abstract

To explore the relationship between perinatal exposure to endocrine-disrupting chemicals and the male reproductive system of F3 generation, and to evaluate the toxicological effects of endocrine-disrupting chemicals on the reproductive system of F3 generation male rodents. PubMed and Web of Science databases were searched to obtain the studies; overall risk ratios (RRs) with 95% confidence intervals (95% CIs) were used to evaluate the relationship between exposure to endocrine-disrupting chemicals and reproductive system damage in F3 generation male rodents. Nine studies were included for analysis. Endocrine-disrupting chemicals are significantly associated with the reproductive system of male rodents of F3 generation, especially the testis (RR = 3.13, 95% CI: 2.05, 4.76), prostate (RR = 2.26, 95% CI: 1.27, 4.00), and kidney (RR = 2.83, 95% CI: 1.77, 4.52), but the current analysis does not prove that EDCs are the adverse factors for puberty abnormalities. The results indicated that the overall associations between atrazine (RR = 3.06, 95% CI: 1.10, 8.51, P = 0.032), DDT (RR = 6.26, 95% CI: 1.56, 25.08, P = 0.010), pesticide and insect repellent mixture (permethrin and DEET) (RR = 2.23, 95% CI: 1.34, 3.69, P = 0.002), and vinclozolin (RR = 4.71, 95% CI: 2.74, 8.10, P = 0.000) and reproductive system damage in F3 generation male rodents were statistically significant. Our study indicated that EDCs have an atavistic effect on the male reproductive system, and we should pay attention to the long-term effects of environmental exposure to endocrine disruptors in future generations.

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Data availability

All data generated and analyzed during this study are included in this published article (and its supplementary information files).

References

  • Abdel-Rahman A, Shetty AK, Abou-Donia MB (2001) Subchronic dermal application of N, N-diethyl m-toluamide (DEET) and permethrin to adult rats, alone or in combination, causes diffuse neuronal cell death and cytoskeletal abnormalities in the cerebral cortex and the hippocampus, and Purkinje neuron loss in the cerebellum. Exp Neurol 172:153–171

    Article  CAS  Google Scholar 

  • Abou-Donia MB, Wilmarth KR, Abdel-Rahman AA, Jensen KF, Oehme FW, Kurt TL (1996a) Increased neurotoxicity following concurrent exposure to pyridostigmine bromide, DEET, and chlorpyrifos. Fundam App Toxicol Off J Soc Toxicol 34:201–222

    Article  CAS  Google Scholar 

  • Abou-Donia MB, Wilmarth KR, Jensen KF, Oehme FW, Kurt TL (1996b) Neurotoxicity resulting from coexposure to pyridostigmine bromide, deet, and permethrin: implications of Gulf War chemical exposures. J Toxicol Environ Health 48:35–56

    Article  CAS  Google Scholar 

  • Anonymous (1999) Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Stroke 30:2752–2758

    Article  Google Scholar 

  • Anway MD, Cupp AS, Uzumcu M, Skinner MK (2005): Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science (New York, N.Y.) 308:1466–9

  • Anway MD, Rekow SS, Skinner MK (2008): Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis. Reprod Toxicol (Elmsford, N.Y.) 26:100–6

  • Barakat R, Lin PC, Park CJ, Zeineldin M, Zhou S, Rattan S, Brehm E, Flaws JA, Ko CJ (2020) Germline-dependent transmission of male reproductive traits induced by an endocrine disruptor, di-2-ethylhexyl phthalate, in future generations. Sci Rep 10:5705

    Article  CAS  Google Scholar 

  • Braun JM (2017) Early-life exposure to EDCs: role in childhood obesity and neurodevelopment. Nat Rev Endocrinol 13:161–173

    Article  CAS  Google Scholar 

  • Brehm E, Flaws JA (2019) Transgenerational effects of endocrine-disrupting chemicals on male and female reproduction. Endocrinology 160:1421–1435

    Article  CAS  Google Scholar 

  • Cummings AM (1997) Methoxychlor as a model for environmental estrogens. Crit Rev Toxicol 27:367–379

    Article  CAS  Google Scholar 

  • Cupp AS, Skinner MK (2001): Actions of the endocrine disruptor methoxychlor and its estrogenic metabolite on in vitro embryonic rat seminiferous cord formation and perinatal testis growth. Reprod Toxicol (Elmsford, N.Y.) 15:317–26

  • Cupp AS, Uzumcu M, Suzuki H, Dirks K, Phillips B, Skinner MK (2003) Effect of transient embryonic in vivo exposure to the endocrine disruptor methoxychlor on embryonic and postnatal testis development. J Androl 24:736–745

    Article  CAS  Google Scholar 

  • Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, Zoeller RT, Gore AC (2009) Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev 30:293–342

    Article  CAS  Google Scholar 

  • Fisher M, Feuerstein G, Howells DW, Hurn PD, Kent TA, Savitz SI, Lo EH (2009) Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke 40:2244–2250

    Article  Google Scholar 

  • Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS, Toppari J, Zoeller RT (2015) EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals. Endocr Rev 36:E1-e150

    Article  CAS  Google Scholar 

  • Guerrero-Bosagna C, Covert TR, Haque MM, Settles M, Nilsson EE, Anway MD, Skinner MK (2012) Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers. Reprod Toxicol 34:694–707

    Article  CAS  Google Scholar 

  • Hannon PR, Flaws JA (2015) The effects of phthalates on the ovary. Front Endocrinol 6:8

    Article  Google Scholar 

  • Hao C, Gely-Pernot A, Kervarrec C, Boudjema M, Becker E, Khil P, Tevosian S, Jégou B, Smagulova F (2016) Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice. Nucleic Acids Res 44:9784–9802

    CAS  Google Scholar 

  • Kim SS, Lee RD, Lim KJ, Kwack SJ, Rhee GS, Seok JH, Lee GS, An BS, Jeung EB, Park KL (2005) Potential estrogenic and antiandrogenic effects of permethrin in rats. J Reprod Dev 51:201–210

    Article  CAS  Google Scholar 

  • Klukovich R, Nilsson E, Sadler-Riggleman I, Beck D, Xie Y, Yan W, Skinner MK (2019) Environmental toxicant induced epigenetic transgenerational inheritance of prostate pathology and stromal-epithelial cell epigenome and transcriptome alterations: ancestral origins of prostate disease. Sci Rep 9:2209

    Article  Google Scholar 

  • Knoke JD, Gray GC, Garland FC (1998): Testicular cancer and Persian Gulf War service. Epidemiology (Cambridge, Mass.) 9:648–53

  • Lyche JL, Gutleb AC, Bergman A, Eriksen GS, Murk AJ, Ropstad E, Saunders M, Skaare JU (2009) Reproductive and developmental toxicity of phthalates. J Toxic Environ Health Crit Revs 12:225–249

    Article  CAS  Google Scholar 

  • Macleod MR, O’Collins T, Horky LL, Howells DW, Donnan GA (2005) Systematic review and metaanalysis of the efficacy of FK506 in experimental stroke. J Cerebral Blood Flow Metabolism Off J Int Soc Cerebral Blood Flow Metabolism 25:713–721

    Article  CAS  Google Scholar 

  • Manikkam M, Guerrero-Bosagna C, Tracey R, Haque MM, Skinner MK (2012) Transgenerational actions of environmental compounds on reproductive disease and identification of epigenetic biomarkers of ancestral exposures. PloS One 7:e31901

    Article  CAS  Google Scholar 

  • Manikkam M, Tracey R, Guerrero-Bosagna C, Skinner MK (2012b): Pesticide and insect repellent mixture (permethrin and DEET) induces epigenetic transgenerational inheritance of disease and sperm epimutations. Reprod Toxicol (Elmsford, N.Y.) 34:708–19

  • Manikkam M, Tracey R, Guerrero-Bosagna C, Skinner MK (2013) Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PloS One 8:e55387

    Article  CAS  Google Scholar 

  • Manikkam M, Haque MM, Guerrero-Bosagna C, Nilsson EE, Skinner MK (2014) Pesticide methoxychlor promotes the epigenetic transgenerational inheritance of adult-onset disease through the female germline. PloS One 9:e102091

    Article  Google Scholar 

  • McBirney M, King SE, Pappalardo M, Houser E, Unkefer M, Nilsson E, Sadler-Riggleman I, Beck D, Winchester P, Skinner MK (2017) Atrazine induced epigenetic transgenerational inheritance of disease, lean phenotype and sperm epimutation pathology biomarkers. PloS One 12:e0184306

    Article  Google Scholar 

  • Nasuti C, Gabbianelli R, Falcioni ML, Di Stefano A, Sozio P, Cantalamessa F (2007) Dopaminergic system modulation, behavioral changes, and oxidative stress after neonatal administration of pyrethroids. Toxicology 229:194–205

    Article  CAS  Google Scholar 

  • Nilsson E, King SE, McBirney M, Kubsad D, Pappalardo M, Beck D, Sadler-Riggleman I, Skinner MK (2018) Vinclozolin induced epigenetic transgenerational inheritance of pathologies and sperm epimutation biomarkers for specific diseases. PloS One 13:e0202662

    Article  Google Scholar 

  • Patel S, Zhou C, Rattan S, Flaws JA (2015) Effects of endocrine-disrupting chemicals on the ovary. Biol Reprod 93:20

    Google Scholar 

  • Patisaul HB, Adewale HB (2009) Long-term effects of environmental endocrine disruptors on reproductive physiology and behavior. Front Behav Neurosci 3:10

    Article  Google Scholar 

  • Qiu K, Wang J, Chen B, Wang H, Ma C (2020) The effect of breathing exercises on patients with GERD: a meta-analysis. Ann Palliat Med 9:405–413

    Article  Google Scholar 

  • Rattan S, Zhou C, Chiang C, Mahalingam S, Brehm E, Flaws JA (2017) Exposure to endocrine disruptors during adulthood: consequences for female fertility. J Endocrinol 233:R109-r129

    Article  CAS  Google Scholar 

  • Richter CA, Birnbaum LS, Farabollini F, Newbold RR, Rubin BS, Talsness CE, Vandenbergh JG, Walser-Kuntz DR, vom Saal FS (2007): In vivo effects of bisphenol A in laboratory rodent studies. Reprod Toxicol (Elmsford, N.Y.) 24:199–224

  • Rubin BS (2011) Bisphenol A: an endocrine disruptor with widespread exposure and multiple effects. J Steroid Biochem Mol Biol 127:27–34

    Article  CAS  Google Scholar 

  • Sadler-Riggleman I, Klukovich R, Nilsson E, Beck D, Xie Y, Yan W, Skinner MK (2019) Epigenetic transgenerational inheritance of testis pathology and Sertoli cell epimutations: generational origins of male infertility. Environ Epigenet 5:dvz013

  • Sidorkiewicz I, Zaręba K, Wołczyński S, Czerniecki J (2017) Endocrine-disrupting chemicals-Mechanisms of action on male reproductive system. Toxicol Ind Health 33:601–609

    Article  CAS  Google Scholar 

  • Skinner MK (2008): What is an epigenetic transgenerational phenotype? F3 or F2. Reprod Toxicol (Elmsford, N.Y.) 25:2–6

  • Solomon KR, Giesy JP, LaPoint TW, Giddings JM, Richards RP (2013) Ecological risk assessment of atrazine in North American surface waters. Environ Toxicol Chem 32:10–11

    Article  CAS  Google Scholar 

  • Stouder C, Paoloni-Giacobino A (2011) Specific transgenerational imprinting effects of the endocrine disruptor methoxychlor on male gametes. Reproduction (cambridge, England) 141:207–216

    Article  CAS  Google Scholar 

  • Sweeney MF, Hasan N, Soto AM, Sonnenschein C (2015) Environmental endocrine disruptors: Effects on the human male reproductive system. Rev Endocr Metab Disord 16:341–357

    Article  CAS  Google Scholar 

  • Talsness CE, Andrade AJ, Kuriyama SN, Taylor JA, vom Saal FS (2009) Components of plastic: experimental studies in animals and relevance for human health. Philos Trans R Soc Lond, B Biol Sci 364:2079–2096

    Article  CAS  Google Scholar 

  • Thacker NP, Nitnaware VC, Das SK, Devotta S (2007) Dioxin formation in pulp and paper mills of India. Environ Sci Pollut Res Int 14:225–226

    Article  CAS  Google Scholar 

  • Vandenberg LN, Maffini MV, Sonnenschein C, Rubin BS, Soto AM (2009) Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption. Endocr Rev 30:75–95

    Article  CAS  Google Scholar 

  • Xin F, Susiarjo M, Bartolomei MS (2015) Multigenerational and transgenerational effects of endocrine-disrupting chemicals: a role for altered epigenetic regulation? Semin Cell Dev Biol 43:66–75

    Article  CAS  Google Scholar 

  • Young AL, Giesy JP, Jones PD, Newton M (2004) Environmental fate and bioavailability of Agent Orange and its associated dioxin during the Vietnam War. Environ Sci Pollut Res Int 11:359–367

    Article  CAS  Google Scholar 

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Funding

This work was supported by the University Natural Science Research Project of Anhui Province (KJ2018A0165) and by the Nature Science Research Project of Anhui Province (NO. 2108085MH305).

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Authors and Affiliations

  1. Department of Occupational and Environmental Health, School of Public Health, Anhui Medical University, Meishan Rd 81, Hefei, 230032, China

    Huan He, Wenjing Chen, Yu Wei, Taifa Zhang, Wenfeng Geng & Jinxia Zhai

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  1. Huan He
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  2. Wenjing Chen
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  3. Yu Wei
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  4. Taifa Zhang
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  5. Wenfeng Geng
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  6. Jinxia Zhai
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Contributions

Huan He and Yu Wei had the idea for the article. Huan He, Wenfeng Geng, and Wenjing Chen reviewed the literature. Huan He, Yu Wei, and Taifa Zhang checked and managed the data. Huan He and Yu Wei performed data analysis. Huan He, Yu Wei, and Wenfeng Geng drafted the manuscript. Jinxia Zhai, Wenfeng Geng, and Taifa Zhang provided expert reviews of the manuscript and reviewed and approved the manuscript. All authors contributed to the research article and approved the final version.

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Correspondence to Jinxia Zhai.

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He, H., Chen, W., Wei, Y. et al. Effects of perinatal exposure to endocrine-disrupting chemicals on the reproductive system of F3 generation male rodents: a meta-analysis. Environ Sci Pollut Res 29, 33218–33229 (2022). https://doi.org/10.1007/s11356-021-18338-w

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