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Bisphenol a induces reproductive dysfunction in male mice

  • Young-Joo, Yi (Department of Agricultural Education, College of Education, Sunchon National University) ;
  • Malavige Romesha, Chandanee (Department of Agricultural Education, College of Education, Sunchon National University) ;
  • Dong-Won, Seo (Department of Vaccine, Gyeongbuk Institute for Bio industry) ;
  • Jung-Min, Heo (College of Agriculture and Life Sciences, Department of Animal Science and Biotechnology, Chungnam National University) ;
  • Min, Cho (Division of Biotechnology, SELS center, College of Environmental & Bioresource Sciences, Jeonbuk National University) ;
  • Sang-Myeong, Lee (Laboratory of Veterinary Virology, College of Veterinary Medicine, Chungbuk National University)
  • Received : 2021.10.21
  • Accepted : 2021.11.11
  • Published : 2021.12.01

Abstract

It has been suggested that bisphenol A (BPA), a known endocrine disruptor, interferes with the endocrine system, causing reproductive dysfunction. Recently, BPA has been found in waste water due to incomplete sewage purification, possibly threatening health through its ingestion via tap water. In this study, young male mice (6 - 7 weeks old) were administered water containing BPA (50 mg·kg-1) for four weeks, while control mice consumed water without BPA. Serum, epididymal spermatozoa and testicular sections were assessed after sacrificing the mice on day 28. No significant differences were obtained between the groups in the body, testis and seminal vesicle weights. However, the epididymal sperm motility and count levels were significantly reduced in BPA-fed mice. Significantly higher hepatotoxicity levels were also observed in mice ingesting BPA as compared to the control mice. The level of serum testosterone was reduced, and testicular sections revealed incomplete and irregular spermatogenesis in BPA-ingested mice. The sperm proteasomal-proteolytic activity level has been implicated in sperm function and is measured in motile spermatozoa using fluorometric substrates. High ubiquitin C-terminal hydrolase activity levels were observed in the control mice without BPA. During a mating trial, a low pregnancy rate (71.4%) was observed in females mated with males who had consumed BPA (100% in the control mice). Overall, BPA adversely affected spermatogenesis and quality, as indicated by decreased sperm motility, concentration and serum testosterone levels, resulting in reduced fertility competence.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government(MSIT) (NRF-2013R1A6A3A04063769 and NRF-2020R1A2C1014007).

References

  1. Al-Hiyasat AS, Darmani H, Elbetieha AM. 2002. Effects of bisphenol A on adult male mouse fertility. European Journal of Oral Sciences 110:163-167. https://doi.org/10.1034/j.1600-0722.2002.11201.x
  2. Angle BM, Do RP, Ponzi D, Stahlhut RW, Drury BE, Nagel SC, Welshons WV, Besch-Williford CL, Palanza P, Parmigiani S, et al. 2013. Metabolic disruption in male mice due to fetal exposure to low but not high doses of bisphenol A (BPA): Evidence for effects on body weight, food intake, adipocytes, leptin, adiponectin, insulin, and glucose regulation. Reproduction Toxicology 42:256-268. https://doi.org/10.1016/j.reprotox.2013.07.017
  3. Cariati F, D'Uonno N, Borrillo F, Iervolino S, Galdiero G, Tomaiuolo R. 2019. Bisphenol A: An emerging threat to male fertility. Reproductive Biology and Endocrinology 17:1-8. https://doi.org/10.1186/s12958-018-0446-7
  4. Casey MF, Neidell M. 2013. Disconcordance in statistical models of bisphenol A and chronic disease outcomes in NHANES 2003-08. PloS ONE 8:79944.
  5. Castellini C, Totaro M, Parisi A, D'Andrea S, Lucente L, Cordeschi G, Francavilla S, Francavilla F, Barbonetti A. 2020. Bisphenol A and male fertility: Myths and realities. Frontiers in Endocrinology 11:353.
  6. Chitra KC, Latchoumycandane C, Mathur PP. 2003. Induction of oxidative stress by bisphenol A in the epididymal sperm of rats. Toxicology 185:119-127. https://doi.org/10.1016/S0300-483X(02)00597-8
  7. Corrales J, Kristofco LA, Steele WB, Yates BS, Breed CS, Williams ES, Brooks BW. 2015. Global assessment of bisphenol A in the environment: Review and analysis of its occurrence and bioaccumulation. Dose-Response JulySeptember 2015:1-29.
  8. Dobrzynska MM, Radzikowska J. 2013. Genotoxicity and reproductive toxicity of bisphenol A and X-ray/bisphenol A combination in male mice.Drug and Chemical Toxicology 36:19-26. https://doi.org/10.3109/01480545.2011.644561
  9. EFSA (European Food Safety Authority) Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF). 2015. Scientific opinion on the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs. EFSA Journal 13:3978.
  10. Elhamalawy OH, Eissa FI, El Makawy AI, El-Bamby MM. 2018. Bisphenol-A hepatotoxicity and the protective role of sesame oil in male mice. Jordan Journal of Biological Sciences 11:461-467.
  11. Gu Z, Jia R, He Q, Cao L, Du J, Feng W, Jeney G, Xu P, Yin G. 2021. Alteration of lipid metabolism, autophagy, apoptosis, and immune response in the liver of common carp (Cyprinus carpio) after long-term exposure to bisphenol A. International Society of Ecotoxicology and Environmental Safety 211:111923.
  12. Hughes PJ, McClellan H, Lowes Da, Kahn SZ, Bilmen JG, Tovey SC, Godfrey RE, Michell RH, Kirk CJ, Michelangeli F. 2000. Estrogenic alkylphenols induce cell death by inhibiting testis endoplasmic reticulum Ca2+ pumps. Biochemical and Biophysical Research Communications 277:568-574. https://doi.org/10.1006/bbrc.2000.3710
  13. Jin P, Wang X, Chang F, Bai Y, Li Y, Zhou R, Chen L. 2013. Low dose bisphenol A impairs spermatogenesis by suppressing reproductive hormone production and promoting germ cell apoptosis in adult rats. Journal of Biomedical Research 27:135-144.
  14. Kabuto H, Amakawa M, Shishibori T. 2004. Exposure to bisphenol A during embryonic/fetal life and infancy increases oxidative injury and causes underdevelopment of the brain and testis in mice. Life Sciences 74:2931-2940. https://doi.org/10.1016/j.lfs.2003.07.060
  15. Liguori F, Moreno-Marrodan C, Barbaro P. 2020. Biomass-derived chemical substitutes for bisphenol A: Recent advancements in catalytic synthesis. Chemical Society Reviews 49:6329-6363. https://doi.org/10.1039/d0cs00179a
  16. Minguez-Alarcon L, Hauser R, Gaskins AJ. 2016. Effects of bisphenol A on male and couple reproductive health: A review. Fertility and Sterility 106:864-870. https://doi.org/10.1016/j.fertnstert.2016.07.1118
  17. Moriyama K, Tagami T, Akamizu T, Usui T, Saijo M, Kanamoto N, Hataya Y, Shimatsu A, Kuzuya H, Nakao K. 2002. Thyroid hormone action is disrupted by bisphenol A as an antagonist. The Journal of Clinical Endocrinology & Metabolism 87:5185-5190. https://doi.org/10.1210/jc.2002-020209
  18. Rahman MS, Pang WK, Ryu DY, Park YJ, Ryu BY, Pang MG. 2021. Multigenerational impacts of gestational bisphenol A exposure on the sperm function and fertility of male mice. Journal of Hazarous Materials 416:125791.
  19. Reitman S, Frankel SA. 1957. Colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. American Journal of Clinical Pathology 28:56-63. https://doi.org/10.1093/ajcp/28.1.56
  20. 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. Reproductive Toxicology 24:199-224. https://doi.org/10.1016/j.reprotox.2007.06.004
  21. Rochester JR. 2013. Bisphenol A and human health: A review of the literature. Reproduction Toxicology 42:132-155. https://doi.org/10.1016/j.reprotox.2013.08.008
  22. Rykowska I, Wasiak W. 2006. Properties, threats, and methods of analysis of bisphenol A and its derivatives. Acta Chromatographica 16:7-27.
  23. Sangai NP, Verma RJ. 2012. Protective effect of quercetin on bisphenol A-caused alterations in succinate dehydrogenase and adenosine triphosphatase activities in liver and kidney of mice. Acta Poloniae PharmaceuticaDrug Research 69:1189-1194.
  24. Santiago J, Silva JV, Santos MAS, Fardilha M. 2021. Fighting bisphenol A-induced male infertility: The power of antioxidants. Antioxidants 10:289.
  25. Serra H, Beausoleil C, Habert R, Minier C, Picard-Hagen N, Michel C. 2019. Evidence for Bisphenol B endocrine properties: Scientific and regulatory perspectives. Environmental Health Perspectives 127:106001.
  26. Suarez SS. 2008. Control of hyperactivation in sperm. Human Reproduction 14:647-657.
  27. Sutovsky P. 2011. Sperm proteasome and fertilization. Reproduction 142:1-14. https://doi.org/10.1530/REP-11-0041
  28. Tourmente M, Villar-Moya P, Rial E, Roldan ER. 2015. Differences in ATP generation via glycolysis and oxidative phosphorylation and relationships with sperm motility in mouse species. Journal of Biological Chemistry 290:20613-20626.
  29. Wetherill YB, Akingbemi BT, Kanno J, McLachlan JA, Nadal A, Sonnenschein C, Watson CS, Zoeller RT, Belcher SM. 2007. In vitro molecular mechanisms of bisphenol A action. Reproductive Toxicology 24:178-198. https://doi.org/10.1016/j.reprotox.2007.05.010
  30. Wetherill YB, Petre CE, Monk KR, Puga A, Knudsen KE. 2002. The xenoestrogen bisphenol A induces inappropriate androgen receptor activation and mitogenesis in prostatic adenocarcinoma cells. Molecular Cancer Therapeutics 1:515-524.
  31. Yi YJ, Adikari AADI, Moon ST, Heo JM, Lee SM. 2021. Adverse effect of IL-6 on the in vitro maturation of porcine oocytes. Korean Journal of Agricultural Science 48:607-615. https://doi.org/10.7744/KJOAS.20210051
  32. Yi YJ, Sutovsky M, Kennedy C, Sutovsky P. 2012. Identification of the inorganic pyrophosphate metabolizing, ATP substituting pathway in mammalian spermatozoa. PloS ONE 7:34524.
  33. Zhang Y, Han L, Yang H, Pang J, Li P, Zhang G, Li F, Wang F. 2017. Bisphenol A affects cell viability involved in autophagy and apoptosis in goat testis Sertoli cell. Environmental Toxicology and Pharmacology 55:137-147. https://doi.org/10.1016/j.etap.2017.07.014
  34. Zoeller RT, Bansal R, Parris C. 2005. Bisphenol-A, an environmental contaminant that acts as a thyroid hormone receptor antagonist in vitro, increases serum thyroxine, and alters RC3/neurogranin expression in the developing rat brain. Endocrinology 146:607-612.  https://doi.org/10.1210/en.2004-1018