DOI QR코드

DOI QR Code

Hershberger Assays for Bisphenol-A and Its Substitute Candidates

  • Kim, Hee-Su (Dept. of Biotechnology, Sangmyung University) ;
  • Kim, Yong-Bin (Dept. of Biotechnology, Sangmyung University) ;
  • Choi, Donchan (Dept. of Life Science, Yong-In University) ;
  • Cheon, Yong-Pil (Division of Developmental Biology and Physiology, Sungshin University) ;
  • Lee, Sung-Ho (Dept. of Biotechnology, Sangmyung University)
  • Received : 2017.10.21
  • Accepted : 2017.12.10
  • Published : 2017.12.31

Abstract

Bisphenol-A(BPA) is a member of alkylphenol family, and shows adverse effects including reduced fertility, reproductive tract abnormalities, metabolic disorder, cancer induction, neurotoxicity and immunotoxicity. In the present study, we conducted Hershberger assay to evaluate whether the two candidates to replace BPA have androgenic or antiandrogenic activity. The assay was carried out using immature castrated Sprague-Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were BPA, isosorbide (ISO) and cyclohexanedimethanol (CHDM). The rats were necropsied, and then the weights of five androgen-dependent tissues [ventral prostate, seminal vesicle, levator ani-bulbocavernosus (LABC) muscle, paired Cowper's glands, and glans penis] and three androgen-insensitive tissues (kidney, spleen and liver) were measured. All test materials including BPA did not exhibit any androgenic activity in the assay. On the contrary, antiandrogen-like activities were found in all test groups, and the order of the intensity was CHDM > BPA > ISO in the five androgen-sensitive tissues. There was no statistical difference between low dose treatment and high dose treatment of BPA group as well as ISO group. In CHDM group, high dose treatment exhibited most severe weight reduction in all measured tissues. There was no statistical difference in androgen-insensitive tissue measurements, except BPA groups. Since the effects of ISO treatment on the accessory sex organs were much less or not present at all when compared to those of BPA, ISO could be a strong candidate to replace BPA. CHDM treatment brought most severe weight reduction in all of androgen-sensitive tissues, so this material should be excluded for further screening of BPA substitute selection.

Keywords

References

  1. Bjornsdotter MK, de Boer J, Ballesteros-Gomez A (2017) Bisphenol A and replacements in thermal paper: A review. Chemosphere 182:691-706. https://doi.org/10.1016/j.chemosphere.2017.05.070
  2. Costa EM, Spritzer PM, Hohl A, Bachega TA (2014) Effects of endocrine disruptors in the development of the female reproductive tract. Arq Bras Endocrinol Metabol 58:153-161. https://doi.org/10.1590/0004-2730000003031
  3. Devillers J, Marchand-Geneste N, Carpy A, Porcher JM (2006) SAR and QSAR modeling of endocrine disruptors. SAR QSAR Environ Res 17:393-412. https://doi.org/10.1080/10629360600884397
  4. Dickerson SM, Gore AC (2007) Estrogenic environmental endocrine-disrupting chemical effects on reproductive neuroendocrine function and dysfunction across the life cycle. Rev Endocr Metab Disord 8:143-159. https://doi.org/10.1007/s11154-007-9048-y
  5. Eladak S, Grisin T, Moison D, Guerquin MJ, N'Tumba-Byn T, Pozzi-Gaudin S, Benachi A, Livera G, Rouiller-Fabre V, Habert R (2015). A new chapter in the bisphenol A story: bisphenol S and bisphenol F are not safe alternatives to this compound. Fertil Steril 103:11-21. https://doi.org/10.1016/j.fertnstert.2014.11.005
  6. Giulivo M, Lopez de Alda M, Capri E, Barcelo D (2016) Human exposure to endocrine disrupting compounds: Their role in reproductive systems, metabolic syndrome and breast cancer. A review. Environ Res 151:251-264. https://doi.org/10.1016/j.envres.2016.07.011
  7. EDSP (1998) Endocrine Disruptor Screening Program (EDSP) Hershberger Assay OCSPP Guideline 890.1400 Standard Evaluation Procedure (SEP). US Environmental Protection Agency.
  8. Ho SM, Tang WY, Belmonte de Frausto J, Prins GS (2006). Developmental exposure to estradiol and bisphenol A increases susceptibility to prostate carcinogenesis and epigenetically regulates phosphodiesterase type 4 variant 4. Cancer Res 66:5624-5632. https://doi.org/10.1158/0008-5472.CAN-06-0516
  9. Itoh K, Yaoi T, Fushiki S (2012) Bisphenol A, an endocrine-disrupting chemical, and brain development. Neuropathology. 32:447-457. https://doi.org/10.1111/j.1440-1789.2011.01287.x
  10. Karwacka A, Zamkowska D, Radwan M, Jurewicz J (2017) Exposure to modern, widespread environmental endocrine disrupting chemicals and their effect on the reproductive potential of women: an overview of current epidemiological evidence. Hum Fertil (Camb) 31:1-24.
  11. Kim HS, Han SY, Kim TS, Kwack SJ, Lee RD, Kim IY, Seok JH, Lee BM, Yoo SD, Park KL (2002) No androgenic/anti-androgenic effects of bisphenol-A in Hershberger assay using immature castrated rats. Toxicol Lett 135:111-123. https://doi.org/10.1016/S0378-4274(02)00130-3
  12. Kimber I (2017) Bisphenol A and immunotoxic potential: A commentary. Regul Toxicol Pharmacol 90:358-363. https://doi.org/10.1016/j.yrtph.2017.08.022
  13. McLachlan JA (2016) Environmental signaling: from environmental estrogens to endocrine-disrupting chemicals and beyond. Andrology 4:684-694. https://doi.org/10.1111/andr.12206
  14. MacKay H, Abizaid A (2017) A plurality of molecular targets: The receptor ecosystem for bisphenol-A (BPA). Horm Behav. 2017 Nov 14. pii: S0018-506X(17)30311-2. doi: 10.1016/j.yhbeh.2017.11.001. [Epub ahead of print]
  15. Manfo FP, Jubendradass R, Nantia EA, Moundipa PF, Mathur PP (2014) Adverse effects of bisphenol A on male reproductive function. Rev Environ Contam Toxicol 228:57-82.
  16. Marty MS, O'Connor JC (2014) Key learnings from the Endocrine Disruptor Screening Program (EDSP) Tier 1 rodent uterotrophic and Hershberger assays. Birth Defects Res B Dev Reprod Toxicol 101:63-79. https://doi.org/10.1002/bdrb.21098
  17. Meeker JD (2012) Exposure to environmental endocrine disruptors and child development. Arch Pediatr Adolesc Med 166:952-958.
  18. Nimrod AC, Benson WH (1996) Environmental estrogenic effects of alkylphenol ethoxylates. Crit Rev Toxicol 26:335-364. https://doi.org/10.3109/10408449609012527
  19. Nishino T, Wedel T, Schmitt O, Schonfelder M, Hirtreiter C, Schulz T, Kuhnel W, Michna H (2006) The xenoestrogen bisphenol A in the Hershberger assay: androgen receptor regulation and morphometrical reactions indicate no major effects. J Steroid Biochem Mol Biol 98:155-163. https://doi.org/10.1016/j.jsbmb.2005.08.019
  20. OECD (2007) OECD test guideline 440 uterotrophic bioassay in rodents: a short-term screening test for oestrogenic properties.
  21. OECD (2008) Draft OECD guideline for the testing of chemicals. The Hershberger bioassay in rats: A short term test for (anti) androgenic properties.
  22. Pivnenko K, Pedersen GA, Eriksson E, Astrup TF (2015) Bisphenol A and its structural analogues in household waste paper. Waste Manag 44:39-47. https://doi.org/10.1016/j.wasman.2015.07.017
  23. 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 24:199-224. https://doi.org/10.1016/j.reprotox.2007.06.004
  24. Rochester JR, Bolden AL (2015) Bisphenol S and F: A systematic review and comparison of the hormonal activity of bisphenol a substitutes. Environ Health Perspect 123:643-650. https://doi.org/10.1289/ehp.1408989
  25. Rubin BS (2011) Bisphenol A: An endocrine disruptor with widespread exposure and multiple effects. J Steroid Biochem Mol Bio 127:27-34. https://doi.org/10.1016/j.jsbmb.2011.05.002
  26. Sifakis S, Androutsopoulos VP, Tsatsakis AM, Spandidos DA (2017) Human exposure to endocrine disrupting chemicals: Effects on the male and female reproductive systems. Environ Toxicol Pharmacol 51:56-70. https://doi.org/10.1016/j.etap.2017.02.024
  27. Teng C, Goodwin B, Shockley K, Xia M, Huang R, Norris J, Merrick BA, Jetten AM, Austin CP, Tice RR (2013) Bisphenol A affects androgen receptor function via multiple mechanisms. Chem Biol Interact 203:556-564. https://doi.org/10.1016/j.cbi.2013.03.013
  28. WHO (2013) State of the science of endocrine disrupting chemicals - 2012. World Health Organization. Retrieved 2015-04-06.
  29. Yoon K, Kwack SJ, Kim HS, Lee BM (2014) Estrogenic endocrine-disrupting chemicals: molecular mechanisms of actions on putative human diseases. J Toxicol Environ Health B Crit Rev 17:127-174. https://doi.org/10.1080/10937404.2014.882194