Environmental Analysis Health and Toxicology

환경독성보건학회 (The Korean Society of Environmental Health and Toxicology)
권호 표지

임신 및 수유기간 동안 Bisphenol A Diglycidyl Ether 노출에 의한 랏트 부고환 clusterin mRNA 발현량 감소

Decreased of Clusterin mRNA Expression of Epididymis Following Exposure to Bisphenol A Diglycidyl Ether during Gestation and Lactation in Sprague-Dawley Rats

  • 강대웅 (중앙대학교 의과대학 예방의학교실) ;
  • 권수경 (중앙대학교 의과대학 예방의학교실) ;
  • 양윤정 (중앙대학교 의과대학 예방의학교실) ;
  • 천영진 (중앙대학교 약학대학) ;
  • 홍연표 (중앙대학교 의과대학 예방의학교실)
  • Kang, Dae-Woong (Department of Preventive Medicine, College of Medicine, Chung-Ang University) ;
  • Kwon, Su-Kyoung (Department of Preventive Medicine, College of Medicine, Chung-Ang University) ;
  • Yang, Yun-Jung (Department of Preventive Medicine, College of Medicine, Chung-Ang University) ;
  • Chun, Young-Jin (College of Pharmacy, Chung-Ang University) ;
  • Hong, Yeon-Pyo (Department of Preventive Medicine, College of Medicine, Chung-Ang University)
  • 발행 : 2008.12.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Bisphenol A diglycidyl ether(BADGE)는 비스페놀 A와 에피클로로하이드린의 축합에 의해 만들어지는 물질로 상업용 액상 에폭시 수지의 주성분이다. 본 연구는 clusterin mRNA 발현이 BADGE의 노출된 생식기계 독성에 연관되어 있는지를 연구하기 위해 수행하였다. BADGE는 SPF Sprague-Dawley 임신 랏트에 임신 6일부터 수유기가지 하루에 한 번 0(대조군)과 375mg/kg/day를 경구 투여하였다. 수컷 새끼는 일반 사항과 몸무게, 일반 발달 지표(예, 항문과 생식기 사이의 거리, 이개개전, 절치붕출, 유두잔류, 안검개열, 고환하강, 포피박리 등)등을 관찰하였다. 대조군과 투여군에서 다섯 마리의 수컷 새끼는 출생 후 3, 6와 9주에 부검하여 부고환의 조직학적 변화 등을 관찰하였다. BADGE 375 mg/kg/day 투여군에서 항문과 생식기 사이의 거리는 대조군보다 길어지는 경향을 보였다. 출생 후 6주와 9주에서 부고환의 상대 무게는 대조군보다 약간 증가하였으나 조직학적인 변화는 관찰되지 않았다. BADGE 투여 군에서 clusterin mRNA 발현량은 대조군에 비해 3주에 56%, 6주에 57% 그리고 9주에 86% 감소하였다. 이런 결과는 랏트의 부고환에서 clusterin은 BADGE에 반응하는 유전자 중 하나일 수 있다는 가능성을 나타낸다.

키워드

참고문헌

  1. Blaschuk O, Burdzy K and Fritz IB. Purification and characterization of a cell-aggregating factor (clusterin), the major glycoprotein in ram rete testis fluid, J Biol Chem 1983; 258: 7714-7720
  2. Graham S and Gandelman R. The expression of ano-genital distance data in the mouse, Physiol Behav 1986; 36: 103-104 https://doi.org/10.1016/0031-9384(86)90081-8
  3. Hanley TR, Hagler AR, Sullivan VD and Stebbins KE. DGEBPA: Two Generation Oral Gavage Study in Sprague- Dawley Rats. 1996 (Midland: Dow Chemical Co.)
  4. Hinton BT, Palladino MA, Rudolph D, Lan ZJ and Lobus JC. The role of the epididymis in the protection of spermatozoa, Dev Biol 1996; 33: 61-102
  5. Hinton BT and Palladino MA. Epididymal epithelium:its contribution to the formation of a luminal fluid microenvironment, Microsc Res Tech 1995; 30: 67-81 https://doi.org/10.1002/jemt.1070300106
  6. Hyung UJ, Yang YJ, Kwon SK, Yoo JH, Myoung SC, Kim SC and Hong YP. Developmental toxicity study of bisphenol A diglycidyl ether in Sprague-Dawley male rats during pregnancy and lactation, J Prev Med Pub Health 2007; 40: 155-161 https://doi.org/10.3961/jpmph.2007.40.2.155
  7. Im JU, Yang YJ, Lee TJ and Hong YP. Acute toxicity of administered bisphenol a diglycidyl ether in male sprague dawley rats, Korean J Occup Environ Med 2006;18(4): 318-326
  8. International Agency for Research on Cancer (IARC). Bisphenol A diglcidyl ether. In: IARC Monographs on Evaluation of Carcinogenic Risks in Humans. IARC. Lyon. 1999. 1285-1289
  9. Jolanki R, Kanerva L and Kanerva L. Occupational contact dermatitis and contact urticaria caused by epoxy resins, Acta Derm Venerol Suppl(Stockh) 1987; 134: 90-94
  10. Jolanki R, Kanerva L, Estlander T, Tarvainen K, Keskinen H and Henriks-Eckerman ML. Occupational dermatoses from epoxy resin compounds, Contact Dermatitis 1990;23: 172-183 https://doi.org/10.1111/j.1600-0536.1990.tb04779.x
  11. Kanerva L, Estlander T and Jolanki R. Occupational skin disease in Finland: an analysis of 10 years of statistics from an occupational dermatology clinic, Int Arch Occup Environ Health 1988; 60: 89-94 https://doi.org/10.1007/BF00381486
  12. Kissinger C, Skinner MK and Griswold MD. Analysis of Sertoli cell-secreted proteins by two-dimensional gel electrophoresis, Biol Reprod 1982; 27: 233-240 https://doi.org/10.1095/biolreprod27.1.233
  13. Leblond CP and Clermont Y. Definition of the stages of the cycle of the seminiferous epithelium in the rat, Ann NY Acad Sci 1952; 55: 548-573 https://doi.org/10.1111/j.1749-6632.1952.tb26576.x
  14. Lee C, Janulis L, Ilio K, Shah A, Park I, Kim S, Cryns V, Pins M and Bergan R. In vitro models of prostate apoptosis: clusterin as an antiapoptotic mediator, Prostate Supple 2000; 9: 21-24
  15. lea N, Pulgar R, Perez P, Olea-Serrano F, Rivas A, Novillo Fertrell A, Pedraza V, Soto AM and Sonnenschein C. Estrogenicity of resin-base composites and sealants used in dentistry, Environ Health Perspect 1996; 104: 298-305 https://doi.org/10.2307/3432888
  16. Perez P, Pulgar R, Olea-Serrano F, Villalobos M, Rivas A, Metzler M, Pedraza V and Olea N. The estrogenicity of bisphenol A-related diphenylalkanes with various substituents at the central carbon and the hydroxy groups, Environ Health Perspect 1998; 106: 167-174 https://doi.org/10.2307/3434318
  17. Poole A, van Herwijnen P, Weideli H, Thomas MC, Ransbotyn G and Vance C. Review of the toxicology, human exposure and safety assessment for bisphenol A diglycidyl ether (BADGE), Food Addit Contam 2004; 21: 905-919 https://doi.org/10.1080/02652030400007294
  18. Pucci S, Bonnano E, Pichiorri F, Angeloni C and Spagnoli LG. Modulation of different clusterin isoforms in huma colon tumorigenesis, Oncogene 2004; 23(13): 2298-2304 https://doi.org/10.1038/sj.onc.1207404
  19. Savkovic V, Gaiser S, Iovanna JL and Bodeker H. The stress response of the exocrine pancreas, Dig Dis 2004; 22:239-246 https://doi.org/10.1159/000082795
  20. Schwochau GB, Nath KA and Rosenberg ME. Clusterin protests against oxidative stress in vitro through aggregative and nonaggregative properties, Kidney Int 1998; 53:1647-1653 https://doi.org/10.1046/j.1523-1755.1998.00902.x
  21. Sheehan DM, Willingham E, Gaylor D, Bergeron JM and Crews D. No threshold dose for oestradiol-induced sex reversal of turtle embryos: how little is too much?, Environ Health Perspect 1999; 107: 155-159 https://doi.org/10.1289/ehp.99107s1155
  22. Smith JA, Masters RE and Dawe IS. A Study of the Effect of TK 10490 on the Reproductive Function of One Generation in the rat, 1989; Report
  23. Sylvester SR, Morales C, Oko R and Griswold MD. Localization of sulfated glycoprotein-2 (clusterin) on spermatozoa and in the reproductive tract of the male rat, Biol Reprod 1991; 45: 195-207 https://doi.org/10.1095/biolreprod45.1.195
  24. Tenniswood MP, Guenette RS, Lakins J, Mooibroek M, Wong P and Welsh, JE. Active cell death in hormonedependent tissues, Cancer Metastasis Rev 1992; 11:197-220 https://doi.org/10.1007/BF00048064
  25. Thimon V, Koukoui O, Calvo E and Sullivan R. Regionspecific gene expression profiling along the human epididymis, Mol Hum Reprod 2007; 13(10): 691-704 https://doi.org/10.1093/molehr/gam051
  26. Thorgerisson A and Fregert S. Allergenicity of epoxy resins in the guinea pig, Acta Derm Venerol(Stockh) 1977; 57:253-256
  27. Thorgerisson A, Fregert S and Ramnas O. Sensitization capacity of epoxy resin oligomers in the guinea pig, Acta Derm Venerol(Stockh) 1978; 58(1): 17-21
  28. Thomas-Salgar S and Millis AJ. Clusterin expression in differentiating smooth muscle cells, J Biol Chem 1994;269(27): 17879-17885
  29. Trougakos IP, So A, Jansen B, Gleave ME and Gonos ES. Silencing expression of the clusterin/apolipoprotein j gene in human cancer cells using small interfering RNA induces spontaneous apoptosis, reduced growth ability, and cell sensitization to genotoxic and oxidative stress, Cancer Res 2004; 64(5): 1834-1842 https://doi.org/10.1158/0008-5472.CAN-03-2664
  30. vom Saal FS, Timms BG, Montano MM, Palanza P, Thayer KA, Nagel SC, Dhar MD, Ganjam VK, Oarmigiani S and Welshons WV. Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses, Proc Natl Acad Sci USA 1997; 94: 2056-2061
  31. Wilson MR and Easterbrook-Smith SB. Clusterin is a secreted mammalian chaperone, Trends Biochem Sci 2000;25(3): 95-98 https://doi.org/10.1016/S0968-0004(99)01534-0
  32. Wolf MA. Unpublished report (Midland: Dow Chemical Co.). 1958
  33. World Wildlife Fund (WWF). Bisphenol A. A WWF European Toxics Programme Report. 2000; (http://www.panda.org/downloads/toxics/bisphenol.pdf)
  34. Zambrano E, Rodriguez-Gonzalez GL, Guzman C, Garcia-Becerra R, Boeck L, Diaz L, Menjivar M, Larrea F and Nathanielsz PW. A maternal low protein diet during pregnancy and lactation in the rat impairs male reproductive development, J Physiol 2005; 563(1): 275-284 https://doi.org/10.1113/jphysiol.2004.078543