Development and Reproduction (한국발생생물학회지:발생과생식)

The Korean Society of Developmental Biology (한국발생생물학회)
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Simazine-induced Alteration of the Expression Levels of Apoptosis- and Steroidogenesis-regulating Genes in Testicular Cells

Simazine이 정소세포에서 Apoptosis와 Steroidogenesis 조절 유전자들의 발현에 미치는 영향

  • 박호옥 (차의과학대학교 약학대학 약학과) ;
  • 고정재 (차의과학대학교 의생명대학 의생명과학과) ;
  • 배지현 (차의과학대학교 약학대학 약학과)
  • Received : 2011.05.21
  • Accepted : 2011.06.14
  • Published : 2011.06.30
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Abstract

Simazine (6-chloro-N,N'-diethyl-1,3,5-triazine-2,4-diamine) is a triazine herbicide that has been applied worldwide including Korea for agricultural purposes. Simazine is the second most commonly detected pesticide in surfaceand ground-water in the United States, Europe and Australia. It has been shown that simazine is a potent endocrine disruptor in wildlife and laboratory animals. Although many endocrine disruptors can induce apoptosis in various types of cells, the effects of simazine on apoptosis and on the expression of Bcl-2 family genes are not known. Also it is unknown the effect of simazine on the expression of steroidogenesis-regulating genes in testicular cells. In this study, we investigated the effect of simazine on the expression levels of apoptosis- and steroidogenesis-regulating genes in testicular cells. We found that a low concentration of simazine can alter the mRNA expression levels of steroidogenesis-related genes and Bcl-2 family genes in mouse Sertoli cells and rat Leydig cells. Thus, our results suggest that simazine can disturb normal testicular development and reproductive function by altering the expression of genes that are critical for the regulation of apoptosis and steroidogenesis.

Simazine은 triazine계 제초제로서, 잡초와 일년생 풀들을 통제하는데 우리나라를 포함하여 세계적으로 널리 사용되고 있으며, 미국, 유럽, 오스트레일리아의 경우, 물에서 두 번째로 많이 검출되는 살충제로 알려져 있다. Simazine에오염된 토양과 물을 통하여 사람에게 노출되어 이후 생체 내에 수년간 잔존하며 특히, 생물체의 지방 및 조직에 농축되는특징을 갖는 내분비계 장애물질로 분류되어졌다. 하지만 simazine이 정소세포의 사멸 또는 생존에 미치는 영향과 세포예정사를 관장하는 Bcl-2 family 유전자 발현에 미치는 영향을 보고한 연구는 없다. 또한 simazine이 성의 분화와 생식기관발달에 중요한 steroidogenesis 관련 유전자의 발현에 미치는 영향 분석에 관한 연구도 미흡한 실정이다. 따라서 본 연구진은 이번 연구에서 simazine이 mouse Sertoli 세포와 rat Leydig 세포에서 세포사멸을 관장하는 Bcl-2 family 유전자군의발현과 steroidogenesis 조절관련 유전자군의 발현 변화에 미치는 영향을 조사하였고, simazine이상기 유전자군의 정상적인 발현을 저해함을 확인하였다. 그러므로 본 연구의 결과로 미루어 볼 때, 사람이나 기타 동물 등이 simazine에 장시간 노출될 경우, 생식 세포에 apoptosis가 유도될 수 있는 가능성을 제시하였으며, steroidogenesis 조절관련 유전자군의 발현을 교란시킴으로써, 정상적인 testis의 발달을 저해하여 남성 생식계의 기능장애를 유도할 가능성이 있음을 제시하였다.

Keywords

References

  1. Almeida J, Conley A, Mathewson L, Ball BA (2011) Expression of steroidogenic enzymes during equine testicular development. Reproduction.
  2. Andersen HR, Vinggaard AM, Rasmussen TH, GjErmandsen IM, Bonefeld-Jorgensen EC (2002) Effects of currently used pesticides in assays for estrogenicity, androgenicity, and Aromatase activity in vitro. Toxicol Appl Pharmacol 179:1-12. https://doi.org/10.1006/taap.2001.9347
  3. Anway MD, Cupp AS, Uzumcu M, Skinner MK (2005) Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308:1466-1469. https://doi.org/10.1126/science.1108190
  4. Babic-Gojmerac T, Kniewald Z, Kniewald J (1989) Testosterone metabolism in neuroendocrine organs in male rats under atrazine and deethylatrazine influence. J Steroid Biochem 33:141-146. https://doi.org/10.1016/0022-4731(89)90369-5
  5. Birkhoj M, Nellemann C, Jarfelt K, Jacobsen H, Andersen HR, Dalgaard M, Vinggaard AM (2004) The combined antiandrogenic effects of five commonly used pesticides. Toxicol Appl Pharmacol 201:10-20. https://doi.org/10.1016/j.taap.2004.04.016
  6. Cooper RL, Stoker TE, Tyrey L, Goldman JM, Mcelroy WK (2000) Atrazine disrupts the hypothalamic control of pituitary-ovarian function. Toxicol Sci 53:297-307. https://doi.org/10.1093/toxsci/53.2.297
  7. Han X, Tu Z, Wang X, Shen S, Hou Y (2004) Nonylphenol induced apoptosis in rat testis through the Fas/FasL pathway. Bull Environ Contam Toxicol 73:620-627.
  8. Hayes T, Haston K, Tsui M, Hoang A, Haeffele C, Vonk A (2003) Atrazine-induced hermaphroditism at 0.1 ppb in American leopard frogs (Rana pipiens): laboratory and field evidence. Environ Health Perspect 111:568-575.
  9. Iida H, Maehara K, Doiguchi M, Mori T, Yamada F (2003) Bisphenol A-induced apoptosis of cultured rat Sertoli cells. Reprod Toxicol 17:457-464. https://doi.org/10.1016/S0890-6238(03)00034-0
  10. Inoue MH, Oliveira RS, Jr., Regitano JB, Tormena CA, Constantin J, Tornisielo VL (2006) Sorption-desorption of atrazine and diuron in soils from southern Brazil. J Environ Sci Health B 41:605-621. https://doi.org/10.1080/03601230600701767
  11. Kim SK, Lee HJ, Yang H, Kim HS, Yoon YD (2004) Prepubertal exposure to 4-tert-octylphenol induces apoptosis of testicular germ cells in adult rat. Arch Androl 50:427-441. https://doi.org/10.1080/01485010490475093
  12. Laws SC, Ferrell JM, Stoker TE, Cooper RL (2003) Pubertal development in female Wistar rats following exposure to propazine and atrazine biotransformation by-products, diamino-S-chlorotriazine and hydroxyatrazine. Toxicol Sci 76:190-200. https://doi.org/10.1093/toxsci/kfg223
  13. Laws SC, Ferrell JM, Stoker TE, Schmid J, Cooper RL (2000) The effects of atrazine on female wistar rats: an evaluation of the protocol for assessing pubertal development and thyroid function. Toxicol Sci 58:366-376. https://doi.org/10.1093/toxsci/58.2.366
  14. Orton F, Carr JA, Handy RD (2006) Effects of nitrate and atrazine on larval development and sexual differentiation in the northern leopard frog Rana pipiens. Environ Toxicol Chem 25:65-71. https://doi.org/10.1897/05-136R.1
  15. Orton F, Lutz I, Kloas W, Routledge EJ (2009) Endocrine disrupting effects of herbicides and pentachlorophenol: in vitro and in vivo evidence. Environ Sci Technol 43:2144-2150. https://doi.org/10.1021/es8028928
  16. Sanderson JT, Letcher RJ, Heneweer M, Giesy JP, van den Berg M (2001) Effects of chloro-s-triazine herbicides and metabolites on aromatase activity in various human cell lines and on vitellogenin production in male carp hepatocytes. Environ Health Perspect 109:1027-1031. https://doi.org/10.1289/ehp.011091027
  17. Sanderson JT, Seinen W, Giesy JP, van den Berg M (2000) 2-Chloro-s-triazine herbicides induce aromatase (CYP19) activity in H295R human adrenocortical carcinoma cells: a novel mechanism for estrogenicity? Toxicol Sci 54:121-127. https://doi.org/10.1093/toxsci/54.1.121
  18. Stoker TE, Robinette CL, Cooper RL (1999) Maternal exposure to atrazine during lactation suppresses sucklinginduced prolactin release and results in prostatitis in the adult offspring. Toxicol Sci 52:68-79. https://doi.org/10.1093/toxsci/52.1.68
  19. Thibaut R, Porte C (2004) Effects of endocrine disrupters on sex steroid synthesis and metabolism pathways in fish. J Steroid Biochem Mol Biol 92:485-494. https://doi.org/10.1016/j.jsbmb.2004.10.008
  20. Tierney D, Clarkson JR, Christensen BR (1998) Exposure to the herbicides atrazine and simazine in drinking water. In: Ballantine L, McFarland JE, Hackett DS, editors. Triazine Herbicide Risk Assessment. Washington, DC: Oxford University Press.
  21. Wang X, Han X, Hou Y, Yao G, Wang Y (2003) Effect of nonylphenol on apoptosis of Sertoli cells in vitro. Bull Environ Contam Toxicol 70:898-904. https://doi.org/10.1007/s00128-003-0067-4