Journal of Embryo Transfer (한국수정란이식학회지)

The Korean Society of Embryo Transfer (한국수정란이식학회)
권호 표지
DOI QR코드

DOI QR Code

Methoxychlor Produces Many Adverse Effects on Male Reproductive System, Kidney and Liver by Binding to Oestrogen Receptors

  • Kim, Dae Young (Department of Life Science, College of BioNano Technology, Gachon University)
  • Received : 2013.05.01
  • Accepted : 2013.05.26
  • Published : 2013.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Methoxychlor (MXC) was developed to be a replacement for the banned pesticide DDT. HPTE [2,2-bis (p-hydroxyphenyl)-1,1,1-trichloroethane], which is an in vivo metabolite of MXC, has strong oestrogenic and anti-androgenic effects. MXC and HPTE are thought to produce potentially adverse effects by acting through oestrogen and androgen receptors. Of the two, HPTE binds to sex-steroid receptors with greater affinity, and it inhibits testosterone biosynthesis in Leydig cells by inhibiting cholesterol side-chain cleavage enzyme activity and cholesterol utilisation. In a previous study, MXC was shown to induce Leydig cell apoptosis by decreasing testosterone concentrations. I focused on the effects of MXC on male mice that resulted from interactions with sex-steroid hormone receptors. Sex-steroid hormones affect other organs including the kidney and liver. Accordingly, I hypothesised that MXC can act through sex-steroid receptors to produce adverse effects on the testis, kidney and liver, and I designed our experiments to confirm the different effects of MXC exposure on the male reproductive system, kidney and liver. In these experiments, I used pre-pubescent ICR mice; the puberty period in ICR mice is from postnatal day (PND) 45 to PND60. I treated the experimental group with 0, 100, 200, 400 mg MXC/kg b.w. delivered by an intra-peritoneal injection with sesame oil used as vehicle for 4 weeks. At the end of the experiment, the mice were sacrificed under anaesthesia. The testes and accessory reproductive organs were collected, weighed and prepared for histological investigation. I performed a chemiluminescence immune assay to observe the serum levels of testosterone, LH and FSH. Blood biochemical determination was also performed to check for other effects. There were no significant differences in our histological observations or relative organ weights. Serum testosterone levels were decreased in a dose-dependent manner; a greater dose resulted in the production of less testosterone. Compared to the control group, testosterone concentrations differed in the 200 and 400 mg/kg dosage groups. In conclusion, I observed markedly negative effects of MXC exposure on testosterone concentrations in pre-pubescent male mice. From our biochemical determinations, I observed some changes that indicate renal and hepatic failure. Together, these data suggest that MXC produces adverse effects on the reproductive system, kidney and liver.

Keywords

References

  1. Akingbemi BT, Ge RS, Klinefelter GR, Gunsalus GL and Hardy MP. 2000. A metabolite of methoxychlor, 2,2-bis (p-hydroxyphenyl)-1,1,1-trichloroethane, reduces testosterone biosynthesis in rat leydig cells through suppression of steady-state messenger ribonucleic acid levels of the cholesterol side-chain cleavage enzyme. Biol. Reprod. 62(3): 571-578. https://doi.org/10.1095/biolreprod62.3.571
  2. Alworth LC, Howdeshell KL, Ruhlen RL, Day JK, Lubahn DB, Huang TH, Besch-Williford CL and vom Saal FS. 2002. Uterine responsiveness to estradiol and DNA methylation are altered by fetal exposure to diethystilbestrol and methoxychlor in CD-1 mice: effects of low versus high doses. Toxicol. Appl. Pharmacol. 183(1):10-22. https://doi.org/10.1006/taap.2002.9459
  3. Ashraf MS, Vongpatanasin W. 2006. Estrogen and hypertension. Curr. Hypertens. Rep. 8(5):368-376. https://doi.org/10.1007/s11906-006-0080-1
  4. Bagur AC and Mautalen CA. 1992. Risk for developing osteoporosis in untreated premature menopause. Calcif. Tissue Int. 51(1):4-7. https://doi.org/10.1007/BF00296207
  5. Bulger WH, Muccitelli RM and Kupfer D. 1978. Interactions of methoxychlor, methoxychlor base-soluble contaminant, and 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane with rat uterine estrogen receptor. J. Toxicol. Environ. Health 4 (5-6):881-893. https://doi.org/10.1080/15287397809529709
  6. Carlsen E, Giwercman A, Keiding N and Skakkebaek NE. 1992. Evidence for decreasing quality of semen during past 50 years. BMJ. 305(6854):609-613. https://doi.org/10.1136/bmj.305.6854.609
  7. Cooke PS and Eroschenko VP. 1990. Inhibitory effects of technical grade methoxychlor on development of neonatal male mouse reproductive organs. Biol. Reprod. 42(3):585-596. https://doi.org/10.1095/biolreprod42.3.585
  8. Crisp TM, Clegg ED, Cooper RL, Wood WP, Anderson DG, Baetcke KP, Hoffmann JL, Morrow MS, Rodier DJ, Schaeffer JE, Touart LW, Zeeman MG and Patel YM. 1998. Environmental endocrine disruption: an effects assessment and analysis. Environ. Health Perspect. 106(1):11-56.
  9. Cummings AM and Laskey J. 1993. Effect of methoxychlor on ovarian steroidogenesis: role in early pregnancy loss. Reprod. Toxicol. 7(1):17-23.
  10. Cummings AM. 1997. Methoxychlor as a model for environmental estrogens. Critical Reviews in Toxicology 27: 367-379. https://doi.org/10.3109/10408449709089899
  11. Gast, GC, Grobbee, DE, Pop VJ, Keyzer JJ, Wijnands-van Gent CJ, Samsioe GN, Nilsson PM and van der Schouw YT. 2008. Menopausal complaints are associated with cardiovascular risk factors. Hypertension 51(6):1492-1498. https://doi.org/10.1161/HYPERTENSIONAHA.107.106526
  12. Goldman JM, Cooper RL, Rehnberg GL, Hein JF, McElroy WK and Gray LE. 1986. Effects of low subchronic doses of methoxychlor on the hypothalamic-pituitary reproductive axis. Toxicol. Appl. Pharmacol. 86:474-83. https://doi.org/10.1016/0041-008X(86)90375-3
  13. Gray LE Jr, Ostby J, Cooper RL and Kelce WR. 1999. The estrogenic and antiandrogenic pesticide methoxychlor alters the reproductive tract and behavior without affecting pituitary size or LH and prolactin secretion in male rats. Toxicol. Ind. Health 15(1-2):37-47.
  14. Kapoor IP, Metcalf RL, Nystrom RF and Sangha GK. 1970. Comparative metabolism of methoxychlor, methiochlor, and DDT in mouse, insects, and in a model ecosystem. J. Agric. Food Chem. 18(6):1145-1152. https://doi.org/10.1021/jf60172a017
  15. Lane PH. 2008. Estrogen receptors in the kidney: Lessons from genetically altered mice. Gend. Med., Suppl. A. 5: S11-18. https://doi.org/10.1016/j.genm.2008.03.003
  16. Linder RE, Strader LF, Slott VL and Suarez JD. 1992. Endpoints of spermatotoxicity in the rat after short duration exposures to fourteen reproductive toxicants. Reprod. Toxicol. 6(6):491-505. https://doi.org/10.1016/0890-6238(92)90034-Q
  17. Murono EP and Derk RC. 2004. The effects of the reported active metabolite of methoxychlor, 2,2-bis (p-hydroxyphenyl)- 1,1,1-trichloroethane, on testosterone formation by cultured Leydig cells from young adult rats. Reprod. Toxicol. 19(1):135-146. https://doi.org/10.1016/j.reprotox.2004.06.010
  18. Reuber MD. 1980. Carcinogenicity and toxicity of methoxychlor. Environ. Health Perspect. 36:205-219. https://doi.org/10.1289/ehp.8036205
  19. Tyl RW, Myers CB, Marr MC, Sloan CS, Castillo NP, Veselica MM, Seely JC, Dimond SS, Van Miller JP, Shiotsuka RN, Beyer D, Hentges SG and Waechter JM Jr. 2008. Twogeneration reproductive toxicity study of dietary bisphenol A in CD-1 (Swiss) mice. Toxicol. Sci. 104(2):362-384.