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Adverse Effect of Nonylphenol on the Reproductive System in F2 Male Mice : A Qualitative Change?

  • Kim, Yong-Bin (Dept. of Biotechnology, Sangmyung University) ;
  • Cheon, Yong-Pil (Division of Developmental Biology and Physiology, Dept. of Lifetechnology, Sungshin University) ;
  • Choi, Donchan (Dept. of Life Science, College of Environmental Sciences, Yong-In University) ;
  • Lee, Sung-Ho (Dept. of Biotechnology, Sangmyung University)
  • Received : 2019.07.14
  • Accepted : 2019.09.05
  • Published : 2019.09.30

Abstract

Previously, we reported negative effects of low-dose nonylphenol (NP) exposure on the reproductive organs of F1 male mice. In the present study was further investigated the endocrine disrupting effect of NP exposure to F2 generation male mice. Mice were divided into 2 groups; (1) CON, control animals and (2) NP-50 ($50{\mu}g/L$), animals were treated with NP via drinking water. NP exposures were continuously conducted from parental pre-mating period until the postnatal day (PND) 55 of F2 offsprings. Mice were sacrificed on PND 55 and the reproductive tissue weights were measured. The initial (at PND 21) and terminal (PND 55) body weights of the NP-50 group animals were not significantly different from those of control group animals. NP exposure fail to induce a significant weight change of the testes, seminal vesicle and prostate except absolute epididymal weight (p<0.05). However, pathohistological studies revealed that NP-treated F2 animals showed evident decrease in seminiferous tubule diameters, reduced luminal area and number of germ cells. Also, sloughing morphologies in the tubules were notable. In the caudal epididymis, fewer mature sperms and swollen epithelial cells were found in the NP-treated group. The present study demonstrated that the subchronic low-dose NP exposure induced pathohistological abnormalities in testis and epididymis of F2 mice, and we assumed that these 'qualitative' changes in reproductive tissues could be derived from the epigenetic modifications such as DNA methylation, histone modification, altered DNA accessibility and chromatin structure. Further studies are needed to achieve a better understanding on the multi- or trans-generational effects of NP on the reproductive health and a human application.

Keywords

References

  1. Aly HA, Domenech O, Banjar ZM (2012) Effect of nonylphenol on male reproduction: Analysis of rat epididymal biochemical markers and antioxidant defense enzymes. Toxicol Appl Pharmacol 261:134-141. https://doi.org/10.1016/j.taap.2012.02.015
  2. Anway MD, Memon MA, Uzumcu M, Skinner MK (2006) Transgenerational effect of the endocrine disruptor vinclozolin on male spermatogenesis. J Androl 27:868-879. https://doi.org/10.2164/jandrol.106.000349
  3. Cha S, Baek JW, Ji HJ, Choi JH, Kim C, Lee MY, Hwang YJ, Yang E, Lee SH, Jung HI, Cheon YP (2017) Disturbing effects of chronic low-dose 4-nonylphenol exposing on gonadal weight and reproductive outcome over one-generation. Dev Reprod 21:121-130. https://doi.org/10.12717/DR.2017.21.2.121
  4. Chapin RE, Delaney J, Wang Y, Lanning L, Davis B, Collins B, Mintz N, Wolfe G (1999) The effects of 4-nonylphenol in rats: A multigeneration reproduction study. Toxicol Sci 52:80-91. https://doi.org/10.1093/toxsci/52.1.80
  5. Chitra KC, Latchoumycandane C, Mathur PP (2002) Effect of nonylphenol on the antioxidant system in epididymal sperm of rats. Arch Toxicol 76:545-551. https://doi.org/10.1007/s00204-002-0372-4
  6. Di QN, Cao WX, Xu R, Lu L, Xu Q, Wang XB (2018) Chronic low-dose exposure of nonylphenol alters energy homeostasis in the reproductive system of female rats. Toxicol Appl Pharmacol 348:67-75. https://doi.org/10.1016/j.taap.2018.04.007
  7. Doyle TJ, Bowman JL, Windell VL, McLean DJ, Kim KH (2013) Transgenerational effects of di-(2-ethylhexyl) phthalate on testicular germ cell associations and spermatogonial stem cells in mice. Biol Reprod 88:112. https://doi.org/10.1095/biolreprod.112.106104
  8. Duan P, Hu C, Butler HJ, Quan C, Chen W, Huang W, Tang S, Zhou W, Yuan M, Shi Y, Martin FL, Yang K (2016) Effects of 4-nonylphenol on spermatogenesis and induction of testicular apoptosis through oxidative stress-related pathways. Reprod Toxicol 62:27-38. https://doi.org/10.1016/j.reprotox.2016.04.016
  9. Gong Y, Wu J, Huang Y, Shen S, Han X (2009) Nonylphenol induces apoptosis in rat testicular Sertoli cells via endoplasmic reticulum stress. Toxicol Lett 186:84-95. https://doi.org/10.1016/j.toxlet.2009.01.010
  10. Guenther K, Heinke V, Thiele B, Kleist E, Prast H, Raecker T (2002) Endocrine disrupting nonylphenols are ubiquitous in food. Environ Sci Technol 36:1676-1780. https://doi.org/10.1021/es010199v
  11. Guerrero-Bosagna CM, Skinner MK (2009) Epigenetic transgenerational effects of endocrine disruptors on male reproduction. Semin Reprod Med 27:403-408. https://doi.org/10.1055/s-0029-1237428
  12. Han XD, Tu ZG, Gong Y, Shen SN, Wang XY, Kang LN, Hou YY, Chen JX (2004) The toxic effects of nonylphenol on the reproductive system of male rats. Reprod Toxicol 19:215-221. https://doi.org/10.1016/j.reprotox.2004.06.014
  13. Hu Y, Wang R, Xiang Z, Qian W, Han X, Li D (2014) Antagonistic effects of a mixture of low-dose nonylphenol and di-n-butyl phthalate (monobutyl phthalate) on the Sertoli cells and serum reproductive hormones in prepubertal male rats in vitro and in vivo. PLOS ONE 9:e93425. https://doi.org/10.1371/journal.pone.0093425
  14. Kim YB, Cheon YP, Lee S-H (2019) Adverse effect of nonylphenol on the reproductive system in F1 male mice: A subchronic low-dose exposure model. Dev Reprod 23:93-99. https://doi.org/10.12717/DR.2019.23.2.093
  15. Kyselova V, Peknicova J, Buckiova D, Boubelik M (2003) Effects of p-nonylphenol and resveratrol on body and organ weight and in vivo fertility of outbred CD-1 mice. Reprod Biol Endocrinol 1:30. https://doi.org/10.1186/1477-7827-1-30
  16. Lee DH (2018) Evidence of the possible harm of endocrine-disrupting chemicals in humans: Ongoing debates and key issues. Endocrinol Metab 33:44-52. https://doi.org/10.3803/EnM.2018.33.1.44
  17. Lu YY, Chen ML, Sung FC, Wang PS, Mao IF (2007) Daily intake of 4-nonylphenol in Taiwanese. Environ Int 33:903-910. https://doi.org/10.1016/j.envint.2007.04.008
  18. Lu WC, Wang AQ, Chen XL, Yang G, Lin Y, Chen YO, Hong CJ, Tian HL (2014) 90d exposure to nonylphenol has adverse effects on the spermatogenesis and sperm maturation of adult male rats. Biomed Environ Sci 27:907-911. https://doi.org/10.3967/bes2014.128
  19. Martina CA, Weiss B, Swan SH (2012) Lifestyle behaviors associated with exposures to endocrine disruptors. Neurotoxicology 33:1427-1433. https://doi.org/10.1016/j.neuro.2012.05.016
  20. Mehranjani MS, Noorafshan A, Momeni HR, Abnosi MH, Mahmoodi M, Anvari M, Hoseini SM (2009) Stereological study of the effects of vitamin E on testis structure in rats treated with para-nonylphenol. Asian J Androl 11:508-516. https://doi.org/10.1038/aja.2009.29
  21. Nagao T, Saito Y, Usumi K, Nakagomi M, Yoshimura S, Ono H. (2000) Disruption of the reproductive system and reproductive performance by administration of nonylphenol to newborn rats. Hum Exp Toxicol 19:284-296. https://doi.org/10.1191/096032700678815909
  22. Nagao T, Wada K, Marumo H, Yoshimura S, Ono H (2001) Reproductive effects of nonylphenol in rats after gavage administration: A two-generation study. Reprod Toxicol 15:293-315. https://doi.org/10.1016/S0890-6238(01)00123-X
  23. Newbold RR, Hanson RB, Jefferson WN, Bullock BC, Haseman J, McLachlan JA (2000) Proliferative lesions and reproductive tract tumors in male descendants of mice exposed developmentally to diethylstilbestrol. Carcinogenesis 21:1355-1363. https://doi.org/10.1093/carcin/21.7.1355
  24. Noorimotlagh Z, Haghighi NJ, Ahmadimoghadam M, Rahim F (2017) An updated systematic review on the possible effect of nonylphenol on male fertility. Environ Sci Pollut Res Int 24:3298-3314. https://doi.org/10.1007/s11356-016-7960-y
  25. Rattan S, Brehm E, Gao L, Niermann S, Flaws JA (2018) Prenatal exposure to di (2-ethylhexyl) phthalate disrupts ovarian function in a transgenerational manner in female mice. Biol Reprod 98:130-145. https://doi.org/10.1093/biolre/iox154
  26. Sato T, Saito H, Uchiyama T, Fujimoto Y, Katase T, Kai O (2009) Effects of synthetic para-nonylphenol isomers administered chronically throughout pregnancy and lactation on reproductive system of mouse pups. Arch Toxicol 83:1097-1108. https://doi.org/10.1007/s00204-009-0464-5
  27. 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
  28. Soto AM, Justicia H, Wray JW, Sonnenschein C (1991) p-Nonyl-phenol: An estrogenic xenobiotic released from "modified" polystyrene. Environ Health Perspect 92:167-173. https://doi.org/10.1289/ehp.9192167
  29. Stouder C, Paoloni-Giacobino A (2011) Specific transgenerational imprinting effects of the endocrine disruptor methoxychlor on male gametes. Reproduction 141:207-216. https://doi.org/10.1530/REP-10-0400
  30. Tyl RW, Myers CB, Marr MC, Castillo NP, Seely JC, Sloan CS, Veselica MM, Joiner RL, Van Miller JP, Simon GS (2006) Three-generation evaluation of dietary para-nonylphenol in CD (Sprague-Dawley) rats. Toxicol Sci 92:295-310. https://doi.org/10.1093/toxsci/kfj203
  31. Uguz C, Varisli O, Agca C, Agca Y (2009) Effects of nonylphenol on motility and subcellular elements of epididymal rat sperm. Reprod Toxicol 28:542-549. https://doi.org/10.1016/j.reprotox.2009.06.007
  32. Uguz C, Varisli O, Agca C, Evans T, Agca Y (2015) In vitro effects of nonylphenol on motility, mitochondrial, acrosomal and chromatin integrity of ram and boar spermatozoa. Andrologia 47:910-919. https://doi.org/10.1111/and.12346
  33. Walker DM, Gore AC (2011) Transgenerational neuroendocrine disruption of reproduction. Nat Rev Endocrinol 7:197-207. https://doi.org/10.1038/nrendo.2010.215
  34. Xin F, Susiarjo M, Bartolomei MS (2015) Multigenerational and transgenerational effects of endocrine disrupting chemicals: A role for altered epigenetic regulation? Semin Cell Dev Biol 43:66-75. https://doi.org/10.1016/j.semcdb.2015.05.008