Development and Reproduction (한국발생생물학회지:발생과생식)

The Korean Society of Developmental Biology (한국발생생물학회)
권호 표지
DOI QR코드

DOI QR Code

Nonmonotonic Effects of Chronic Low-Dose Di(2-ethylhexyl) Phthalate on Gonadal Weight and Reproduction

  • Cha, Sunyeong (Division of Developmental Biology and Physiology, School of Biological Sciences and Chemistry, Sungshin University) ;
  • Jung, Kayeon (Division of Developmental Biology and Physiology, School of Biological Sciences and Chemistry, Sungshin University) ;
  • Lee, Min Young (Division of Developmental Biology and Physiology, School of Biological Sciences and Chemistry, Sungshin University) ;
  • Hwang, Yeon Jeong (Division of Developmental Biology and Physiology, School of Biological Sciences and Chemistry, Sungshin University) ;
  • Yang, Eunhyeok (Division of Developmental Biology and Physiology, School of Biological Sciences and Chemistry, Sungshin University) ;
  • Lee, Sung-Ho (Dept. of Lifesicence, Sangmyung University) ;
  • Jung, Hyo-il (School of Mechanical Engineering, Yonsei University) ;
  • Cheon, Yong-Pil (Division of Developmental Biology and Physiology, School of Biological Sciences and Chemistry, Sungshin University)
  • Received : 2018.02.07
  • Accepted : 2018.03.26
  • Published : 2018.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Endocrine disruptors have been concerned in toxicology but now challenged as physiological point especially concerned with exposing dose and period. In this study the low-dose chronic administration of di(2-ethylhexyl) phthaltae (DEHP) during reproductive period was examined to evaluate the possible roles. Adult male and female CD-1 mice were exposed to DEHP with drinking water containing $133{\mu}g/L$ and $1,330{\mu}g/L$ DEHP in water according to OECD 433 guide line and sacrificed just after weaning. The weights of uterus and ovary were decreased by drinking of $1,330{\mu}g/L$ DEHP water. There was not adverse effects on either accumulated mating rate and mating rate depend on estrus stage, pregnancy duration, and sex ration at birth. However, the accumulated rate of successful delivery and litter size were significantly high at $1,330{\mu}g/L$ DEHP water. The number of epididymal sperm was significantly increased by drinking of $1,330{\mu}g/L$ DEHP water. In addition, the number of follicles (primary, secondary, tertiary) were more many than control at $1,330{\mu}g/L$ DEHP water drunk mother. Though further studies are needed to identify what are the mechanism of DEHP in folliculogenesis and spermatogenesis. From this study we firstly report the effect of low-dose chronic administration of DEHP with drinking could change the ovarian follicle population size and spermatogenesis rate. Put together, those finding is different from previous high-dose effects and suggest the physiological role of DEHP in gonads and uterus.

Keywords

References

  1. ACEIII (2013) America's Children and the Environment Third Edition. https://www.epa.gov/sites/production/files/2015-06/documents/ace3_2013.pdf.
  2. Akingbemi BT, Ge R, Klinefelter GR, Zirkin BR, Hardy MP (2004) Phthalate-induced Leydig cell hyperplasia is associated with multiple endocrine disturbances. Proc Natl Acad Sci USA 101:775-780. https://doi.org/10.1073/pnas.0305977101
  3. Aldyreva MV, Klimova TS, Iziumova AS, Timofeevskaia LA (1975) The effect of phthalate plasticizers on the generative function. Gig Tr Prof Zabol 19:25-29.
  4. Andrade AJM, Grande SW, Talsness CE, Gericke C, Grote K, Golombiewski A, Sterner-Kock A, Chahoud I (2006) A dose response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): Reproductive effects on adult male offspring rats. Toxicology 228:85-97. https://doi.org/10.1016/j.tox.2006.08.020
  5. Bizzari S, Openbert B, Iskikava Y (2000) Plasticizers. Chemical Economics Handbook. Palo Alto, CA, SRI International.
  6. Bloom MS, Whitcomb BW, Chen Z, Ye A, Kannan K, Louis GB (2015) Associations between urinary phthalate concentrations and semen quality parameters in a general population. Hum Reprod 30:2645-2657. https://doi.org/10.1093/humrep/dev219
  7. Blount BC, Milgram KE, Silva MJ, Malek NA, Reidy JA, Needham LL, Brock JW (2000) Quantitative detection of eight phthalate metabolites in human urine using HPLC-APCI-MS/MS. Anal Chem 72:4127-4137. https://doi.org/10.1021/ac000422r
  8. Borch J, Metzdorff SB, Vinggaard AM, Brokken L, Dalgaard M (2006) Mechanisms underlying the antiandrogenic effect of diethylhexyl phthalate in fetal testis. Toxicology 223:144-155. https://doi.org/10.1016/j.tox.2006.03.015
  9. Center for Devices and Radiological Health, US Food and Drug Administration (2001) http://www.fda.gov/cdrh/ost/dehp-pvc.pdf.
  10. Cha S, Baek JW, Ji HJ, Choi JH, Kim C, Lee MY, Hwang YJ, Yang E, Lee SH, Jung H, 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
  11. Christiansen S, Boberg J, Axelstad M, Dalgaard M, Vinggaard AM, Metzdorff SB, Hass U (2010) Low-dose perinatal exposure to di(2-ethylhexyl) phthalate induces anti-androgenic effects in male rats. Reprod Toxicol 30:313-321. https://doi.org/10.1016/j.reprotox.2010.04.005
  12. Davis BJ, Maronpot RR, Heindel JJ (1994) Di-(2-ethylhexyl) phthalate suppresses estradiol and ovulation in cycling rats. Toxicol Appl Pharmacol 128:216-223. https://doi.org/10.1006/taap.1994.1200
  13. Fan J, Traore K, Li W, Amri H, Huang H, Wu C, Chen H, Zirkin B. 2010. Molecular mechanisms mediating the effect of mono-(2-ethylhexyl) phthalate on hormonestimulated steroidogenesis in MA-10 mouse tumor Leydig cells. Endocrinology 151:3348-3362. https://doi.org/10.1210/en.2010-0010
  14. Ferguson KK, Loch-Caruso R, Meeker JD (2012) Exploration of oxidative stress and inflammatory markers in relation to urinary phthalate metabolites: NHANES 1999-2006. Environ Sci Technol 46:477-485. https://doi.org/10.1021/es202340b
  15. Foster PM (2006) Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters. Int J Androl 29:140-147. https://doi.org/10.1111/j.1365-2605.2005.00563.x
  16. Grande SW, Andrade AJM, Talsness CE, Grote K, Golombiewski A, Stemer-Kock A, Chahoud I (2007) A dose-response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): Reproductive effects on adult female offspring rats. Toxicology 229:114-122. https://doi.org/10.1016/j.tox.2006.10.005
  17. Gray TJB, Beamand JA (1984) Effect of some phthalate esters and other testicular toxins on primary cultrues of testicular cells. Food Chem Toxicol 22:123-131. https://doi.org/10.1016/0278-6915(84)90092-9
  18. Guida N, Laudati G, Galgani M, Santopaolo M, Montuori P, Triassi M, Renzo GI, Canzoniero Mt, Formisano L (2014) Hiiistone deacetylase 4 promotes ubiquitindependent porteasomal degradation of Sp3 in SH-SY5Y cells treated with di(2-ethylhexyl) phthalate (DEHP), determining neuronal death. Toxicol Appl Pharmacol 280:190-198. https://doi.org/10.1016/j.taap.2014.07.014
  19. Guo Y, Wu Q, Kannan K (2011) Phthalate metabolites in urine from China, and implications for human exposures. Environ Int 37:893-898. https://doi.org/10.1016/j.envint.2011.03.005
  20. Heindel JJ, Gulati DK, Mounce RC, Russell SR, Lamb JC IV (1989) Reproductive toxicity of three phthalic acid esters in a continuous breeding protocol. Toxicol Sci 12:508-518. https://doi.org/10.1093/toxsci/12.3.508
  21. Howdeshell KL, Furr J, Lambright CR, Rider CV, Wilson VS, Gray LE Jr (2007) Cumulative effects of dibutyl phthalate and diethylhexyl phthalate on male rat reproductive tract development: Altered fetal steroid hormones and genes. Toxicol Sci 99:190-202. https://doi.org/10.1093/toxsci/kfm069
  22. Jarfelt K, Dalgaard M, Hass U, Borch J, Jacobsen H, Ladefoged O (2005) Antiandrogenic effects in male rats perinatally exposed to a mixture of di(2-ethylhexyl) phthalate and di(2-ethylhexyl) adipate. Reprod Toxicol 19:505-515. https://doi.org/10.1016/j.reprotox.2004.11.005
  23. Kaul AF, Souney PF, Osathanondh R (1982) A review of possible toxicity of di-2-ethylhexylphthalate (DEHP) in plastic intravenous containers: Effects on reproduction. Drug Intell Clin Pharm 16:689-692. https://doi.org/10.1177/106002808201600908
  24. Kavlok R, Boekelheide K, Chapin R, Cunningham M, Faustman E, Foster P, Golub M, Henderson R, Hinberg I, Little R, seed J, Shea K, Tabacova S, Tyl R, Williams P, Zacharewski T (2002) NTP center for the evaluation of risks to human reproduction: phthalates expert panal reprot on the reproductive and developmental toicity of di(20dthylhexyl) phthatlate. Reprod Toxicol 16:529-653. https://doi.org/10.1016/S0890-6238(02)00032-1
  25. Kawaguchi S, Kuwahara R, Kohara Y, Uchida Y, Oku Y, Yamashita K (2015) Oral exposure to low-dose of nonylphenol impairs memory performance in Sprague-Dawley rats. J Toxicol Sci 40:43-53. https://doi.org/10.2131/jts.40.43
  26. Kyselova V, Peknicova J, Buckiova D, Boubelik M (2003) Effects of p-nonylphenol and resveratrol on body and organ weight and in vitro fertility of outbred CD-1 mice. Reprod Biol Endocrinol 1:30-39. https://doi.org/10.1186/1477-7827-1-30
  27. Latini G, De Felice C, Presta G, Del Vecchio A, Paris I, Ruggieri F, Mazzeo P (2003) In utero exposure to di-(2-ethylhexyl) phthalate and duration of human pregnancy. Environ Health Perspect 111:1783-1785. https://doi.org/10.1289/ehp.6202
  28. Li Y, Hu Y, Dong C, Lu H, Zhang C, Hu Q, Li S, Qin H, Li Z, Wang Y (2016) Vimentin-mediated steroidogenesis induced by phthalate esters: Involvement of DNA demethylation and nuclear factor kB. PLoS One 11, e0146138. https://doi.org/10.1371/journal.pone.0146138
  29. Liu L, Wang H, Tian M, Zhang J, Panuwet P, D'Souza PE, Barr DB, Huang Q, Xia Y, Shen H (2017) Phthalate metabolites related to infertile biomarkers and infertility in Chinese men. Environ Pollut 231:291-300. https://doi.org/10.1016/j.envpol.2017.08.018
  30. Lovekamp-Swan T, Davis BJ (2003) Mechanisms of phthalate ester toxicity in the female reproductive system. Environ Health Perspect 111:139-145.
  31. Niermann S, Rattan S, Brehm E, Flaws JA (2015) Prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP) affects reproductive outcomes in female mice. Reprod Toxicol 53:23-32. https://doi.org/10.1016/j.reprotox.2015.02.013
  32. Parks LG, Ostby JS, Lambright CR, Abbott BD, Klinefelter GR, Barlow JN, Gray LE Jr (2000) The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol Sci 58:339-349. https://doi.org/10.1093/toxsci/58.2.339
  33. Rhomberg LR, Goodman JE (2012) Low-dose effects and nonmonotonic dose-responses of endocrine disrupting chemicals: Has the case been made? Reg Toxicol Pharmacol 64:130-133. https://doi.org/10.1016/j.yrtph.2012.06.015
  34. Rybska M, Knap S, jankowski M, jeseta M, Bukowska D, Antosik P, Nowicki M, Zabel M, Kempisty B, Jaskowski JM (2018) Characteristic of factors influencing the proper course of folliclulogenesis in mammals. Med J Cell Biol 6:33-38. https://doi.org/10.2478/acb-2018-0006
  35. Savchuk I, Soder O, Svechnikov K (2015) Mono-2-ethylhexyl phthalate stimulates androgen production but suppresses mitochondrial function in mouse Leydig cells with different steroidogenic potential. Toxicol Sci 145:149-156. https://doi.org/10.1093/toxsci/kfv042
  36. Silva MJ, Barr DB, Reidy JA, Malek NA, Hodge CC, Caudill SP, Brock JW, Needham LL, Calafat AM (2004) Urinary levels of seven phthalate metabolites in the US population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000. Environ Health Perspect 112:331-338.
  37. Stroheker T, Cabaton N, Nourdin G, Regnier JF, Lhuguenot JC, Chagnon MC (2005) Evaluation of antiandrogenic activity of di-(2-ethylhexyl)phthalate. Toxicology 208:115-121. https://doi.org/10.1016/j.tox.2004.11.013
  38. Tomita I, Nakamura Y, Yagi Y, Tukikawa K (1986) Fetotoxic effects of mono-2-ethylhexyl phthalate (MEHP) in mice. Environ Health Perspect 65:249-254.
  39. Vandenberg LN, Colborn TC, Hayes TB, Heindel JJ, Jacobs DR, Lee DH, Shioda T, Soto AM, vom Saal FS, Welshons WV, Zoeller RT, Myers JP (2012) Hormones and endocrine-disrupting chemicals: Low-dose effects and nonmonotonic dose responses. Endocrine Reviews 33:378-455. https://doi.org/10.1210/er.2011-1050
  40. Weuve J, Hauser R, Calafat AM, Missmer A, Wise LA (2010) Association of exposure to phthalates with endometriosis and uterine leiomyomata: Findings from NHANES, 1999-2004. Environ Health Perspect 118: 825-832. https://doi.org/10.1289/ehp.0901543
  41. Wilson VS, Blystone CR, Hotchkiss AK, Rider CV, Gray LE (2008) Diverse mechanisms of antiandrogen action: Impact on male rat reproductive tract development. Int J Androl 31:178-187. https://doi.org/10.1111/j.1365-2605.2007.00861.x
  42. Xu Z, Liu J, Wu X, Huang B, Pan X (2017) Nonmonotonic responses to low doses of xenoestrogens: A review. Environ Res 155:199-207. https://doi.org/10.1016/j.envres.2017.02.018
  43. Zoeller Rt, Brown TR, Doan LL, Gore AC, Skakkebaek NE, Soto AM, Woodruff TJ, Saal FSV (2012) Endocrine-disrupting chemicals and public health protection: A statement of principles from the endocrine society. Endocrinology 153:4097-4110. https://doi.org/10.1210/en.2012-1422