Development and Reproduction (한국발생생물학회지:발생과생식)

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

DOI QR Code

Chronic and Low Dose Exposure to Nonlyphenol or Di(2-Ethylhexyl) Phthalate Alters Cell Proliferation and the Localization of Steroid Hormone Receptors in Uterine Endometria in Mice

  • Kim, Juhye (Division of Developmental Biology and Physiology, Dept. of Biotechnology, Sungshin University) ;
  • Cha, Sunyeong (Division of Developmental Biology and Physiology, Dept. of Biotechnology, Sungshin University) ;
  • Lee, Min Young (Division of Developmental Biology and Physiology, Dept. of Biotechnology, Sungshin University) ;
  • Hwang, Yeon Jeong (Division of Developmental Biology and Physiology, Dept. of Biotechnology, Sungshin University) ;
  • Yang, Eunhyeok (Division of Developmental Biology and Physiology, Dept. of Biotechnology, Sungshin University) ;
  • Choi, Donchan (Dept. of Life Science, College of Environmental Sciences, Yong-In University) ;
  • Lee, Sung-Ho (Dept. of Biotechnology, Sangmyung University) ;
  • Cheon, Yong-Pil (Division of Developmental Biology and Physiology, Dept. of Biotechnology, Sungshin University)
  • Received : 2019.06.08
  • Accepted : 2019.09.19
  • Published : 2019.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Based on our preliminary results, we examined the possible role of low-dose and chronic-exposing of the chemicals those are known as endocrine disrupting chemical (EDC), on the proliferation of uterine endometrium and the localization of steroid receptors. Immunohistochemical or immunofluorochemical methodology were employed to evaluate the localization of antigen identified by monoclonal antibody Ki 67 protein (MKI67), estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), and progesterone receptor (PGR). In $133{\mu}g/L$ and $1,330{\mu}g/L$ di(2-ethylhexyl) phthalate (DEHP) and $50{\mu}g/L$ nonylphenol (NP) groups, the ratio of MKI67 positive stromal cells was significantly increased but not in $500{\mu}g/L$ NP group. The ratios of MKI67 positive glandular and luminal epithelial cells were also changed by the chronic administration of NP and DEHP in tissue with dose specific manner. ESR1 signals were localized in nucleus in glandular and luminal epithelia of control group but its localization was mainly in cytoplasm in DEHP and NP administered groups. On the other hand, it was decreased at nucleus of stromal cells in $1,330{\mu}g/L$ DEHP group. The colocalization patterns of these nuclear receptors were also modified by the administration of these chemicals. Such a tissue specific and dose specific localization of ESR2 and PGR were detected as ESR1 in all the uterine endometrial tissues. These results show that the chronic lows-dose exposing of NP or DEHP modify the localization and colocalization of ESRs and PGR, and of the proliferation patterns of the endometrial tissues.

Keywords

References

  1. Bulun SE, Monsavais D, Pavone ME, Dyson M, Xue Q, Attar E, Tokunaga H, Su E (2012) Role of estrogen receptor-${\beta}$ in endometriosis. Semin Reprod Med 30:39-45. https://doi.org/10.1055/s-0031-1299596
  2. Cato AC, Heitlinger E, Ponta H, Klein-Hitpass L, Ryffel GU, Bailly A, Rauch C, Milgrom E (1988) Estrogen and progesterone receptor-binding sites on the chicken vitellogenin II gene: Synergism of steroid hormone action. Mol Cell Biol 8:5323-5330. https://doi.org/10.1128/MCB.8.12.5323
  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. Cha J, Sun X, Dey SK (2012) Mechanisms of implantation: Strategies for successful pregnancy. Nat Med 18:1754-1767. https://doi.org/10.1038/nm.3012
  5. Chung D, Gao F, Jegga AG, Das SK (2015) Estrogen mediated epithelial proliferation in the uterus is directed by stromal Fgf10 an Bmp8a. Mol Cell Endocrinol 400:48-60. https://doi.org/10.1016/j.mce.2014.11.002
  6. Cooke PS, Buchanan DL, Young P, Setiawan T, Brody J, Korach KS, Taylor J, Lubahn DB, Cunha GR (1997) Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium. Proc Natl Acad Sci USA 94:6535-6540. https://doi.org/10.1073/pnas.94.12.6535
  7. Danzo BJ, Shappell HW, Banerjee A, Hachey DL (2002) Effects of nonylphenol, 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (p,p'-DDE), and pentachlorophenol on the adult female guinea pig reproductive tract. Reprod Toxicol 16:29-43. https://doi.org/10.1016/S0890-6238(01)00194-0
  8. 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
  9. Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS, Toppari J, Zoeller RT (2015) EDC-2: the endocrine society's second scientific statement on endocrine-disrupting chemicals. Endocr Rev 36:E1-E150. https://doi.org/10.1210/er.2015-1010
  10. Grant-Tschudy KS, Wira CR (2005) Effect of oestradiol on mouse uterine epithelial cell tumour necrosis factor-$\alpha$ release is mediated through uterine stromal cells. Immunology 115:99-107. https://doi.org/10.1111/j.1365-2567.2005.02134.x
  11. Jobling S, Reynolds T, White R, Parker MG, Sumpter JP (1995) A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic. Environ Health Perspect 103:582-587. https://doi.org/10.1289/ehp.95103582
  12. Katzenellenbogen BS (1980) Dynamics of steroid hormone receptor action. Annu Rev Physiol 42:17-36. https://doi.org/10.1146/annurev.ph.42.030180.000313
  13. Kempisty B, Wojtanowicz-Markiewicz K, Ziolkowska A, Budna J, Ciesiolka S, Piotrowska H, Bryja A, Antosik P, Bukowska D, Wollenhaupt K, Bruska M, Brussow KP, Nowicki M, Zabel M (2015) Association between progesterone and estradiol-17beta treatment and protein expression of pgr and PGRMC1 in porcine luminal epithelial cells: A real-time cell proliferation approach. J Biol Regul Homeost Agents 29:39-50.
  14. Kim J, Cha S, Lee MY, Hwang YJ, Yang E, Ryou C, Jung HI, Cheon YP (2018) Chronic low-dose nonylphenol or di-(2-ethylhexyl) phthalate has a different estrogenlike response in mouse uterus. Dev Reprod 22:379-391. https://doi.org/10.12717/DR.2018.22.4.379
  15. Kim YB, Cheon YP, Lee SH (2019) Adverse effect of nonyphenol 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
  16. Korach KS (1994) Insights from the study of animals lacking functional estrogen receptor. Science 266:1524-1527. https://doi.org/10.1126/science.7985022
  17. Kurita T, Young P, Brody JR, Lydon JP, O/Malley BW, Cunha GR (1998) Stromal progesterone receptors mediate the inhibitory effects of progesterone on estrogeninduced uterine epithelial cell deoxyribonucleic acid synthesis. Endocrinology 139:4708-4713. https://doi.org/10.1210/endo.139.11.6317
  18. Lauber AH, Romano GJ, Mobbs CV, Pfaff DW (1990) Estradiol regulation of estrogen receptor messenger ribonucleic acid in rat mediobasal hypothalamus: An in situ hybridization study. J Neuroendocrinol 2:605-611. https://doi.org/10.1111/j.1365-2826.1990.tb00454.x
  19. Lee PC, Lee W (1996) In vivo estrogenic action of nonylphenol in immature female rats. Bull Environ Contam Toxicol 57:341-348. https://doi.org/10.1007/s001289900196
  20. Lorz PM, Towae FK, Enke W, Jackh R, Bhargava N, Hillesheim W (2012) Phthalic Acid and Derivatives. Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH Verlag, Weinheim, German.
  21. Lovekamp-Swan T, Davis B (2003) Mechanisms of phthalate ester toxicity in the female reproductive system. Environ Health Perspect 111:139-145. https://doi.org/10.1289/ehp.5658
  22. Lydon JP, DeMayo FJ, Funk CR, Mani SK, Hughes AR, Montgomery CA, Shyamala G, Conneely OM, O'Malley BW (1995) Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Genes Dev 9: 2266-2278. https://doi.org/10.1101/gad.9.18.2266
  23. Lydon JP, DeMayo FJ, Conneely OM, O'Malley B (1996) Reproductive phenotypes of the progesterone receptor null mutant mouse. J Steroid Biochem Mol Biol 56:67-77. https://doi.org/10.1016/0960-0760(95)00254-5
  24. Marcus GJ (1974) Mitosis in the rat uterus during the estrous cycle, early pregnancy, and early pseudopregnancy. Biol Reprod 10:447-452. https://doi.org/10.1095/biolreprod10.4.447
  25. Pawar S, Laws MJ, Bagchi IC, Bagchi MK (2015) Uterine epithelial estrogen receptor-${\alpha}$ controls decidualization via a paracrine mechanism. Mol Endocrinol 29:1362-1374. https://doi.org/10.1210/me.2015-1142
  26. Richardson KA, Hannon PR, Johnson-Walker YJ, Myint MS, Flaws JA, Nowak RA (2018). Di(2-ethylhexyl) phthalate (DEHP) alters proliferation and uterine gland numbers in the uteri of adult exposed mice. Reprod Toxicol 77:70-79. https://doi.org/10.1016/j.reprotox.2018.01.006
  27. Sa SI, Fonseca BM (2017) Dynamics of progesterone and estrogen receptor alpha in the ventromedial hypothalamus. J Endocrinol 233:197-207. https://doi.org/10.1530/JOE-16-0663
  28. Sa SI, Fonseca BM, Teixeira N, Madeira MD (2015) Estrogen receptors ${\alpha}$ and ${\beta}$ have different roles in the induction and trafficking of progesterone receptors in hypothalamic ventromedial neurons. FEBS Journal 282:1126-1136. https://doi.org/10.1111/febs.13207
  29. Scsukova S, Rollerova E, Mlynarcikova AB (2016) Impact of endocrine disrupting chemicals on onset and development of female reproductive disorders and hormonerelated cancer. Reprod Biol 16:243-254. https://doi.org/10.1016/j.repbio.2016.09.001
  30. Somasundaram DB, Manokaran K, Selvanesan BC, Bhaskaran RS (2016) Impact of di-(2-ethylhexyl) phthalate on the uterus of adult Wistar rats. Hum Exp Toxicol 36:565-572. https://doi.org/10.1177/0960327116657601
  31. Tibbetts TA, Mendoza-Meneses M, O'Malley BW, Conneely OM (1998) Mutual intercompartmental regulation of estrogen receptor and progesterone receptor expression in mouse uterus. Biol Reprod 59:1143-1152. https://doi.org/10.1095/biolreprod59.5.1143
  32. Tsai SJ, Wu MH, Chen HM, Chuang PC, Wing LYC (2002) Fibroblast growth factor-9 is an endometrial stromal growth factor. Endocrinology 143:2715-2721. https://doi.org/10.1210/endo.143.7.8900
  33. Weihua Z, Saji S, Makinen S, Cheng G, Jensen EV, Warner M, Gustafsson JA (2000) Estrogen receptor (ER) $\beta$, a modulator of $ER{\alpha}$ in the uterus. Proc Natl Acad Sci USA 97:5936-5941. https://doi.org/10.1073/pnas.97.11.5936
  34. Yilmaz BD, Bulun SE (2019) Endometriosis and nuclear receptors. Hum Reprod Update 25:473-485. https://doi.org/10.1093/humupd/dmz005
  35. Zhang W, Yang J, Wang J, Xia P, Xu Y, Jia H, Chen Y (2007) Comparative studies on the increase of uterine weight and related mechanisms of cadmium and pnonylphenol. Toxicology 241:84-91. https://doi.org/10.1016/j.tox.2007.08.089