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Hormones and Cancer

, Volume 8, Issue 2, pp 78–89 | Cite as

Perinatal Exposure to Bisphenol A or Diethylstilbestrol Increases the Susceptibility to Develop Mammary Gland Lesions After Estrogen Replacement Therapy in Middle-Aged Rats

  • Ayelen L. Gomez
  • Melisa B. Delconte
  • Gabriela A. Altamirano
  • Lucia Vigezzi
  • Veronica L. Bosquiazzo
  • Luís F. Barbisan
  • Jorge G. Ramos
  • Enrique H. Luque
  • Mónica Muñoz-de-Toro
  • Laura KassEmail author
Original Paper

Abstract

The development of the mammary gland is a hormone-regulated event. Several factors can dysregulate its growth and make the gland more susceptible to cellular transformation. Among these factors, perinatal exposure to xenoestrogens and hormone replacement therapy has been associated with increased risk of developing breast cancer. Here, we assessed the effects induced by estrogen replacement therapy (ERT) in ovariectomized (OVX) middle-aged rats and whether perinatal exposure to diethylstilbestrol (DES) or bisphenol A (BPA) modified these effects in the mammary gland. Pregnant rats were orally exposed to vehicle, 5 μg DES/kg/day, or 0.5 or 50 μg BPA/kg/day from gestational day 9 until weaning. Then, 12-month-old offspring were OVX and treated with 17β-estradiol for 3 months. Morphological changes and the percentage of epithelial cells that proliferated or expressed estrogen receptor alpha (ESR1) and progesterone receptor (PR) were analyzed in mammary gland samples of 15-month-old animals. ERT induced lobuloalveolar hyperplasia and ductal cysts in the mammary gland of middle-aged rats, associated with a higher proliferation index of epithelial cells. Perinatal exposure to DES followed by ERT increased the number of cysts and induced the formation of fibroadenoma and ductal carcinoma in situ, without modifying the expression of ESR1 or PR. Also, after 3 months of ERT, BPA-exposed rats had a higher incidence of ductal hyperplasia and atypical lobular hyperplasia than animals under ERT alone. In conclusion, perinatal exposure to xenoestrogens increases the susceptibility of the mammary gland to develop cysts and hyperplastic lesions when confronted with ERT later in life.

Keywords

Mammary gland Bisphenol A Diethylstilbestrol Estrogen replacement therapy Endocrine disruptor 

Notes

Acknowledgments

We thank Juan Grant and Juan C. Villarreal (UNL) for their technical assistance and animal care.

G.A.A. and L.V. are fellows, and V.L.B., J.G.R., E.H.L., and L.K. are career investigators of CONICET.

Compliance with Ethical Standards

All procedures performed in studies involving animals were in accordance with the ethical standards of the Ethical Committee of the Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.

Conflict of Interest

The authors declare that they have no conflict of interest.

Financial Support

This work was supported by grants from Universidad Nacional del Litoral (CAI+D program #5120110100023LI), Consejo Nacional de Investigaciones Científicas y Técnicas (PIP#11220110100494), and Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT, PICT 2014 #1348), Argentina. These funding sources were not involved in the study design, sample collection, analysis or interpretation of the data, the writing of the report, or the decision to submit the article for publication.

References

  1. 1.
    Vandenberg LN, Ehrlich S, Belcher SM, Ben-Jonathan N, Dolinoy DC, Hugo ER, Hunt PA, Newbold RR, Rubin BS, Saili KS et al (2013) Low dose effects of bisphenol a. Endocrine Disruptors 1(1):e26490. doi: 10.4161/endo.26490 CrossRefGoogle Scholar
  2. 2.
    Seachrist DD, Bonk KW, Ho SM, Prins GS, Soto AM, Keri RA (2015) A review of the carcinogenic potential of bisphenol a. Reprod Toxicol 59:167–182. doi: 10.1016/j.reprotox.2015.09.006 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Soto AM, Sonnenschein C (2015) Endocrine disruptors: DDT, endocrine disruption and breast cancer. Nature Rev Endocrinology 11(9):507–508. doi: 10.1038/nrendo.2015.125 Google Scholar
  4. 4.
    Cohn BA, La Merrill M, Krigbaum NY, Yeh G, Park JS, Zimmermann L, Cirillo PM (2015) DDT exposure in utero and breast cancer. J Clin Endocrinol Metab 100(8):2865–2872. doi: 10.1210/jc.2015-1841 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Rudel RA, Fenton SE, Ackerman JM, Euling SY, Makris SL (2011) Environmental exposures and mammary gland development: state of the science, public health implications, and research recommendations. Environ Health Perspect 119(8):1053–1061. doi: 10.1289/ehp.1002864 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Fenton SE, Reed C, Newbold RR (2012) Perinatal environmental exposures affect mammary development, function, and cancer risk in adulthood. Annu Rev Pharmacol Toxicol 52:455–479. doi: 10.1146/annurev-pharmtox-010611-134659 CrossRefPubMedGoogle Scholar
  7. 7.
    Macon MB, Fenton SE (2013) Endocrine disruptors and the breast: early life effects and later life disease. J Mammary Gland Biol Neoplasia 18(1):43–61. doi: 10.1007/s10911-013-9275-7 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Gray JM, Maffini MV (2015) Give prevention a chance: reducing environmental exposures to improve breast health. Breast Diseases: A Year Book Quarterly 26(3):197–202. doi: 10.1016/j.breastdis.2015.07.038 Google Scholar
  9. 9.
    Vandenberg LN, Maffini MV, Sonnenschein C, Rubin BS, Soto AM (2009) Bisphenol-a and the great divide: a review of controversies in the field of endocrine disruption. Endocr Rev 30(1):75–95. doi: 10.1210/er.2008-0021 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Soto AM, Brisken C, Schaeberle C, Sonnenschein C (2013) Does cancer start in the womb? Altered mammary gland development and predisposition to breast cancer due to in utero exposure to endocrine disruptors. J Mammary Gland Biol Neoplasia 18(2):199–208. doi: 10.1007/s10911-013-9293-5 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Richter CA, Birnbaum LS, Farabollini F, Newbold RR, Rubin BS, Talsness CE, Vandenbergh JG, Walser-Kuntz DR, vom Saal FS (2007) In vivo effects of bisphenol a in laboratory rodent studies. Reprod Toxicol 24(2):199–224. doi: 10.1016/j.reprotox.2007.06.004 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Acevedo N, Davis B, Schaeberle CM, Sonnenschein C, Soto AM (2013) Perinatally administered bisphenol a as a potential mammary gland carcinogen in rats. Environ Health Perspect 121(9):1040–1046. doi: 10.1289/ehp.1306734 PubMedPubMedCentralGoogle Scholar
  13. 13.
    Durando M, Kass L, Piva J, Sonnenschein C, Soto AM, Luque EH, Muñoz-de-Toro MM (2007) Prenatal bisphenol a exposure induces preneoplastic lesions in the mammary gland in Wistar rats. Environ Health Perspect 115(1):80–86. doi: 10.1289/ehp.9282 CrossRefPubMedGoogle Scholar
  14. 14.
    Moral R, Wang R, Russo IH, Lamartiniere CA, Pereira J, Russo J (2008) Effect of prenatal exposure to the endocrine disruptor bisphenol a on mammary gland morphology and gene expression signature. J Endocrinol 196(1):101–112. doi: 10.1677/JOE-07-0056 CrossRefPubMedGoogle Scholar
  15. 15.
    Muñoz-de-Toro M, Markey CM, Wadia PR, Luque EH, Rubin BS, Sonnenschein C, Soto AM (2005) Perinatal exposure to bisphenol-a alters peripubertal mammary gland development in mice. Endocrinology 146(9):4138–4147. doi: 10.1210/en.2005-0340 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Paulose T, Speroni L, Sonnenschein C, Soto AM (2015) Estrogens in the wrong place at the wrong time: fetal BPA exposure and mammary cancer. Reprod Toxicol 54:58–65. doi: 10.1016/j.reprotox.2014.09.012 CrossRefPubMedGoogle Scholar
  17. 17.
    Rochester JR (2013) Bisphenol a and human health: a review of the literature. Reprod Toxicol 42:132–155. doi: 10.1016/j.reprotox.2013.08.008 CrossRefPubMedGoogle Scholar
  18. 18.
    Tharp AP, Maffini MV, Hunt PA, VandeVoort CA, Sonnenschein C, Soto AM (2012) Bisphenol a alters the development of the rhesus monkey mammary gland. Proc Natl Acad Sci U S A 109(21):8190–8195. doi: 10.1073/pnas.1120488109 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Delclos KB, Camacho L, Lewis SM, Vanlandingham MM, Latendresse JR, Olson GR, Davis KJ, Patton RE, Gamboa da Costa G, Woodling KA et al (2014) Toxicity evaluation of bisphenol a administered by gavage to Sprague Dawley rats from gestation day 6 through postnatal day 90. Toxicol Sci 139(1):174–197. doi: 10.1093/toxsci/kfu022 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Hilakivi-Clarke L (2014) Maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters. Breast Cancer Res 16(2):208. doi: 10.1186/bcr3649 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Swan SH (2000) Intrauterine exposure to diethylstilbestrol: long-term effects in humans. APMIS 108(12):793–804. doi: 10.1111/j.1600-0463.2000.tb00001.x CrossRefPubMedGoogle Scholar
  22. 22.
    Palmer JR, Wise LA, Hatch EE, Troisi R, Titus-Ernstoff L, Strohsnitter W, Kaufman R, Herbst AL, Noller KL, Hyer M et al (2006) Prenatal diethylstilbestrol exposure and risk of breast cancer. Cancer Epidemiol Biomark Prev 15(8):1509–1514. doi: 10.1158/1055-9965.EPI-06-0109 CrossRefGoogle Scholar
  23. 23.
    Hovey RC, Asai-Sato M, Warri A, Terry-Koroma B, Colyn N, Ginsburg E, Vonderhaar BK (2005) Effects of neonatal exposure to diethylstilbestrol, tamoxifen, and toremifene on the BALB/c mouse mammary gland. Biol Reprod 72(2):423–435. doi: 10.1095/biolreprod.104.029769 CrossRefPubMedGoogle Scholar
  24. 24.
    Sassarini J, Lumsden MA (2015) Oestrogen replacement in postmenopausal women. Age Ageing 44(4):551–558. doi: 10.1093/ageing/afv069 CrossRefPubMedGoogle Scholar
  25. 25.
    MacMahon B, Cole P, Brown J (1973) Etiology of human breast cancer: a review. J Natl Cancer Inst 50(1):21–42. doi: 10.1093/jnci/50.1.21 CrossRefPubMedGoogle Scholar
  26. 26.
    Raafat AM, Hofseth LJ, Li S, Bennett JM, Haslam SZ (1999) A mouse model to study the effects of hormone replacement therapy on normal mammary gland during menopause: enhanced proliferative response to estrogen in late postmenopausal mice. Endocrinology 140(6):2570–2580. doi: 10.1210/endo.140.6.6634 PubMedGoogle Scholar
  27. 27.
    Haslam SZ, Osuch JR, Raafat AM, Hofseth LJ (2002) Postmenopausal hormone replacement therapy: effects on normal mammary gland in humans and in a mouse postmenopausal model. J Mammary Gland Biol Neoplasia 7(1):93–105. doi: 10.1023/A:1015726608146 CrossRefPubMedGoogle Scholar
  28. 28.
    Calle EE, Heath CW Jr, Coates RJ, Liff JM, Franceschi S, Talamini R, Chantarakul N, Koetsawang S, Dd R, Ae M et al (1997) Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative group on hormonal factors in breast cancer. Lancet 350(9084):1047–1059. doi: 10.1016/S0140-6736(97)08233-0 CrossRefGoogle Scholar
  29. 29.
    Chlebowski RT, Anderson GL (2015) Menopausal hormone therapy and breast cancer mortality: clinical implications. Ther Adv Drug Saf 6(2):45–56. doi: 10.1177/2042098614568300 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Banks E (2015) An evidence-based future for menopausal hormone therapy. Women’s Health (Lond Engl) 11(6):785–788. doi: 10.2217/whe.15.37 CrossRefGoogle Scholar
  31. 31.
    Warren MP, Shu AR, Dominguez JE (2000) Menopause and Hormone Replacement, In: L J De Groot, P Beck-Peccoz, G Chrousos, K Dungan, A Grossman, JM Hershman, C Koch, R McLachlan, M New, R Rebar, F Singer, A Vinik, MO Weickert (Eds.) Endotext, South Dartmouth (MA)Google Scholar
  32. 32.
    Gupta PB, Proia D, Cingoz O, Weremowicz J, Naber SP, Weinberg RA, Kuperwasser C (2007) Systemic stromal effects of estrogen promote the growth of estrogen receptor-negative cancers. Cancer Res 67(5):2062–2071. doi: 10.1158/0008-5472.CAN-06-3895 CrossRefPubMedGoogle Scholar
  33. 33.
    McConnell JC, O’Connell OV, Brennan K, Weiping L, Howe M, Joseph L, Knight D, O’Cualain R, Lim Y, Leek A et al (2016) Increased peri-ductal collagen micro-organization may contribute to raised mammographic density. Breast Cancer Res 18(1):5. doi: 10.1186/s13058-015-0664-2 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Vigezzi L, Ramos JG, Kass L, Tschopp MV, Muñoz-de-Toro M, Luque EH, Bosquiazzo VL (2016) A deregulated expression of estrogen-target genes is associated with an altered response to estradiol in aged rats perinatally exposed to bisphenol a. Mol Cell Endocrinol 426:33–42. doi: 10.1016/j.mce.2016.02.010 CrossRefPubMedGoogle Scholar
  35. 35.
    Andreoli MF, Stoker C, Rossetti MF, Alzamendi A, Castrogiovanni D, Luque EH, Ramos JG (2015) Withdrawal of dietary phytoestrogens in adult male rats affects hypothalamic regulation of food intake, induces obesity and alters glucose metabolism. Mol Cell Endocrinol 401:111–119. doi: 10.1016/j.mce.2014.12.002 CrossRefPubMedGoogle Scholar
  36. 36.
    Altamirano GA, Muñoz-de-Toro M, Luque EH, Gomez AL, Delconte MB, Kass L (2015) Milk lipid composition is modified by perinatal exposure to bisphenol a. Mol Cell Endocrinol 411:258–267. doi: 10.1016/j.mce.2015.05.007 CrossRefPubMedGoogle Scholar
  37. 37.
    Kass L, Altamirano GA, Bosquiazzo VL, Luque EH, Muñoz-de-Toro M (2012) Perinatal exposure to xenoestrogens impairs mammary gland differentiation and modifies milk composition in Wistar rats. Reprod Toxicol 33(3):390–400. doi: 10.1016/j.reprotox.2012.02.002 CrossRefPubMedGoogle Scholar
  38. 38.
    Bosquiazzo VL, Vigezzi L, Muñoz-de-Toro M, Luque EH (2013) Perinatal exposure to diethylstilbestrol alters the functional differentiation of the adult rat uterus. J Steroid Biochem Mol Biol 138:1–9. doi: 10.1016/j.jsbmb.2013.02.011 CrossRefPubMedGoogle Scholar
  39. 39.
    Vigezzi L, Bosquiazzo VL, Kass L, Ramos JG, Muñoz-de-Toro M, Luque EH (2015) Developmental exposure to bisphenol a alters the differentiation and functional response of the adult rat uterus to estrogen treatment. Reprod Toxicol 52:83–92. doi: 10.1016/j.reprotox.2015.01.011 CrossRefPubMedGoogle Scholar
  40. 40.
    Kass L, Varayoud J, Ortega H, Muñoz-de-Toro M, Luque EH (2000) Detection of bromodeoxyuridine in formalin-fixed tissue. DNA denaturation following microwave or enzymatic digestion pretreatment is required. Eur J Histochem 44(2):185–191PubMedGoogle Scholar
  41. 41.
    Rudmann D, Cardiff R, Chouinard L, Goodman D, Kuttler K, Marxfeld H, Molinolo A, Treumann S, Yoshizawa K (2012) Proliferative and nonproliferative lesions of the rat and mouse mammary, Zymbal’s, preputial, and clitoral glands. Toxicol Pathol 40(6 Suppl):7S–39S. doi: 10.1177/0192623312454242 CrossRefPubMedGoogle Scholar
  42. 42.
    Kass L, Durando M, Altamirano GA, Manfroni-Ghibaudo GE, Luque EH, Muñoz-de-Toro M (2015) Prenatal bisphenol a exposure delays the development of the male rat mammary gland. Reprod Toxicol 54:37–46. doi: 10.1016/j.reprotox.2014.02.001 CrossRefPubMedGoogle Scholar
  43. 43.
    Lucas JN, Rudmann DG, Credille KM, Irizarry AR, Peter A, Snyder PW (2007) The rat mammary gland: morphologic changes as an indicator of systemic hormonal perturbations induced by xenobiotics. Toxicol Pathol 35(2):199–207. doi: 10.1080/01926230601156260 CrossRefPubMedGoogle Scholar
  44. 44.
    Rothschild TC, Boylan ES, Calhoon RE, Vonderhaar BK (1987) Transplacental effects of diethylstilbestrol on mammary development and tumorigenesis in female ACI rats. Cancer Res 47(16):4508–4516PubMedGoogle Scholar
  45. 45.
    Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, Rodabough RJ, Gilligan MA, Cyr MG, Thomson CA et al (2003) Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative randomized trial. JAMA 289(24):3243–3253. doi: 10.1001/jama.289.24.3243 CrossRefPubMedGoogle Scholar
  46. 46.
    Stefanick ML, Anderson GL, Margolis KL, Hendrix SL, Rodabough RJ, Paskett ED, Lane DS, Hubbell FA, Assaf AR, Sarto GE et al (2006) Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA 295(14):1647–1657. doi: 10.1001/jama.295.14.1647 CrossRefPubMedGoogle Scholar
  47. 47.
    Raafat AM, Hofseth LJ, Haslam SZ (2001) Proliferative effects of combination estrogen and progesterone replacement therapy on the normal postmenopausal mammary gland in a murine model. Am J Obstet Gynecol 184(3):340–349. doi: 10.1067/mob.2001.110447 CrossRefPubMedGoogle Scholar
  48. 48.
    Hofseth LJ, Raafat AM, Osuch JR, Pathak DR, Slomski CA, Haslam SZ (1999) Hormone replacement therapy with estrogen or estrogen plus medroxyprogesterone acetate is associated with increased epithelial proliferation in the normal postmenopausal breast. J Clin Endocrinol Metab 84(12):4559–4565. doi: 10.1210/jcem.84.12.6194 PubMedGoogle Scholar
  49. 49.
    Raafat AM, Li S, Bennett JM, Hofseth LJ, Haslam SZ (2001) Estrogen and estrogen plus progestin act directly on the mammary gland to increase proliferation in a postmenopausal mouse model. J Cell Physiol 187(1):81–89. doi: 10.1002/1097-4652(2001)9999:9999<::AID-JCP1056>3.0.CO;2-0 CrossRefPubMedGoogle Scholar
  50. 50.
    Mallepell S, Krust A, Chambon P, Brisken C (2006) Paracrine signaling through the epithelial estrogen receptor alpha is required for proliferation and morphogenesis in the mammary gland. Proc Natl Acad Sci U S A 103(7):2196–2201. doi: 10.1073/pnas.0510974103 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Brisken C, Park S, Vass T, Lydon JP, O’Malley BW, Weinberg RA (1998) A paracrine role for the epithelial progesterone receptor in mammary gland development. Proc Natl Acad Sci U S A 95(9):5076–5081CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Asselin-Labat ML, Vaillant F, Sheridan JM, Pal B, Wu D, Simpson ER, Yasuda H, Smyth GK, Martin TJ, Lindeman GJ et al (2010) Control of mammary stem cell function by steroid hormone signalling. Nature 465(7299):798–802. doi: 10.1038/nature09027 CrossRefPubMedGoogle Scholar
  53. 53.
    Joshi PA, Jackson HW, Beristain AG, Di Grappa MA, Mote PA, Clarke CL, Stingl J, Waterhouse PD, Khokha R (2010) Progesterone induces adult mammary stem cell expansion. Nature 465(7299):803–807. doi: 10.1038/nature09091 CrossRefPubMedGoogle Scholar
  54. 54.
    Haslam SZ (1988) Acquisition of estrogen-dependent progesterone receptors by normal mouse mammary gland. Ontogeny of mammary progesterone receptors. J Steroid Biochem 31(1):9–13. doi: 10.1016/0022-4731(88)90199-9 CrossRefPubMedGoogle Scholar
  55. 55.
    Ginsburg OM, Martin LJ, Boyd NF (2008) Mammographic density, lobular involution, and risk of breast cancer. Br J Cancer 99(9):1369–1374. doi: 10.1038/sj.bjc.6604635 CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Varayoud J, Monje L, Bernhardt T, Muñoz-de-Toro M, Luque EH, Ramos JG (2008) Endosulfan modulates estrogen-dependent genes like a non-uterotrophic dose of 17beta-estradiol. Reprod Toxicol 26(2):138–145. doi: 10.1016/j.reprotox.2008.08.004 CrossRefPubMedGoogle Scholar
  57. 57.
    Varayoud J, Ramos JG, Monje L, Bosquiazzo V, Muñoz-de-Toro M, Luque EH (2005) The estrogen receptor alpha sigma3 mRNA splicing variant is differentially regulated by estrogen and progesterone in the rat uterus. J Endocrinol 186(1):51–60. doi: 10.1677/joe.1.06099 CrossRefPubMedGoogle Scholar
  58. 58.
    Haslam SZ, Shyamala G (1979) Effect of oestradiol on progesterone receptors in normal mammary glands and its relationship with lactation. Biochem J 182(1):127–131. doi: 10.1042/bj1820127 CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    DeFranco DB (1999) Regulation of steroid receptor subcellular trafficking. Cell Biochem Biophys 30(1):1–24. doi: 10.1007/BF02737882 CrossRefPubMedGoogle Scholar
  60. 60.
    Giulivo M, Lopez de Alda M, Capri E, Barcelo D (2016) Human exposure to endocrine disrupting compounds: their role in reproductive systems, metabolic syndrome and breast cancer. A review. Environ Res 151:251–264. doi: 10.1016/j.envres.2016.07.011 CrossRefPubMedGoogle Scholar
  61. 61.
    Corrales J, Kristofco LA, Steele WB, Yates BS, Breed CS, Williams ES, Brooks BW (2015) Global assessment of bisphenol a in the environment: review and analysis of its occurrence and bioaccumulation. Dose Response 13(3):1559325815598308. doi: 10.1177/1559325815598308 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Durando M, Kass L, Perdomo V, Bosquiazzo VL, Luque EH, Muñoz-de-Toro M (2011) Prenatal exposure to bisphenol a promotes angiogenesis and alters steroid-mediated responses in the mammary glands of cycling rats. J Steroid Biochem Mol Biol 127(1–2):35–43. doi: 10.1016/j.jsbmb.2011.04.001 CrossRefPubMedGoogle Scholar
  63. 63.
    Betancourt AM, Eltoum IA, Desmond RA, Russo J, Lamartiniere CA (2010) In utero exposure to bisphenol a shifts the window of susceptibility for mammary carcinogenesis in the rat. Environ Health Perspect 118(11):1614–1619. doi: 10.1289/ehp.1002148 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Murray TJ, Maffini MV, Ucci AA, Sonnenschein C, Soto AM (2007) Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol a exposure. Reprod Toxicol 23(3):383–390. doi: 10.1016/j.reprotox.2006.10.002 CrossRefPubMedGoogle Scholar
  65. 65.
    Varayoud J, Ramos JG, Bosquiazzo VL, Muñoz-de-Toro M, Luque EH (2008) Developmental exposure to bisphenol a impairs the uterine response to ovarian steroids in the adult. Endocrinology 149(11):5848–5860. doi: 10.1210/en.2008-0651 CrossRefPubMedGoogle Scholar
  66. 66.
    Doherty LF, Bromer JG, Zhou Y, Aldad TS, Taylor HS (2010) In utero exposure to diethylstilbestrol (DES) or bisphenol-a (BPA) increases EZH2 expression in the mammary gland: an epigenetic mechanism linking endocrine disruptors to breast cancer. Horm Cancer 1(3):146–155. doi: 10.1007/s12672-010-0015-9 CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Bhan A, Hussain I, Ansari KI, Bobzean SA, Perrotti LI, Mandal SS (2014) Histone methyltransferase EZH2 is transcriptionally induced by estradiol as well as estrogenic endocrine disruptors bisphenol-a and diethylstilbestrol. J Mol Biol 426(20):3426–3441. doi: 10.1016/j.jmb.2014.07.025 CrossRefPubMedGoogle Scholar
  68. 68.
    Altamirano GA, Ramos JG, Gomez AL, Luque EH, Muñoz-de-Toro M, Kass L (2017) Perinatal exposure to bisphenol a modifies the transcriptional regulation of the beta-casein gene during secretory activation of the rat mammary gland. Mol Cell Endocrinol 439:407-418. doi: 10.1016/j.mce.2016.09.032
  69. 69.
    Bhan A, Hussain I, Ansari KI, Bobzean SA, Perrotti LI, Mandal SS (2014) Bisphenol-a and diethylstilbestrol exposure induces the expression of breast cancer associated long noncoding RNA HOTAIR in vitro and in vivo. J Steroid Biochem Mol Biol 141:160–170. doi: 10.1016/j.jsbmb.2014.02.002 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Dhimolea E, Wadia PR, Murray TJ, Settles ML, Treitman JD, Sonnenschein C, Shioda T, Soto AM (2014) Prenatal exposure to BPA alters the epigenome of the rat mammary gland and increases the propensity to neoplastic development. PLoS One 9(7):e99800. doi: 10.1371/journal.pone.0099800 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Ayelen L. Gomez
    • 1
  • Melisa B. Delconte
    • 1
  • Gabriela A. Altamirano
    • 1
  • Lucia Vigezzi
    • 1
  • Veronica L. Bosquiazzo
    • 1
  • Luís F. Barbisan
    • 2
  • Jorge G. Ramos
    • 1
  • Enrique H. Luque
    • 1
  • Mónica Muñoz-de-Toro
    • 1
  • Laura Kass
    • 1
    Email author
  1. 1.Instituto de Salud y Ambiente del Litoral (ISAL)Universidad Nacional del Litoral (UNL)–Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Bioquímica y Ciencias Biológicas, UNLSanta FeArgentina
  2. 2.Departamento de Morfologia, Instituto de BiociênciasUniversidade Estadual Paulista (UNESP)BotucatuBrazil

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