Methoxychlor metabolite HPTE alters viability and differentiation of embryonic thymocytes from C57BL/6 mice

References

• Ahmed S. 2000. The immune system as a potential target for environmental estrogens (endocrine disrupters): A new emerging field. Toxicology. 150:191–206.
   PubMed Web of Science ®Google Scholar
• Ahmed S, Hissong B, Verthelyi D, Donner K, Becker K, Karpuzoglu-Sahin E. 1999. Gender and risk of autoimmune diseases: Possible role of estrogenic compounds. Environ. Health Perspect. 107(S5):681–686.
   Web of Science ®Google Scholar
• Altman N, Krzywinski M. 2017. Points of significance: p-Values and the search for significance. Nat Methods. 14:3–4.
   Web of Science ®Google Scholar
• Azzam H, DeJarnette J, Huang K, Emmons R, Park C, Sommers C, Love P. 2001. Fine tuning of TCR signaling by CD5. J Immunol. 166:5464–5472.
   PubMed Web of Science ®Google Scholar
• Azzam H, Grinberg A, Lui K, Shen H, Shores E, Love P. 1998. CD5 expression is developmentally regulated by T-cell receptor (TCR) signals and TCR avidity. J Exp Med. 188:2301–2311.
   PubMed Web of Science ®Google Scholar
• Baldwin T, Sandau M, Jameson S, Hogquist K. 2005. The timing of TCR alpha expression critically influences T-cell development and selection. J Exp Med. 202:111–121.
   PubMed Web of Science ®Google Scholar
• Barnes D, Page D, Duke S, White K. 1983. Subchronic toxicology of diethystilbestrol in the mouse. Drug Chem Toxicol. 6:455–485.
   PubMed Web of Science ®Google Scholar
• Berthois Y, Katzenellenbogen J, Katzenellenbogen B. 1986. Phenol red in tissue culture media is a weak estrogen: Implications concerning the study of estrogen-responsive cells in culture. Proc Natl Acad Sci USA 83:2496–2500.
   PubMed Web of Science ®Google Scholar
• Besteman E, Zimmerman K, Holladay S. 2005. Diethylstilbestrol (DES)-induced fetal thymic atrophy in C57BL/6 mice: Inhibited thymocyte differentiation and increased apoptotic cell death. Int J Toxicol. 24:231–239.
   PubMed Web of Science ®Google Scholar
• Bland J, Altman D. 1995. Multiple significance tests: The Bonferroni method. BMJ 310:170.
   PubMed Web of Science ®Google Scholar
• Botella B, Crespo J, Rivas A, Cerrillo I, Olea-Serrano M, Olea N. 2004. Exposure of women to organochlorine pesticides in Southern Spain. Environ Res. 96:34–40.
   PubMed Web of Science ®Google Scholar
• Brown N, Nagarkatti M, Nagarkatti P. 2006a. Diethylstilbestrol alters positive and negative selection of T-cells in the thymus and modulates T-cell repertoire in periphery. Toxicol Appl Pharmacol. 212:119–126.
   PubMed Web of Science ®Google Scholar
• Brown N, Nagarkatti M, Nagarkatti P. 2006b. Induction of apoptosis in murine fetal thymocytes following perinatal exposure to diethylstilbestrol. Int J Toxicol. 25:9–15.
   PubMed Web of Science ®Google Scholar
• Brown N. 2005. Chapter V. Diethylstilbestrol-induced apoptosis requires T-cell-stromal cells interactions. In: The mechanism of T-cell Dysfunction Induced by Diethylstilbestrol [Doctoral dissertation]. Virginia Commonwealth University.
   Google Scholar
• Bulger W, Muccitelli R, Kupfer D. 1978. Studies on the in vivo and in vitro estrogenic activities of methoxychlor and its metabolites. Role of hepatic mono-oxygenase in methoxychlor activation. Biochem Pharmacol. 27:2417–2423.
   PubMed Web of Science ®Google Scholar
• CA EPA (California Environmental Protection Agency). 2010. Public Health Goal for Methoxychlor in Drinking Water. Pesticide and Environmental Toxicology Branch Office of Environmental Health Hazard Assessment.
   Google Scholar
• Calemine J, Gogal R, Lengi A, Sponenberg P, Ahmed S. 2002. Immunomodulation by diethyl-stilbestrol is dose and gender related: Effects on thymocyte apoptosis and mitogen-induced proliferation. Toxicology. 178:101–118.
   PubMed Web of Science ®Google Scholar
• Carson R. 2002. Silent Spring. 40th anniversary edition. New York: Mariner Books.
   Google Scholar
• Caserta D, Mantovani A, Marci R, Fazi A, Ciardo F, La Rocca C, Moscarini M. 2011. Environment and women's reproductive health. Human Reprod Update. 17:418–433.
   PubMed Web of Science ®Google Scholar
• Chapin R, Harris M, Davis B, Ward S, Wilson R, Mauney M, Lockhart A, Smialowicz R, Moser V, Burka L, et al. 1997. The effects of perinatal/juvenile methoxychlor exposure on adult rat nervous, immune, and reproductive system function. Fundam Appl Toxicol. 40:138–157.
   PubMedGoogle Scholar
• Cibotti R, Punt J, Dash K, Sharrow S, Singer A. 1997. Surface molecules that drive T-cell development in vitro in the absence of thymic epithelium and in the absence of lineage-specific signals. Immunity 6:245–255.
   PubMed Web of Science ®Google Scholar
• Damgaard I, Skakkebaek N, Toppari J, Virtanen H, Shen H, Schramm K. and the Nordic Cryptorchidism Study Group. 2006. Persistent pesticides in human breastmilk and crypt-orchidism. Environ Health Perspect. 114:1133.
   PubMed Web of Science ®Google Scholar
• Dietert R. 2014. Developmental immunotoxicity, perinatal programming, and non-communicable diseases: Focus on human studies. Adv Med. 2014:18.
   Google Scholar
• Do Y, Ryu S, Nagarkatti M, Nagarkatti P. 2002. Role of death receptor pathway in estradiol-induced T-cell apoptosis in vivo. Toxicol Sci. 70:63–72.
   PubMed Web of Science ®Google Scholar
• Erlandsson M, Ohlsson C, Gustafsson J, Carlsten H. 2001. Role of oestrogen receptors α and β in immune organ development and in estrogen-mediated effects on thymus. Immunology. 103:17–25.
   PubMed Web of Science ®Google Scholar
• Fenaux J, Gogal R, Ahmed S. 2004. Diethylstilbestrol exposure during fetal development affects thymus: Studies in fourteen-month-old mice. J Reprod Immunol. 64:75–90.
   PubMed Web of Science ®Google Scholar
• Fleck M, Zhou T, Tatsuta T, Yang P, Wang Z, Mountz J. 1998. Fas/Fas ligand signaling during gestational T-cell development. J Immunol. 160:3766–3775.
   PubMed Web of Science ®Google Scholar
• Folmar L, Hemmer M, Denslow N, Kroll K, Chen J, Cheek A, Richman H, Meredith H, Grau E. 2002. A comparison of the estrogenic potencies of estradiol, ethynylestradiol, diethylstilbestrol, nonylphenol and methoxychlor in vivo and in vitro. Aquat Toxicol. 60:101–110.
   PubMed Web of Science ®Google Scholar
• Frawley R, White K, Brown R, Musgrove D, Walker N, Germolec D. 2011. Gene expression alterations in immune system pathways in the thymus after exposure to immunosuppressive chemicals. Environm Health Perspect. 119:371.
   PubMed Web of Science ®Google Scholar
• Fukuyama T, Kosaka T, Tajima Y, Hayashi K, Shutoh Y, Harada T. 2011. Detection of thymocytes apoptosis in mice induced by organochlorine pesticides methoxychlor. Immunopharmacol Immunotoxicol. 33:193–200.
   PubMed Web of Science ®Google Scholar
• Fukuyama T, Tajima Y, Ueda H, Hayashi K, Shutoh Y, Harada T, Kosaka T. 2010. Apoptosis in immunocytes induced by several types of pesticides. J Immunotoxicol. 7:39–56.
   PubMed Web of Science ®Google Scholar
• Gaido K, Leonard L, Maness S, Hall J, McDonnell D, Saville B, Safe S. 1999. Differential inter-action of methoxychlor metabolite 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane with estrogen receptors α and β. Endocrinology. 140:5746–5753.
   PubMed Web of Science ®Google Scholar
• Gaido K, Maness S, McDonnell D, Dehal S, Kupfer D, Safe S. 2000. Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: Structure-activity studies. Mol Pharmacol. 58:852–858.
   PubMed Web of Science ®Google Scholar
• Gu M, Min J, Kim E. 2002. Toxicity monitoring and classification of endocrine-disrupting chemicals (EDC) using recombinant bioluminescent bacteria. Chemosphere. 46:289–294.
   PubMed Web of Science ®Google Scholar
• Gunderson E. 1988. FDA Total Diet Study, April 1982-April 1984, dietary intakes of pesticides, selected elements, and other chemicals. J Assoc. 71:1200–1209.
   Google Scholar
• Guo T, Chi R, Zhang X, Musgrove D, Weis C, Germolec D, White K. 2006. Modulation of immune response following dietary genistein exposure in F0 and F1 generations of C57BL/6 mice: Evidence of thymic regulation. Food Chem Toxicol. 44:316–325.
   PubMed Web of Science ®Google Scholar
• Guo T, White K, Brown R, Delclos K, Newbold R, Weis C, Germolec D, McCay J. 2002. Genistein modulates splenic natural killer cell activity, antibody-forming cell response, and phenotypic marker expression in F0 and F1 generations of Sprague–Dawley rats. Toxicol Appl Pharmacol. 181:219–227.
   PubMed Web of Science ®Google Scholar
• Harris R, Waring R. 2012. Diethylstilboestrol-a long-term legacy. Maturitas. 72:108–112.
   PubMed Web of Science ®Google Scholar
• Heilmann C, Grandjean P, Weihe P, Nielsen F, Budtz-Jørgensen E. 2006. Reduced antibody responses to vaccinations in children exposed to polychlorinated biphenyls. PLoS Med. 3:e311.
   PubMed Web of Science ®Google Scholar
• Heindel J, Balbus J, Birnbaum L, Brune-Drisse M, Grandjean P, Gray K, Landrigan P, Sly P, Suk W, Slechta D, et al. 2016. Developmental origins of health and disease: Integrating environmental influences. Endocrinology. 156:3416–3421.
   Web of Science ®Google Scholar
• Hewitt S, Korach K. 2011. Estrogenic activity of bisphenol A and 2,2-bis-(p-hydroxy-phenyl)-1,1,1-trichloroethane (HPTE) demonstrated in mouse uterine gene profiles. Environ Health Perspect. 119:63.
   PubMed Web of Science ®Google Scholar
• Hodges L, Bergerson J, Hunter D, Walker C. 2000. Estrogenic effects of organochlorine pesticides on uterine leiomyoma cells in vitro. Toxicol Sci. 54:355–364.
   PubMed Web of Science ®Google Scholar
• Hogquist K, Xing Y, Hsu F, Shapiro V. 2015. T-Cell adolescence: Maturation events beyond positive selection. J Immunol. 195:1351–1357.
   PubMed Web of Science ®Google Scholar
• Holladay S, Blaylock B, Comment C, Heindel J, Fox W, Korach K, Luster M. 1993. Selective prothymocyte targeting by prenatal diethylstilbesterol exposure. Cell Immunol. 152:131–142.
   PubMed Web of Science ®Google Scholar
• Jiang D, Zheng L, Lenardo M. 1999. Caspases in T-cell receptor-induced thymocyte apoptosis. Cell Death Diff. 6:402–411.
   PubMed Web of Science ®Google Scholar
• Kaplan B, Li J, LaPres J, Pruett S, Karmaus P. 2015. Contributions of non-hematopoietic cells and mediators to immune responses: Implications for immunotoxicology. Toxicol Sci. 145:214–232.
   PubMed Web of Science ®Google Scholar
• Kapoor I, Metcalf R, Nystrom R, Sangha G. 1970. Comparative metabolism of methoxychlor, methiochlor, and DDT in mouse, insects, and in a model ecosystem. J Agric Food Chem. 18:1145–1152.
   PubMed Web of Science ®Google Scholar
• Kishimoto H, Sprent J. 1997. Negative selection in the thymus includes semimature T cells. J Exp Med. 185:263–272.
   PubMed Web of Science ®Google Scholar
• Kishimoto H, Sprent J. 2001. A defect in central tolerance in NOD mice. Nat Immunol. 2:1025.
   PubMed Web of Science ®Google Scholar
• Klinge C. 2015. miRNAs regulated by estrogens, tamoxifen, and endocrine disruptors and their downstream gene targets. Mol Cell Endocrinol. 418:273–297.
   PubMed Web of Science ®Google Scholar
• Kurd N, Robey E. 2016. T-Cell selection in the thymus: A spatial and temporal perspective. Immunol Rev. 271:114–126.
   PubMed Web of Science ®Google Scholar
• Lai Z, Fiore N, Gasiewicz T, Silverstone A. 1998. 2,3,7,8-Tetrachlorodibenzo-p-dioxin and diethylstilbestrol affect thymocytes at different stages of development in fetal thymus organ culture. Toxicol Appl Pharmacol. 149:167–177.
   PubMed Web of Science ®Google Scholar
• Lai Z, Fiore N, Hahn P, Gasiewicz T, Silverstone A. 2000. Differential effects of diethylstilbestrol and 2,3,7,8-tetrachlorodibenzo-p-dioxin on thymocyte differentiation, proliferation, and apoptosis in bcl-2 transgenic mouse fetal thymus organ culture. Toxicol Appl Pharmacol. 168:15–24.
   PubMed Web of Science ®Google Scholar
• Levin E, Hammes S. 2016. Nuclear receptors outside the nucleus: Extranuclear signalling by steroid receptors. Nat Rev Mol Cell Biol. 17:783–797.
   PubMed Web of Science ®Google Scholar
• Li H, Dehal S, Kupfer D. 1995. Induction of the hepatic CYP2B and CYP3A enzymes by the proestrogenic pesticide methoxychlor and by DDT in the rat. Effects on methoxychlor metabolism. J Biochem Toxicol. 10:51–61.
   PubMedGoogle Scholar
• Luster M, Faith R, McLachlan J, Clark G. 1979. Effect of in utero exposure to diethylstilbestrol on the immune response in mice. Toxicol Appl Pharmacol. 47:279–285.
   PubMed Web of Science ®Google Scholar
• Luster M, Hayes H, Korach K, Tucker A, Dean J, Greenlee W, Boorman G. 1984. Estrogen immunosuppression is regulated through estrogenic responses in the thymus. J Immunol. 133:110–116.
   PubMed Web of Science ®Google Scholar
• Luz N, Marques M, Ayub A, Correa P. 1969. Effects of estradiol upon the thymus and lymphoid organs of immature female rats. Am J Obstet Gynecol. 105:525–528.
   PubMed Web of Science ®Google Scholar
• Manikkam M, Haque M, Guerrero-Bosagna C, Nilsson E, Skinner M. 2014. Pesticide methoxychlor promotes the epigenetic transgenerational inheritance of adult-onset disease through the female germline. PloS One 9:e102091.
   PubMed Web of Science ®Google Scholar
• Meeker J. 2010. Exposure to environmental endocrine disrupting compounds and men’s health. Maturitas. 66:236–241.
   PubMed Web of Science ®Google Scholar
• Melichar H, Ross J, Taylor K, Robey E. 2015. Stable interactions and sustained TCR signaling characterize thymocyte–thymocyte interactions that support negative selection. J Immunol. 194:1057–1061.
   PubMed Web of Science ®Google Scholar
• Melnick S, Cole P, Anderson D, Herbst A. 1987. Rates and risks of diethylstilbestrol-related clear-cell adenocarcinoma of the vagina and cervix. New Engl J Med. 316:514–516.
   PubMed Web of Science ®Google Scholar
• Mor G, Muñoz A, Redlinger R, Silva I, Song J, Lim C, Kohen F. 2001. The role of the Fas/Fas ligand system in estrogen-induced thymic alteration. Am J Reprod Immunol. 46:298–307.
   PubMed Web of Science ®Google Scholar
• National Research Council. 2011. Guide for the care and use of laboratory animals. 8th ed. Washington (DC): National Academies Press.
   Google Scholar
• Noller K, Blair P, O’Brien P, Melton L, Offord J, Kaufman R, Colton T. 1988. Increased occurrence of autoimmune disease among women exposed in utero to diethylstilbestrol. Fertil Steril. 49:1080–1082.
   PubMed Web of Science ®Google Scholar
• Okasha S, Ryu S, Do Y, McKallip R, Nagarkatti M, Nagarkatti P. 2001. Evidence for estradiol-induced apoptosis and dysregulated T-cell maturation in the thymus. Toxicology. 163:49–62.
   PubMed Web of Science ®Google Scholar
• Ousterhout J, Struck R, Nelson J. 1981. Estrogenic activities of methoxychlor metabolites. Biochem Pharmacol. 30:2869–2871.
   PubMed Web of Science ®Google Scholar
• Pozzesi N, Fierabracci A, Liberati A, Martelli M, Ayroldi E, Riccardi C, Delfino D. 2014. Role of caspase-8 in thymus function. Cell Death Diff. 21:226–233.
   PubMed Web of Science ®Google Scholar
• Punt J, Osborne B, Takahama Y, Sharrow S, Singer A. 1994. Negative selection of CD4+CD8+ thymocytes by T-cell receptor-induced apoptosis requires a costimulatory signal that can be provided by CD28. J Exp Med. 179:709–713.
   PubMed Web of Science ®Google Scholar
• R Core Team. 2013. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing.
   Google Scholar
• Rawn D, Cao X, Doucet J, Davies D, Sun W, Dabeka R, Newsome W. 2004. Canadian Total Diet Study in 1998: Pesticide levels in foods from Whitehorse, Yukon, Canada, and corresponding dietary intake estimates. Food Additives Contam. 21:232–250.
   PubMed Web of Science ®Google Scholar
• Reed C, Fenton S. 2013. Exposure to diethylstilbestrol during sensitive life stages: A legacy of heritable health effects. Birth Defects Res C Embryo Today. 99:134–146.
   PubMed Web of Science ®Google Scholar
• Rijhsinghani A, Bhatia S, Tygrett L, Waldschmidt T. 1996. Effect of pregnancy on thymic T-cell development. Am J Reprod Immunol. 35:523–528.
   PubMed Web of Science ®Google Scholar
• Schettgen T, Alt A, Esser A, Kraus T. 2015. Current data on background burden to the persistent organochlorine pollutants HCB, p,p′-DDE as well as PCB 138, PCB 153 and PCB 180 in plasma of the general population in Germany. Int J Hyg Environ Health. 218:380–385.
   PubMed Web of Science ®Google Scholar
• Serwold T, Hochedlinger K, Inlay M, Jaenisch R, Weissman I. 2007. Early TCR expression and aberrant T-cell development in mice with endogenous prerearranged T-cell receptor genes. J Immunol. 179:928–938.
   PubMed Web of Science ®Google Scholar
• Shelby M, Newbold R, Tully D, Chae K, Davis V. 1996. Assessing environmental chemicals for estrogenicity using a combination of in vitro and in vivo assays. Environ Health Perspect. 104:1296–1300.
   PubMed Web of Science ®Google Scholar
• Shen H, Main K, Virtanen H, Damggard I, Haavisto A, Kaleva M, Toppari J. 2007. From mother to child: Investigation of prenatal and postnatal exposure to persistent bioaccumulating toxicants using breastmilk and placenta biomonitoring. Chemosphere. 67:S256–S262.
   PubMed Web of Science ®Google Scholar
• Shortman K, Vremec D, Egerton M. 1991. The kinetics of T-cell antigen receptor expression by subgroups of CD4 + CD8+ thymocytes: Delineation of CD4 + 8+3(2+) thymocytes as post-selection intermediates leading to mature T-cells. J Exp Med. 173:323–332.
   PubMed Web of Science ®Google Scholar
• Silverstone A, Frazier D, Fiore N, Soults J, Gasiewicz T. 1994. Dexamethasone, β-estradiol, and 2,3,7,8-tetrachlorodibenzo-p-dioxin elicit thymic atrophy through different cellular targets. Toxicol Appl Pharmacol. 126:248–259.
   PubMed Web of Science ®Google Scholar
• Singer A, Adoro S, Park J. 2008. Lineage fate and intense debate: Myths, models and mechanisms of CD4- versus CD8-lineage choice. Nat Rev Immunol. 8:788–801.
   PubMed Web of Science ®Google Scholar
• Singh N, Singh U, Nagarkatti P, Nagarkatti M. 2012. Prenatal exposure of mice to diethylstilbestrol disrupts T-cell differentiation by regulating Fas/Fas ligand expression through estrogen receptor element and NF-κB motifs. J Pharmacol Exp Ther. 343:351–361.
   PubMed Web of Science ®Google Scholar
• Skånland S, Moltu K, Berge T, Aandahl E, Taskén K. 2014. T-Cell co-stimulation through the CD2 and CD28 co-receptors induces distinct signalling responses. Biochem J. 460:399–410.
   PubMed Web of Science ®Google Scholar
• Staples J, Fiore N, Frazier D, Gasiewicz T, Silverstone A. 1998. Overexpression of the anti-apoptotic oncogene, bcl-2, in the thymus does not prevent thymic atrophy induced by estradiol or 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Appl Pharmacol. 151:200–210.
   PubMed Web of Science ®Google Scholar
• Staples J, Gasiewicz T, Fiore N, Lubahn D, Korach K, Silverstone A. 1999. Estrogen receptor alpha is necessary in thymic development and estradiol-induced thymic alterations. J Immunol. 163:4168–4174.
   PubMed Web of Science ®Google Scholar
• Starr T, Jameson S, Hogquist K. 2003. Positive and negative selection of T cells. Annu Rev Immunol. 21:139–176.
   PubMed Web of Science ®Google Scholar
• Stuchal L, Kleinow K, Stegeman J, James M. 2006. Demethylation of the pesticide methoxy-chlor in liver and intestine from untreated, methoxychlor-treated, and 3-methylcholanthrene-treated channel catfish (Ictalurus punctatus): Evidence for roles of CYP1 and CYP3A family isozymes. Drug Metab Disposit. 34:932–938.
   PubMed Web of Science ®Google Scholar
• Takeuchi Y, Kosaka T, Hayashi K, Ishimine S, Ohtsuka R, Kuwahara M, Yoshida T, Takahashi N, Chiba Y, Takeda M, et al. 2004. Alterations in the developing immune system of the rat after perinatal exposure to methoxychlor. J Toxicol Pathol. 17:165–170.
   Google Scholar
• Takeuchi Y, Kosaka T, Hayashi K, Takeda M, Yoshida T, Fujisawa H, Teramoto S, Maita K, Harada T. 2002. Thymic atrophy induced by methoxychlor in rat pups. Toxicol Lett. 135:199–207.
   PubMed Web of Science ®Google Scholar
• Tarakhovsky A, Kanner S, Hombach J, Ledbetter J, Muller W, Killeen N, Rajewsky K. 1995. A role for CD5 in TCR-mediated signal transduction and thymocyte selection. Science. 269:535.
   PubMed Web of Science ®Google Scholar
• Wang C, Dehghani B, Magrisso I, Rick E, Bonhomme E, Cody D, Elenich L, Subramanian S, Murphy S, Kelly M, et al. 2008. GPR30 contributes to estrogen-induced thymic atrophy. Mol Endocrinol. 22:636–648.
   PubMed Web of Science ®Google Scholar
• Watson C, Bulayeva N, Wozniak A, Alyea R. 2007. Xenoestrogens are potent activators of nongenomic estrogenic responses. Steroids 72:124–134.
   PubMed Web of Science ®Google Scholar
• White K, Germolec D, Booker C, Hernendez D, McCay J, Delclos K, Newbold R, Weis C, Guo T. 2005. Dietary methoxychlor exposure modulates splenic natural killer cell activity, antibody-forming cell response and phenotypic marker expression in F0 and F1 generations of Sprague Dawley rats. Toxicology. 207:271–281.
   PubMed Web of Science ®Google Scholar
• Winans B, Humble M, Lawrence P. 2011. Environmental toxicants and the developing immune system: A missing link in the global battle against infectious disease? Reprod Toxicol. 31:327–336.
   PubMed Web of Science ®Google Scholar
• Xu Z, Liu J, Gu L, Huang B, Pan X. 2017. Biological effects of xenoestrogens and the functional mechanisms via genomic and non-genomic pathways. Environ Rev. 25:306–322.
   Google Scholar
• Yellayi S, Naaz A, Szewczykowski M, Sato T, Woods J, Chang J, Segre M, Allred C, Helferich W, Cooke P. 2002. The phytoestrogen genistein induces thymic and immune changes: A human health concern? Proc Natl Acad Sci USA 99:7616–7621.
   PubMed Web of Science ®Google Scholar
• Zoller A, Kersh G. 2006. Estrogen induces thymic atrophy by eliminating early thymic progenitors and inhibiting proliferation of beta-selected thymocytes. J Immunol. 176:7371–7378.
   PubMed Web of Science ®Google Scholar
• Zoller A, Schnell F, Kersh G. 2007. Murine pregnancy leads to reduced proliferation of maternal thymocytes and decreased thymic emigration. Immunology. 121:207–215.
   PubMed Web of Science ®Google Scholar