Download PDF
Semin Reprod Med 2010; 28(1): 059-068
DOI: 10.1055/s-0029-1242995
© Thieme Medical Publishers

Dioxin and Endometrial Progesterone Resistance

Kaylon L. Bruner-Tran1 , Tianbing Ding1 , Kevin G. Osteen1
  • 1Department of Obstetrics and Gynecology, Women's Reproductive Health Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee
Further Information

Publication History

Publication Date:
26 January 2010 (online)

    Permissions and Reprints

ABSTRACT

Development of endometriosis likely requires multiple, interactive mechanisms involving both the endocrine and immune systems. Environmental toxicants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are of particular interest as potential contributory agents in the development of this disease because they can disrupt both systems. Nevertheless, defining the potential role that environmental exposure to TCDD plays in the development of endometriosis requires a better understanding of how this toxicant affects the biological processes that promote the disease. Although the disease mechanism(s) responsible for progesterone resistance in the endometrium of endometriosis patients remains speculative, our studies indicate that developmental exposure of mice to TCDD leads to a progesterone-resistant phenotype in adult animals that can persist for several generations. These studies and others underscore the importance of developing a greater understanding of the mechanisms of TCDD action that relate to reproductive disorders such as endometriosis.

KEYWORDS

Endometriosis - TCDD - developmental exposure

REFERENCES

  • 1 Sampson J A. Peritoneal endometriosis due to menstrual dissemination of endometrial tissues into the peritoneal cavity.  Am J Obstet Gynecol. 1927;  14 422-469
    CrossrefPubMedGoogle Scholar
  • 2 Giudice L C, Kao L C. Endometriosis.  Lancet. 2004;  364(9447) 1789-1799
    CrossrefPubMedGoogle Scholar
  • 3 Bulun S E. Endometriosis.  N Engl J Med. 2009;  360(3) 268-279
    CrossrefPubMedGoogle Scholar
  • 4 Bruner-Tran K L, Yeaman G R, Crispens M A, Igarashi T M, Osteen K G. Dioxin may promote inflammation-related development of endometriosis.  Fertil Steril. 2008;  89(5, Suppl) 1287-1298
    CrossrefPubMedGoogle Scholar
  • 5 Foster W G. Environmental estrogens and endocrine disruption: importance of comparative endocrinology.  Endocrinology. 2008;  149(9) 4267-4268
    CrossrefPubMedGoogle Scholar
  • 6 Crain D A, Janssen S J, Edwards T M et al.. Female reproductive disorders: the roles of endocrine-disrupting compounds and developmental timing.  Fertil Steril. 2008;  90(4) 911-940
    CrossrefPubMedGoogle Scholar
  • 7 Okino S T, Whitlock Jr J P. The aromatic hydrocarbon receptor, transcription, and endocrine aspects of dioxin action.  Vitam Horm. 2000;  59 241-264
    PubMedGoogle Scholar
  • 8 Kerkvliet N I. AHR-mediated immunomodulation: the role of altered gene transcription.  Biochem Pharmacol. 2009;  77(4) 746-760
    CrossrefPubMedGoogle Scholar
  • 9 Heindel J J. Role of exposure to environmental chemicals in the developmental basis of reproductive disease and dysfunction.  Semin Reprod Med. 2006;  24(3) 168-177
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 National Toxicology Program .Current directions and emerging strategies, 2001. Available at: http://ntp.niehs.nih.gov/ntp/Main_Pages/PUBS/NTP2001CurrDir.pdf Accessed April 2009
    Google Scholar
  • 11 Birnbaum L S. Endocrine effects of prenatal exposure to PCBs, dioxins, and other xenobiotics: implications for policy and future research.  Environ Health Perspect. 1994;  102(8) 676-679
    CrossrefPubMedGoogle Scholar
  • 12 Harrad S, Wang Y, Sandaradura S, Leeds A. Human dietary intake and excretion of dioxin-like compounds.  J Environ Monit. 2003;  5(2) 224-228
    CrossrefPubMedGoogle Scholar
  • 13 Pompa G, Caloni F, Fracchiolla M L. Dioxin and PCB contamination of fish and shellfish: assessment of human exposure. Review of the international situation.  Vet Res Commun. 2003;  27(Suppl 1) 159-167
    PubMedGoogle Scholar
  • 14 Schecter A, Wallace D, Pavuk M, Piskac A, Päpke O. Dioxins in commercial United States baby food.  J Toxicol Environ Health A. 2002;  65(23) 1937-1943
    CrossrefPubMedGoogle Scholar
  • 15 Domingo J L, Bocio A. Levels of PCDD/PCDFs and PCBs in edible marine species and human intake: a literature review.  Environ Int. 2007;  33(3) 397-405
    CrossrefPubMedGoogle Scholar
  • 16 Dewailly E, Ryan J J, Laliberté C et al.. Exposure of remote maritime populations to coplanar PCBs.  Environ Health Perspect. 1994;  102(Suppl 1) 205-209
    PubMedGoogle Scholar
  • 17 Focant J F, Pirard C, Thielen C, De Pauw E. Levels and profiles of PCDDs, PCDFs and cPCBs in Belgian breast milk. Estimation of infant intake.  Chemosphere. 2002;  48(8) 763-770
    CrossrefPubMedGoogle Scholar
  • 18 Koninckx P R, Braet P, Kennedy S H, Barlow D H. Dioxin pollution and endometriosis in Belgium.  Hum Reprod. 1994;  9(6) 1001-1002
    PubMedGoogle Scholar
  • 19 De Felip E, Porpora M G, di Domenico A et al.. Dioxin-like compounds and endometriosis: a study on Italian and Belgian women of reproductive age.  Toxicol Lett. 2004;  150(2) 203-209
    CrossrefPubMedGoogle Scholar
  • 20 Bruner-Tran K L, Eisenberg E, Yeaman G R, Anderson T A, McBean J, Osteen K G. Steroid and cytokine regulation of matrix metalloproteinase expression in endometriosis and the establishment of experimental endometriosis in nude mice.  J Clin Endocrinol Metab. 2002;  87(10) 4782-4791
    CrossrefPubMedGoogle Scholar
  • 21 Kao L C, Germeyer A, Tulac S et al.. Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility.  Endocrinology. 2003;  144(7) 2870-2881
    CrossrefPubMedGoogle Scholar
  • 22 Bruner-Tran K L, Rier S E, Eisenberg E, Osteen K G. The potential role of environmental toxins in the pathophysiology of endometriosis.  Gynecol Obstet Invest. 1999;  48(Suppl 1) 45-56
    CrossrefPubMedGoogle Scholar
  • 23 Psychoyos A. Uterine receptivity for nidation.  Ann N Y Acad Sci. 1986;  476 36-42
    CrossrefPubMedGoogle Scholar
  • 24 Bergh P A, Navot D. The impact of embryonic development and endometrial maturity on the timing of implantation.  Fertil Steril. 1992;  58(3) 537-542
    PubMedGoogle Scholar
  • 25 Edwards R G. Physiological and molecular aspects of human implantation.  Hum Reprod. 1995;  10(Suppl 2) 1-13
    CrossrefPubMedGoogle Scholar
  • 26 Tabibzadeh S. Human endometrium: an active site of cytokine production and action.  Endocr Rev. 1991;  12(3) 272-290
    CrossrefPubMedGoogle Scholar
  • 27 Giudice L C. Growth factors and growth modulators in human uterine endometrium: their potential relevance to reproductive medicine.  Fertil Steril. 1994;  61(1) 1-17
    PubMedGoogle Scholar
  • 28 Simón C, Frances A, Piquette G, Hendrickson M, Milki A, Polan M L. Interleukin-1 system in the materno-trophoblast unit in human implantation: immunohistochemical evidence for autocrine/paracrine function.  J Clin Endocrinol Metab. 1994;  78(4) 847-854
    CrossrefPubMedGoogle Scholar
  • 29 Tazuke S I, Giudice L C. Growth factors and cytokines in endometrium, embryonic development, and maternal: embryonic interactions.  Semin Reprod Endocrinol. 1996;  14(3) 231-245
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Critchley H O, Kelly R W, Brenner R M, Baird D T. The endocrinology of menstruation—a role for the immune system.  Clin Endocrinol (Oxf). 2001;  55(6) 701-710
    CrossrefPubMedGoogle Scholar
  • 31 Lessey B A, Killam A P, Metzger D A, Haney A F, Greene G L, McCarty K D. Immunohistochemical analysis of human uterine estrogen and progesterone receptors in the normal human uterus throughout the menstrual cycle.  J Clin Endocrinol Metab. 1988;  67 334-340
    CrossrefPubMedGoogle Scholar
  • 32 Ravn V, Rasmussen B B, Højholt L et al.. Estrogen- and progesterone receptors in normal cycling endometrium as studied by end-point titration.  Cell Tissue Res. 1994;  276(3) 419-428
    CrossrefPubMedGoogle Scholar
  • 33 Cunha G R, Cooke P S, Kurita T. Role of stromal-epithelial interactions in hormonal responses.  Arch Histol Cytol. 2004;  67(5) 417-434
    CrossrefPubMedGoogle Scholar
  • 34 Lessey B A. Two pathways of progesterone action in the human endometrium: implications for implantation and contraception.  Steroids. 2003;  68(10-13) 809-815
    CrossrefPubMedGoogle Scholar
  • 35 Anderson T L, Gorstein F, Osteen K G. Stromal-epithelial cell communication, growth factors, and tissue regulation.  Lab Invest. 1990;  62(5) 519-521
    PubMedGoogle Scholar
  • 36 Cunha G R, Young P. Role of stroma in oestrogen-induced epithelial proliferation.  Epithelial Cell Biol. 1992;  1 18-31
    PubMedGoogle Scholar
  • 37 Osteen K G, Rodgers W H, Gaire M et al.. Stromal-epithelial interaction mediates steroidal regulation of metalloproteinase expression in human endometrium.  Proc Natl Acad Sci U S A. 1994;  91(21) 10129-10133
    Google Scholar
  • 38 Giudice L C. Multifaceted roles for IGFBP-1 in human endometrium during implantation and pregnancy.  Ann N Y Acad Sci. 1997;  828 146-156
    CrossrefPubMedGoogle Scholar
  • 39 Osteen K G, Sierra-Rivera E, Keller N R, Fox D B. Interleukin-1 alpha opposes progesterone-mediated suppression of MMP-7. A possible role of this cytokine during human implantation.  Ann N Y Acad Sci. 1997;  828 137-145
    CrossrefPubMedGoogle Scholar
  • 40 Sanguansermsri D, Pongcharoen S. Pregnancy immunology: decidual immune cells.  Asian Pac J Allergy Immunol. 2008;  26(2-3) 171-181
    PubMedGoogle Scholar
  • 41 Igarashi T M, Bruner-Tran K L, Yeaman G R et al.. Reduced expression of progesterone receptor-B in the endometrium of women with endometriosis and in cocultures of endometrial cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.  Fertil Steril. 2005;  84(1) 67-74
    CrossrefPubMedGoogle Scholar
  • 42 Le T N, Johansson A. Impact of chemical warfare with agent orange on women's reproductive lives in Vietnam: a pilot study.  Reprod Health Matters. 2001;  9(18) 156-164
    CrossrefPubMedGoogle Scholar
  • 43 Heimler I, Rawlins R G, Owen H, Hutz R J. Dioxin perturbs, in a dose- and time-dependent fashion, steroid secretion, and induces apoptosis of human luteinized granulosa cells.  Endocrinology. 1998;  139(10) 4373-4379
    CrossrefPubMedGoogle Scholar
  • 44 Morán F M, VandeVoort C A, Overstreet J W, Lasley B L, Conley A J. Molecular target of endocrine disruption in human luteinizing granulosa cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin: inhibition of estradiol secretion due to decreased 17α-hydroxylase/17,20-lyase cytochrome P450 expression.  Endocrinology. 2003;  144(2) 467-473
    CrossrefPubMedGoogle Scholar
  • 45 Pocar P, Fischer B, Klonisch T, Hombach-Klonisch S. Molecular interactions of the aryl hydrocarbon receptor and its biological and toxicological relevance for reproduction.  Reproduction. 2005;  129(4) 379-389
    CrossrefPubMedGoogle Scholar
  • 46 Whitlock Jr J P. Induction of cytochrome P4501A1.  Annu Rev Pharmacol Toxicol. 1999;  39 103-125
    CrossrefPubMedGoogle Scholar
  • 47 Whitlock Jr J P, Chichester C H, Bedgood R M et al.. Induction of drug-metabolizing enzymes by dioxin.  Drug Metab Rev. 1997;  29(4) 1107-1127
    CrossrefPubMedGoogle Scholar
  • 48 Schrenk D. Impact of dioxin-type induction of drug-metabolizing enzymes on the metabolism of endo- and xenobiotics.  Biochem Pharmacol. 1998;  55(8) 1155-1162
    CrossrefPubMedGoogle Scholar
  • 49 Eskenazi B, Kimmel G. Workshop on perinatal exposure to dioxin-like compounds. II. Reproductive effects.  Environ Health Perspect. 1995;  103(Suppl 2) 143-145
    PubMedGoogle Scholar
  • 50 Rier S E, Martin D C, Bowman R E, Dmowski W P, Becker J L. Endometriosis in rhesus monkeys (Macaca mulatta) following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.  Fundam Appl Toxicol. 1993;  21(4) 433-441
    CrossrefPubMedGoogle Scholar
  • 51 Rier S E, Turner W E, Martin D C, Morris R, Lucier G W, Clark G C. Serum levels of TCDD and dioxin-like chemicals in rhesus monkeys chronically exposed to dioxin: correlation of increased serum PCB levels with endometriosis.  Toxicol Sci. 2001;  59(1) 147-159
    CrossrefPubMedGoogle Scholar
  • 52 Yang J Z, Foster W G. Continuous exposure to 2,3,7,8-tetracholordibenzo-p-dioxin inhibits the growth of surgically induced endometriosis in the ovariectomized mouse treated with high dose estradiol.  Toxicol Ind Health. 1997;  13 15-25
    PubMedGoogle Scholar
  • 53 Yang J Z, Agarwal S K, Foster W G. Subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin modulates the pathophysiology of endometriosis in the cynomolgus monkey.  Toxicol Sci. 2000;  56(2) 374-381
    CrossrefPubMedGoogle Scholar
  • 54 Cummings A M, Metcalf J L, Birnbaum L. Promotion of endometriosis by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats and mice: time-dose dependence and species comparison.  Toxicol Appl Pharmacol. 1996;  138(1) 131-139
    CrossrefPubMedGoogle Scholar
  • 55 Cummings A M, Hedge J M, Birnbaum L S. Effect of prenatal exposure to TCDD on the promotion of endometriotic lesion growth by TCDD in adult female rats and mice.  Toxicol Sci. 1999;  52(1) 45-49
    CrossrefPubMedGoogle Scholar
  • 56 Mann P C. Selected lesions of dioxin in laboratory rodents.  Toxicol Pathol. 1997;  25(1) 72-79
    CrossrefPubMedGoogle Scholar
  • 57 Safe S, Wang F, Porter W, Duan R, McDougal A. Ah receptor agonists as endocrine disruptors: antiestrogenic activity and mechanisms.  Toxicol Lett. 1998;  102–103 343-347
    PubMedGoogle Scholar
  • 58 Bofinger D P, Feng L, Chi L H et al.. Effect of TCDD exposure on CYP1A1 and CYP1B1 expression in explant cultures of human endometrium.  Toxicol Sci. 2001;  62(2) 299-314
    CrossrefPubMedGoogle Scholar
  • 59 Hayes C L, Spink D C, Spink B C, Cao J Q, Walker N J, Sutter T R. 17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1B1.  Proc Natl Acad Sci U S A. 1996;  93(18) 9776-9781
    CrossrefPubMedGoogle Scholar
  • 60 Liehr J G, Ricci M J. 4-Hydroxylation of estrogens as marker of human mammary tumors.  Proc Natl Acad Sci U S A. 1996;  93(8) 3294-3296
    CrossrefPubMedGoogle Scholar
  • 61 Bruner K L, Eisenberg E, Gorstein F, Osteen K G. Progesterone and transforming growth factor-beta coordinately regulate suppression of endometrial matrix metalloproteinases in a model of experimental endometriosis.  Steroids. 1999;  64(9) 648-653
    CrossrefPubMedGoogle Scholar
  • 62 Rodgers W H, Osteen K G, Matrisian L M, Navre M, Giudice L C, Gorstein F. Expression and localization of matrilysin, a matrix metalloproteinase, in human endometrium during the reproductive cycle.  Am J Obstet Gynecol. 1993;  168(1 Pt 1) 253-260
    PubMedGoogle Scholar
  • 63 Rodgers W H, Matrisian L M, Giudice L C et al.. Patterns of matrix metalloproteinase expression in cycling endometrium imply differential functions and regulation by steroid hormones.  J Clin Invest. 1994;  94(3) 946-953
    CrossrefPubMedGoogle Scholar
  • 64 Curry Jr T E, Osteen K G. The matrix metalloproteinase system: changes, regulation, and impact throughout the ovarian and uterine reproductive cycle.  Endocr Rev. 2003;  24(4) 428-465
    CrossrefPubMedGoogle Scholar
  • 65 Bruner K L, Matrisian L M, Rodgers W H, Gorstein F, Osteen K G. Suppression of matrix metalloproteinases inhibits establishment of ectopic lesions by human endometrium in nude mice.  J Clin Invest. 1997;  99(12) 2851-2857
    CrossrefPubMedGoogle Scholar
  • 66 Bruner K L, Rodgers W H, Gold L I et al.. Transforming growth factor beta mediates the progesterone suppression of an epithelial metalloproteinase by adjacent stroma in the human endometrium.  Proc Natl Acad Sci U S A. 1995;  92(16) 7362-7366
    CrossrefPubMedGoogle Scholar
  • 67 Sever L E, Arbuckle T E, Sweeney A. Reproductive and developmental effects of occupational pesticide exposure: the epidemiologic evidence.  Occup Med. 1997;  12(2) 305-325
    PubMedGoogle Scholar
  • 68 Gregoraszczuk E L, Zabielny E, Ochwat D. Aryl hydrocarbon receptor (AhR)-linked inhibition of luteal cell progesterone secretion in 2,3,7,8-tetrachlorodibenzo-p-dioxin treated cells.  J Physiol Pharmacol. 2001;  52(2) 303-311
    PubMedGoogle Scholar
  • 69 Miller K P, Borgeest C, Greenfeld C, Tomic D, Flaws J A. In utero effects of chemicals on reproductive tissues in females.  Toxicol Appl Pharmacol. 2004;  198(2) 111-131
    CrossrefPubMedGoogle Scholar
  • 70 Birnbaum L S, Cummings A M. Dioxins and endometriosis: a plausible hypothesis.  Environ Health Perspect. 2002;  110(1) 15-21
    CrossrefPubMedGoogle Scholar
  • 71 Anger D L, Foster W G. The link between environmental toxicant exposure and endometriosis.  Front Biosci. 2008;  13 1578-1593
    CrossrefPubMedGoogle Scholar
  • 72 Dolinoy D C, Weidman J R, Jirtle R L. Epigenetic gene regulation: linking early developmental environment to adult disease.  Reprod Toxicol. 2007;  23(3) 297-307
    CrossrefPubMedGoogle Scholar
  • 73 Tang W Y, Ho S M. Epigenetic reprogramming and imprinting in origins of disease.  Rev Endocr Metab Disord. 2007;  8(2) 173-182
    CrossrefPubMedGoogle Scholar
  • 74 Nayyar T, Bruner-Tran K L, Piestrzeniewicz-Ulanska D, Osteen K G. Developmental exposure of mice to TCDD elicits a similar uterine phenotype in adult animals as observed in women with endometriosis.  Reprod Toxicol. 2007;  23(3) 326-336
    CrossrefPubMedGoogle Scholar

Kaylon Bruner-TranPh.D. 

Women's Reproductive Health Research Center, Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine

B-1100, Medical Center North, Nashville, TN 37232-2519

Email: Kaylon.bruner-tran@vanderbilt.edu

      >