Testicular Dysgenesis Syndrome (TDS)

  • Manuel Nistal
  • Pilar González-Peramato
  • Álvaro Serrano
Chapter
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Abstract

In recent decades, epidemiological evidence of an increase of certain diseases of the male reproductive tract, such as testicular germ cell tumors, cryptorchidism, infertility, and hypospadias in industrialized countries, has suggested the hypothesis of the presence of a common testicular abnormality for which the name of testicular dysgenesis syndrome has been proposed. Studies have been routed in several lines of research: (a) identify the factors (endocrine disruptors) that promote the onset of these diseases, (b) specify the cellular mechanisms through which these factors act altering the fetal physiology, and (c) identify testicular lesions they produce what, although in varying degrees, might be common to all four pathologies. After a summary of the incidence of various pathologies and the most frequent endocrine disruptors that affect testicular physiology, this chapter also exposes the testicular histological findings (mixed atrophy, hypoplastic tubules, Sertoli cell nodules, granular changes in Sertoli cells, tubules with germ cell hypoplasia, microlithiasis, focal Leydig cell hyperplasia, and germ cell neoplasia in situ) that enable to suggest that a patient has a testicular dysgenesis syndrome.

Keywords

Sertoli Cell Leydig Cell Testicular Cancer Endocrine Disruptor Undescended Testicle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. 1.
    Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Evidence for decreasing quality of semen during past 50 years. BMJ. 1992;305:609–13.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Jouannet P, Wang C, Eustache F, Kold-Jensen T, Auger J. Semen quality and male reproductive health: the controversy about human sperm concentration decline. APMIS. 2001;109:333–44.CrossRefPubMedGoogle Scholar
  3. 3.
    Nohynek GJ, Borgert CJ, Dietrich D, Rozman KK. Endocrine disruption: fact or urban legend? Toxicol Lett. 2013;223:295–305.CrossRefPubMedGoogle Scholar
  4. 4.
    Skakkebaek NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod. 2001;6:972–8.CrossRefGoogle Scholar
  5. 5.
    Rosen A, Jayram G, Drazer M, Eggener SE. Global trends in testicular cancer incidence and mortality. Eur Urol. 2011;60:374–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Skakkebaek NE, Rajpert-De Meyts E, Buck Louis GM, Toppari J, Andersson AM, Eisenberg ML, Jensen TK, Jørgensen N, Swan SH, Sapra KJ, Ziebe S, Priskorn L, Juul A. Male reproductive disorders and fertility trends: influences of environment and genetic susceptibility. Physiol Rev. 2016;96:55–97.CrossRefPubMedGoogle Scholar
  7. 7.
    Petersen PM, Giwercman A, Hansen SW, Berthelsen JG, Daugaard G, Rørth M, Skakkebaek NE. Impaired testicular function in patients with carcinoma-in-situ of the testis. J Clin Oncol. 1999;17:173–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Rajpert-De Meyts E. Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects. Hum Reprod Update. 2006;12:303–23.CrossRefPubMedGoogle Scholar
  9. 9.
    Boisen KA, Kaleva M, Main KM, Virtanen HE, Haavisto AM, Schmidt IM, Chellakooty M, Damgaard IN, Mau C, Reunanen M, Skakkebæk NE, Toppari J. Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries. Lancet. 2004;363:1264–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Ward B, Hunter WM. The absent testicle, a report on a survey carried outamong schoolboys in Nottingham. Br Med J. 1960;1:1110.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Pettersson A, Richiardi L, Nordenskjold A, Kaijser M, Akre O. Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med. 2007;356:1835–41.CrossRefPubMedGoogle Scholar
  12. 12.
    Dieckmann KP, Pichlmeier U. Clinical epidemiology of testicular germ cell tumors. World J Urol. 2004;22:2–14.CrossRefPubMedGoogle Scholar
  13. 13.
    Paulozzi LJ, Erickson JD, Jackson RJ. Hypospadias trends in two US surveillance systems. Pediatrics. 1997;100:831–4.CrossRefPubMedGoogle Scholar
  14. 14.
    Paulozzi LJ. International trends in rates of hypospadias and cryptorchidism. Environ Health Perspect. 1999;107:297–302.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Bergström R, Adami HO, Möhner M, Zatonski W, Storm H, Ekbom A, Tretli S, Teppo L, Akre O, Hakulinen T. Increase in testicular cancer incidence in six European countries: a birth cohort phenomenon. J Natl Cancer Inst. 1996;88:727–33.CrossRefPubMedGoogle Scholar
  16. 16.
    Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Declining semen quality and increasing incidence of testicular cancer: is there a common cause? Environ Health Perspect. 1995;103(Suppl 7):137–9.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Khuri FJ, Hardy BE, Churchill BM. Urologic anomalies associated with hypospadias. Urol Clin North Am. 1981;8:565–71.PubMedGoogle Scholar
  18. 18.
    Ge RS, Chen GR, Tanrikut C, Hardy MP. Phthalate ester toxicity in Leydig cells: developmental timing and dosage considerations. Reprod Toxicol. 2007;23:366–73.CrossRefPubMedGoogle Scholar
  19. 19.
    Splingart C, Frapsauce C, Veau S, Barthélémy C, Royère D, Guérif F. Semen variation in a population of fertile donors: evaluation in a French centre over a 34-year period. Int J Androl. 2012;35:467–74.CrossRefPubMedGoogle Scholar
  20. 20.
    Sharpe RM. The ‘oestrogen hypothesis’- where do we stand now? Int J Androl. 2003;26:2–15.CrossRefPubMedGoogle Scholar
  21. 21.
    Dallinga JW, Moonen EJ, Dumoulin JC, Evers JL, Geraedts JP, Kleinjans JC. Decreased human semen quality and organochlorine compounds in blood. Hum Reprod. 2002;17:1973–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Palmer JR, Herbst AL, Noller KL, Boggs DA, Troisi R, Titus-Ernstoff L, Hatch EE, Wise LA, Strohsnitter WC, Hoover RN. Urogenital abnormalities in men exposed to diethylstilbestrol in utero: a cohort study. Environ Health. 2009;8:37.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Rebourcet D, O’Shaughnessy PJ, Monteiro A, Milne L, Cruickshanks L, Jeffrey N, Guillou F, Freeman TC, Mitchell RT, Smith LB. Sertoli cells maintain Leydig cell number and peritubular myoid cell activity in the adult mouse testis. PLoS One. 2014;9:e105687.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Petersen JH, Breindahl T. Plasticizers in total diet samples, baby food and infant formulae. Food Addit Contam. 2000;17:133–41.CrossRefPubMedGoogle Scholar
  25. 25.
    Parks LG, Ostby JS, Lambright CR, Abbott BD, Klinefelter GR, Barlow NJ, Gray Jr LE. The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol Sci. 2000;58:339–49.CrossRefPubMedGoogle Scholar
  26. 26.
    Adham IM, Emmen JM, Engel W. The role of the testicular factor INSL3 in establishing the gonadal position. Mol Cell Endocrinol. 2000;160:11–6.CrossRefPubMedGoogle Scholar
  27. 27.
    Scott HM, Hutchison GR, Jobling MS, McKinnell C, Drake AJ, Sharpe RM. Relationship between androgen action in the “male programming window”, fetal Sertoli cell number, and adult testis size in the rat. Endocrinology. 2008;149:5280–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Li L, Bu T, Su H, Chen Z, Liang Y, Zhang G, Zhu D, Shan Y, Xu R, Hu Y, Li J, Hu G, Lian Q, Ge RS. Inutero exposure to diisononyl phthalate caused testicular dysgenesis of rat fetal testis. Toxicol Lett. 2015;232:466–74.CrossRefPubMedGoogle Scholar
  29. 29.
    Kilcoyne KR, Smith LB, Atanassova N, Macpherson S, McKinnell C, van den Driesche S, Jobling MS, Chambers TJ, De Gendt K, Verhoeven G, O’Hara L, Platts S, Renato de Franca L, Lara NL, Anderson RA, Sharpe RM. Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells. Proc Natl Acad Sci U S A. 2014;111:E1924–32.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Brouwers MM, Feitz WF, Roelofs LA, Kiemeney LA, de Gier RP, Roeleveld N. Hypospadias: a transgenerational effect of diethylstilbestrol? Hum Reprod. 2006;21:666–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Nistal M, Gonzalez-Peramato P, De Miguel MP. Sertoli cell dedifferentiation in human cryptorchidism and gender reassignment shows similarities between fetal environmental and adult medical treatment estrogen and antiandrogen exposure. Reprod Toxicol. 2013;42:172–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Nistal M, Garcia-Rodeja E, Paniagua R. Granular transformation of Sertoli cells in testicular disorders. Hum Pathol. 1991;22:131–7.CrossRefPubMedGoogle Scholar
  33. 33.
    Nistal M, Regadera J, Winitzky P, Tejerina E, Chemes H. Granular changes in Sertoli cells in children and pubertal patients. Fertil Steril. 2005;83:1489–99.CrossRefPubMedGoogle Scholar
  34. 34.
    Holm M, Rajpert-De Meyts E, Andersson AM, Skakkebaek NE. Leydig cell micronodules are a common finding in testicular biopsies from men with impaired spermatogenesis and are associated with decreased testosterone/LH ratio. J Pathol. 2003;199:378–86.CrossRefPubMedGoogle Scholar
  35. 35.
    Andersson AM, Jørgensen N, Frydelund-Larsen L, Rajpert-De Meyts E, Skakkebaek NE. Impaired Leydig cell function in infertile men: a study of 357 idiopathic infertile men and 318 proven fertile controls. J Clin Endocrinol Metab. 2004;89:3161–7.CrossRefPubMedGoogle Scholar
  36. 36.
    Juul A, Almstrup K, Andersson AM, Jensen TK, Jørgensen N, Main KM, Rajpert-De Meyts E, Toppari J, Skakkebæk NE. Possible fetal determinants of male infertility. Nat Rev Endocrinol. 2014;10:553–62.CrossRefPubMedGoogle Scholar
  37. 37.
    Nistal M, Gonzalez-Peramato P, Regadera J, Serrano A, Tarin V, De Miguel MP. Primary testicular lesions are associated with testicular germ cell tumors of adult men. Am J Surg Pathol. 2006;30:1260–8.CrossRefPubMedGoogle Scholar
  38. 38.
    Hoei-Hansen CE, Holm M, Rajpert-De Meyts E, Skakkebaek NE. Histological evidence of testicular dysgenesis in contralateral biopsies from 218 patients with testicular germ cell cancer. J Pathol. 2003;200:370–4.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Manuel Nistal
    • 1
  • Pilar González-Peramato
    • 2
  • Álvaro Serrano
    • 3
  1. 1.Universidad Autónoma de Madrid (UAM)Department of Anatomy, Histology and Neuroscience, School of MedicineMadridSpain
  2. 2.School of Medicine, Universidad Autónoma de Madrid (UAM), University Hospital La Paz, Department of PathologyMadridSpain
  3. 3.University Hospital Clinico San Carlos, Department of UrologyMadridSpain

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