Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF ) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (338)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Skakkebæk, N.E.
Right arrow Articles by Main, K.M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Skakkebæk, N.E.
Right arrow Articles by Main, K.M.
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Reproduction, Vol. 16, No. 5, 972-978, May 2001
© 2001 European Society of Human Reproduction and Embryology

Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects: Opinion

N.E. Skakkebæk1,, E. Rajpert-De Meyts and K.M. Main

Department of Growth and Reproduction, Copenhagen University Hospital, Copenhagen, Denmark

Numerous reports have recently focused on various aspects of adverse trends in male reproductive health, such as the rising incidence of testicular cancer; low and probably declining semen quality; high and possibly increasing frequencies of undescended testis and hypospadias; and an apparently growing demand for assisted reproduction. Due to specialization in medicine and different ages at presentation of symptoms, reproductive problems used to be analysed separately by various professional groups, e.g. paediatric endocrinologists, urologists, andrologists and oncologists. This article summarizes existing evidence supporting a new concept that poor semen quality, testis cancer, undescended testis and hypospadias are symptoms of one underlying entity, the testicular dysgenesis syndrome (TDS), which may be increasingly common due to adverse environmental influences. Experimental and epidemiological studies suggest that TDS is a result of disruption of embryonal programming and gonadal development during fetal life. Therefore, we recommend that future epidemiological studies on trends in male reproductive health should not focus on one symptom only, but be more comprehensive and take all aspects of TDS into account. Otherwise, important biological information may be lost.

Key words: environmental disrupters/infertility/male reproduction/testicular cancer/testicular development

1 To whom correspondence should be addressed at: Department of Growth and Reproduction, Copenhagen University Hospital (Rigshospitalet, Section GR-5064), 9 Blegdamsvej, DK-2100 Copenhagen, Denmark. E-mail: nes{at}rh.dk


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
Hum ReprodHome page
C. Mau Kai, A. Juul, K. McElreavey, A.M. Ottesen, I.D. Garn, K.M. Main, A. Loft, N. Jorgensen, N.E. Skakkebaek, A. N. Andersen, et al.
Sons conceived by assisted reproduction techniques inherit deletions in the azoospermia factor (AZF) region of the Y chromosome and the DAZ gene copy number
Hum. Reprod., July 1, 2008; 23(7): 1669 - 1678.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
H. Leridon and R. Slama
The impact of a decline in fecundity and of pregnancy postponement on final number of children and demand for assisted reproduction technology
Hum. Reprod., June 1, 2008; 23(6): 1312 - 1319.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
F. Brucker-Davis, K. Wagner-Mahler, I. Delattre, B. Ducot, P. Ferrari, A. Bongain, J.-Y. Kurzenne, J.-C. Mas, P. Fenichel, and the Cryptorchidism Study Group from Nice Area
Cryptorchidism at birth in Nice area (France) is associated with higher prenatal exposure to PCBs and DDE, as assessed by colostrum concentrations
Hum. Reprod., May 24, 2008; (2008) den186v1.
[Abstract] [Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
K. A. McGlynn, S. M. Quraishi, B. I. Graubard, J.-P. Weber, M. V. Rubertone, and R. L. Erickson
Persistent Organochlorine Pesticides and Risk of Testicular Germ Cell Tumors
J Natl Cancer Inst, May 7, 2008; 100(9): 663 - 671.
[Abstract] [Full Text] [PDF]


Home page
J. Histochem. Cytochem.Home page
A. Wellejus, H. E. Jensen, S. Loft, and T. E. Jonassen
Expression of Aquaporin 9 in Rat Liver and Efferent Ducts of the Male Reproductive System After Neonatal Diethylstilbestrol Exposure
J. Histochem. Cytochem., May 1, 2008; 56(5): 425 - 432.
[Abstract] [Full Text] [PDF]


Home page
ReproductionHome page
D. Gunnarsson, P. Leffler, E. Ekwurtzel, G. Martinsson, K. Liu, and G. Selstam
Mono-(2-ethylhexyl) phthalate stimulates basal steroidogenesis by a cAMP-independent mechanism in mouse gonadal cells of both sexes
Reproduction, May 1, 2008; 135(5): 693 - 703.
[Abstract] [Full Text] [PDF]


Home page
BMJHome page
J. P. E. Bonde and J. Olsen
Interpreting trends in fecundity over time
BMJ, February 16, 2008; 336(7640): 339 - 340.
[Full Text] [PDF]


Home page
Biol. Reprod.Home page
G. R Hutchison, H. M Scott, M. Walker, C. McKinnell, D. Ferrara, I. K. Mahood, and R. M Sharpe
Sertoli Cell Development and Function in an Animal Model of Testicular Dysgenesis Syndrome
Biol Reprod, February 1, 2008; 78(2): 352 - 360.
[Abstract] [Full Text] [PDF]


Home page
Hum Reprod UpdateHome page
H.E. Virtanen and J. Toppari
Epidemiology and pathogenesis of cryptorchidism
Hum. Reprod. Update, January 1, 2008; 14(1): 49 - 58.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
H. Magelssen, K.K. Melve, R. Skjaerven, and S.D. Fossa
Parenthood probability and pregnancy outcome in patients with a cancer diagnosis during adolescence and young adulthood
Hum. Reprod., January 1, 2008; 23(1): 178 - 186.
[Abstract] [Full Text] [PDF]


Home page
Ann. N. Y. Acad. Sci.Home page
E. RAJPERT-DE MEYTS and C. E. HOEI-HANSEN
From Gonocytes to Testicular Cancer: The Role of Impaired Gonadal Development
Ann. N.Y. Acad. Sci., December 1, 2007; 1120(1): 168 - 180.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
A. J. Kuhl, S. M. Ross, and K. W. Gaido
CCAAT/Enhancer Binding Protein {beta}, But Not Steroidogenic Factor-1, Modulates the Phthalate-Induced Dysregulation of Rat Fetal Testicular Steroidogenesis
Endocrinology, December 1, 2007; 148(12): 5851 - 5864.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
G. M. Buck Louis, M. L. Hediger, and J. B. Pena
Intrauterine exposures and risk of endometriosis
Hum. Reprod., December 1, 2007; 22(12): 3232 - 3236.
[Abstract] [Full Text] [PDF]


Home page
J AndrolHome page
W. Dhooge, N. Van Larebeke, F. Comhaire, and J.-M. Kaufman
Reproductive Parameters of Community-Dwelling Men From 2 Regions in Flanders Are Associated With the Consumption of Self-Grown Vegetables
J Androl, November 1, 2007; 28(6): 836 - 846.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
P. A. Fowler, D. R. Abramovich, N. E. Haites, P. Cash, N. P. Groome, A. Al-Qahtani, T. J. Murray, and R. G. Lea
Human fetal testis Leydig cell disruption by exposure to the pesticide dieldrin at low concentrations
Hum. Reprod., November 1, 2007; 22(11): 2919 - 2927.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
S.M. Coutts, N. Fulton, and R.A. Anderson
Environmental toxicant-induced germ cell apoptosis in the human fetal testis
Hum. Reprod., November 1, 2007; 22(11): 2912 - 2918.
[Abstract] [Full Text] [PDF]


Home page
Hum Exp ToxicolHome page
C. Bredhult, B.-M. Backlin, and M. Olovsson
Effects of chlorinated biphenyls and metabolites on human uterine myocyte proliferation
Human and Experimental Toxicology, October 1, 2007; 26(10): 801 - 809.
[Abstract] [PDF]


Home page
Hum ReprodHome page
C. Asklund, N. Jorgensen, N.E. Skakkebaek, and T.K. Jensen
Increased frequency of reproductive health problems among fathers of boys with hypospadias
Hum. Reprod., October 1, 2007; 22(10): 2639 - 2646.
[Abstract] [Full Text] [PDF]


Home page
Hum Mol GenetHome page
M.-Y. J. Lam, J. D. Heaney, K. K. Youngren, J. H. Kawasoe, and J. H. Nadeau
Trans-generational epistasis between Dnd1Ter and other modifier genes controls susceptibility to testicular germ cell tumors
Hum. Mol. Genet., September 15, 2007; 16(18): 2233 - 2240.
[Abstract] [Full Text] [PDF]


Home page
Mol Hum ReprodHome page
A. Ferlin, E. Speltra, A. Garolla, R. Selice, D. Zuccarello, and C. Foresta
Y chromosome haplogroups and susceptibility to testicular cancer
Mol. Hum. Reprod., September 1, 2007; 13(9): 615 - 619.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
C. Giachini, F. Nuti, E. Marinari, G. Forti, and C. Krausz
Partial AZFc deletions in infertile men with cryptorchidism
Hum. Reprod., September 1, 2007; 22(9): 2398 - 2403.
[Abstract] [Full Text] [PDF]


Home page
Occup. Environ. Med.Home page
N. Olea and M. F Fernandez
Chemicals in the environment and human male fertility
Occup. Environ. Med., July 1, 2007; 64(7): 430 - 431.
[Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
R. Lambrot, H. Coffigny, C. Pairault, C. Lecureuil, R. Frydman, R. Habert, and V. Rouiller-Fabre
High Radiosensitivity of Germ Cells in Human Male Fetus
J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2632 - 2639.
[Abstract] [Full Text] [PDF]


Home page
Arch. Dis. Child.Home page
M. B Toledano and P. D Nelson
Male fertility-related disorders: cause for concern or a stalking horse?
Arch. Dis. Child., July 1, 2007; 92(7): 565 - 567.
[Full Text] [PDF]


Home page
Arch. Dis. Child.Home page
N A Abdullah, M S Pearce, L Parker, J R Wilkinson, B Jaffray, and R J Q McNally
Birth prevalence of cryptorchidism and hypospadias in northern England, 1993-2000
Arch. Dis. Child., July 1, 2007; 92(7): 576 - 579.
[Abstract] [Full Text] [PDF]


Home page
Arch. Dis. Child.Home page
N. Nassar, C. Bower, and A. Barker
Increasing prevalence of hypospadias in Western Australia, 1980-2000
Arch. Dis. Child., July 1, 2007; 92(7): 580 - 584.
[Abstract] [Full Text] [PDF]


Home page
Toxicol SciHome page
S. Plummer, R. M. Sharpe, N. Hallmark, I. K. Mahood, and C. Elcombe
Time-Dependent and Compartment-Specific Effects of In Utero Exposure to Di(n-butyl) Phthalate on Gene/Protein Expression in the Fetal Rat Testis as Revealed by Transcription Profiling and Laser Capture Microdissection
Toxicol. Sci., June 1, 2007; 97(2): 520 - 532.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
S.H. Swan, F. Liu, J.W. Overstreet, C. Brazil, and N.E. Skakkebaek
Semen quality of fertile US males in relation to their mothers' beef consumption during pregnancy
Hum. Reprod., June 1, 2007; 22(6): 1497 - 1502.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
F. S. vom Saal
Could hormone residues be involved?
Hum. Reprod., June 1, 2007; 22(6): 1503 - 1505.
[Full Text] [PDF]


Home page
EndocrinologyHome page
H. M. Scott, G. R. Hutchison, I. K. Mahood, N. Hallmark, M. Welsh, K. De Gendt, G. Verhoeven, P. O'Shaughnessy, and R. M. Sharpe
Role of Androgens in Fetal Testis Development and Dysgenesis
Endocrinology, May 1, 2007; 148(5): 2027 - 2036.
[Abstract] [Full Text] [PDF]


Home page
J AndrolHome page
N. H. Aneck-Hahn, G. W. Schulenburg, M. S. Bornman, P. Farias, and C. De Jager
Impaired Semen Quality Associated With Environmental DDT Exposure in Young Men Living in a Malaria Area in the Limpopo Province, South Africa
J Androl, May 1, 2007; 28(3): 423 - 434.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
M. Watanabe, R. Yoshida, K. Ueoka, K. Aoki, I. Sasagawa, T. Hasegawa, K. Sueoka, N. Kamatani, Y. Yoshimura, and T. Ogata
Haplotype analysis of the estrogen receptor 1 gene in male genital and reproductive abnormalities
Hum. Reprod., May 1, 2007; 22(5): 1279 - 1284.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
R. B. Jensen, S. Vielwerth, T. Larsen, G. Greisen, J. Veldhuis, and A. Juul
Pituitary-Gonadal Function in Adolescent Males Born Appropriate or Small for Gestational Age with or without Intrauterine Growth Restriction
J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1353 - 1357.
[Abstract] [Full Text] [PDF]


Home page
Mol Hum ReprodHome page
T. Tiido, A. Rignell-Hydbom, B.A.G. Jonsson, L. Rylander, A. Giwercman, and Y.L. Giwercman
Modifying effect of the AR gene trinucleotide repeats and SNPs in the AHR and AHRR genes on the association between persistent organohalogen pollutant exposure and human sperm Y : X ratio
Mol. Hum. Reprod., April 1, 2007; 13(4): 223 - 229.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
L. Carmignani, F. Gadda, G. Gazzano, G. Ragni, A. Paffoni, F. Rocco, and G. M. Colpi
Testicular sperm extraction in cancerous testicle in patients with azoospermia: A Case Report
Hum. Reprod., April 1, 2007; 22(4): 1068 - 1072.
[Abstract] [Full Text] [PDF]


Home page
ReproductionHome page
R P Amann and D N R Veeramachaneni
Cryptorchidism in common eutherian mammals
Reproduction, March 1, 2007; 133(3): 541 - 561.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
J. Merlet, C. Racine, E. Moreau, S. G. Moreno, and R. Habert
Male fetal germ cells are targets for androgens that physiologically inhibit their proliferation
PNAS, February 27, 2007; 104(9): 3615 - 3620.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
R.I. McLachlan, E. Rajpert-De Meyts, C.E. Hoei-Hansen, D.M. de Kretser, and N.E. Skakkebaek
Histological evaluation of the human testis--approaches to optimizing the clinical value of the assessment: Mini Review
Hum. Reprod., January 1, 2007; 22(1): 2 - 16.
[Abstract] [Full Text] [PDF]


Home page
J AndrolHome page
J. Y. Polsky, K. J. Aronson, J. P. W. Heaton, and M. A. Adams
Pesticides and Polychlorinated Biphenyls as Potential Risk Factors for Erectile Dysfunction
J Androl, January 1, 2007; 28(1): 28 - 37.
[Abstract] [Full Text] [PDF]


Home page
J AndrolHome page
R. Radpour, M. Rezaee, A. Tavasoly, S. Solati, and A. Saleki
Association of Long Polyglycine Tracts (GGN Repeats) in Exon 1 of the Androgen Receptor Gene With Cryptorchidism and Penile Hypospadias in Iranian Patients
J Androl, January 1, 2007; 28(1): 164 - 169.
[Abstract] [Full Text] [PDF]


Home page
ReproductionHome page
B. Aflatoonian and H. Moore
Germ cells from mouse and human embryonic stem cells.
Reproduction, November 1, 2006; 132(5): 699 - 707.
[Abstract] [Full Text] [PDF]


Home page
Eur J EndocrinolHome page
K. M Main, J. Toppari, and N. E Skakkebaek
Gonadal development and reproductive hormones in infant boys
Eur. J. Endocrinol., November 1, 2006; 155(suppl_1): S51 - S57.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
D. Ferrara, N. Hallmark, H. Scott, R. Brown, C. McKinnell, I. K. Mahood, and R. M. Sharpe
Acute and Long-Term Effects of in Utero Exposure of Rats to Di(n-Butyl) Phthalate on Testicular Germ Cell Development and Proliferation
Endocrinology, November 1, 2006; 147(11): 5352 - 5362.
[Abstract] [Full Text] [PDF]


Home page
PediatricsHome page
P. J. Landrigan, L. Trasande, L. E. Thorpe, C. Gwynn, P. J. Lioy, M. E. D'Alton, H. S. Lipkind, J. Swanson, P. D. Wadhwa, E. B. Clark, et al.
The National Children's Study: A 21-Year Prospective Study of 100 000 American Children
Pediatrics, November 1, 2006; 118(5): 2173 - 2186.
[Abstract] [Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
K. A. McGlynn, Y. Zhang, L. C. Sakoda, M. V. Rubertone, R. L. Erickson, and B. I. Graubard
Maternal smoking and testicular germ cell tumors.
Cancer Epidemiol. Biomarkers Prev., October 1, 2006; 15(10): 1820 - 1824.
[Abstract] [Full Text] [PDF]


Home page
ReproductionHome page
G. Delbes, C. Levacher, and R. Habert
Estrogen effects on fetal and neonatal testicular development.
Reproduction, October 1, 2006; 132(4): 527 - 538.
[Abstract] [Full Text] [PDF]


Home page
Ann. N. Y. Acad. Sci.Home page
E. M WARD, M. J THUN, L. M HANNAN, and A. JEMAL
Interpreting cancer trends.
Ann. N.Y. Acad. Sci., September 1, 2006; 1076: 29 - 53.
[Abstract] [Full Text] [PDF]


Home page
Toxicol Ind HealthHome page
N. Chamkhia, M. Sakly, and K. B. Rhouma
Male reproductive impacts of styrene in rat.
Toxicology and Industrial Health, September 1, 2006; 22(8): 349 - 355.
[Abstract] [PDF]


Home page
Endocr. Rev.Home page
M. Cools, S. L. S. Drop, K. P. Wolffenbuttel, J. W. Oosterhuis, and L. H. J. Looijenga
Germ Cell Tumors in the Intersex Gonad: Old Paths, New Directions, Moving Frontiers
Endocr. Rev., August 1, 2006; 27(5): 468 - 484.
[Abstract] [Full Text] [PDF]


Home page
Arch. Dis. Child.Home page
C L Acerini and I A Hughes
Endocrine disrupting chemicals: a new and emerging public health problem?
Arch. Dis. Child., August 1, 2006; 91(8): 633 - 641.
[Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
R. M. Sharpe
Perinatal Determinants of Adult Testis Size and Function.
J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2503 - 2505.
[Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
K. M. Main, J. Toppari, A.-M. Suomi, M. Kaleva, M. Chellakooty, I. M. Schmidt, H. E. Virtanen, K. A. Boisen, C. M. Kai, I. N. Damgaard, et al.
Larger Testes and Higher Inhibin B Levels in Finnish than in Danish Newborn Boys
J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2732 - 2737.
[Abstract] [Full Text] [PDF]


Home page
Hum Reprod UpdateHome page
L. Aksglaede, A. Juul, H. Leffers, N. E. Skakkebaek, and A.-M. Andersson
The sensitivity of the child to sex steroids: possible impact of exogenous estrogens
Hum. Reprod. Update, July 1, 2006; 12(4): 341 - 349.
[Abstract] [Full Text] [PDF]


Home page
Mol Hum ReprodHome page
A. Ferlin, N.V. Bogatcheva, L. Gianesello, A. Pepe, C. Vinanzi, A.I. Agoulnik, and C. Foresta
Insulin-like factor 3 gene mutations in testicular dysgenesis syndrome: clinical and functional characterization
Mol. Hum. Reprod., June 1, 2006; 12(6): 401 - 406.
[Abstract] [Full Text] [PDF]


Home page
Int J EpidemiolHome page
K. A McGlynn, B. I Graubard, M. A Klebanoff, and M. P Longnecker
Risk factors for cryptorchism among populations at differing risks of testicular cancer
Int. J. Epidemiol., June 1, 2006; 35(3): 787 - 795.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
N. Jorgensen, A. K. Bang, E. Carlsen, M. Holm, J. H. Petersen, and N. E. Skakkebaek
Reply: A study of finger lengths, semen quality and sex hormones in 360 young men from the general Danish population
Hum. Reprod., May 1, 2006; 21(5): 1331 - 1332.
[Full Text] [PDF]


Home page
Hum Reprod UpdateHome page
E. Rajpert-De Meyts
Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects
Hum. Reprod. Update, May 1, 2006; 12(3): 303 - 323.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
L. R. Fraser, E. Beyret, S. R. Milligan, and S. A. Adeoya-Osiguwa
Effects of estrogenic xenobiotics on human and mouse spermatozoa
Hum. Reprod., May 1, 2006; 21(5): 1184 - 1193.
[Abstract] [Full Text] [PDF]