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
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
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|
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|
|
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|
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|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
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|
|
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|
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|
|
|
|
|
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|
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|
|
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|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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]
|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
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|
 |
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 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]
|
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|
|
|
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