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Endocrine Abstracts (2008) 15 S3

Society for Endocrinology Asia and Oceania Medal Lecture

Testicular dysgenesis syndrome: clinical and environmental aspects

Niels Skakkebaek

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University of Copenhagen, Copenhagen, Denmark.


Recent research in male reproductive disorders has revealed that testicular germ cell cancer, undescended testis, poor semen quality and hypospadias may be biologically linked as a testicular dysgenesis syndrome (TDS). The evidence comes from a number of clinical, epidemiological and experimental animal studies, which are in line with the hypothesis that these disorders are of fetal origin. Core evidence comes from studies of the precursor to testicular germ cell cancer – the carcinoma in situ cell -, which is assumed to be a transformed gonocyte, arrested during the fetal differentiation process. The factors involved remain to be determined, but impaired Sertoli- and Leydig cell functions may be involved. The most severe cases of TDS may be due to rare genetic or chromosomal disorders, e.g. SRY mutations or 45,X/46,XY karyotype. However, the bulk of TDS cases may be due to environmental factors. Recently, a rat model for a TDS-like syndrome was described in offspring exposed in utero to certain phthalates. However, humans are exposed to much smaller doses of phthalates and human exposures are never limited to one or two endocrine disrupters. Our food, water, air and cosmetics contain mixtures of a high number of agents, which individually may be present in tiny amounts, but nevertheless may constitute a risk, particularly during the most sensitive periods, which we believe are the fetal period and childhood. We speculate that some of the endocrine disrupters may be responsible for the increase in TDS related symptoms, at least in Caucasian populations. The quantitative role of TDS for male reproductive health in general remains to be determined. Obviously there are several etiologies to male infertility, including genetic factors and men with isolated hypospadias without other genital abnormalities may have semen quality similar to men in the general population. However, most cases of testicular maldescent and perhaps all cases of testicular germ cell cancer may be due to testicular dysgenesis1,2.

Reference

1. Skakkebæk NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Human Reproduction 2001 16 972–978.

2. Skakkebæk NE, Jørgensen N, Main KM, Rajpert-De Meyts E, Leffers H, Andersson A-M et al. Is human fecundity declining? Internationl Journal of Andrology 2006 29 2–11.

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