Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects by N.E. Skakkebaek et al., Human Reproduction (5):972-978, Jul 2001
Key Papers from the University of Ottawa R. Samuel McLaughlin Centre for Population Health Risk Assessment
In this paper Dr. Neils Skakkebaek and colleagues bring forward the evidence for a synchronized increase between countries in male reproductive problems such as testicular cancer, reduced semen quality and genital tract abnormalities. To date poor semen quality, an increasing incidence of testicular cancer, undescended testis (cryptorchidism) and hypospadias have been treated as separate disorders. However, Dr. Neils Skakkebaek and his colleagues at Copenhagen University Hospital believe that the association of male reproductive problems reflects the existence of a common underlying entity they call the Testicular Dysgenesis Syndrome (TDS) resulting in maldeveloped testes. The present article discusses data from animal studies and human investigations and the possible role of endocrine disruptors in the etiology of TDS.
Scientific evidence has associated high risks of testicular cancer, hypospadias, and cryptorchidism with certain rare genetic abnormalities which result in testicular dysgenesis. In addition, certain degrees of testicular maldevelopment have been observed in a large fraction of men with testicular cancer and cryptorchidism. Numerous studies have provided evidence which links testicular cancer and impaired spermatogenesis. It has been shown that men with testicular cancer often present with very low sperm counts and have significantly fewer offspring than healthy controls prior to tumor development. The authors propose that future epidemiological studies on trends in male reproductive health should take into account all aspects of TDS, otherwise vital biological information may be lost.
Animal studies have provided an insight into how prenatal exposure to exogenous estrogens and anti-androgens might result in low sperm counts, hypospadias, undescended testis or testicular cancer. For example, elevated estrogen levels in the womb have been shown to suppress the secretion of follicle-stimulating hormone thereby inhibiting the multiplication of Sertoli cells. The number of Sertoli cells formed in the critical period of development fixes sperm output in adult life; therefore, fewer Sertoli cells result in a lower sperm count. In addition, Sertoli cells regulate the descent of testes, masculinization of the reproductive tract, and the development of the urethra. Within the developing testes, these cells regulate cell division and abnormalities in this process are thought to give rise to testicular cancer.
Declines in populations of wildlife species that have been associated with reproductive effects of endocrine-disrupting environmental contaminants suggest that persistent endocrine disruptors may also have adverse effects on humans. Biological and epidemiological studies suggest that abnormalities in the male reproductive system can result from disruption in embryonic programming and development of sex organs in the fetus. Adverse environmental factors, perhaps acting on genetic susceptibility, could be to blame. In particular, increased exposure to environmental estrogens and antiandrogens in the womb has been suggested to be responsible for falling sperm counts and increased reproductive abnormalities in men. There is evidence that some natural and manmade chemicals are capable of impacting human reproductive systems. However, few chemicals have been examined for their possible hormone activity and impact on humans.