Germ cell cancer and disorders of spermatogenesis: an environmental connection?
Why is there a small peak of germ cell tumours in the postnatal period and a major peak in young age, starting at puberty? And, paradoxically, small risk in old age, although spermatogenesis is a lifelong process? Why is this type of cancer more common in individuals with maldeveloped gonads, including undescended testis, gonadal dysgenesis and androgen insensitivity syndrome? Why has there, during the past 50 years, been a quite dramatic increase in testicular cancer in many developed countries? These are just a few of many questions concerning testicular cancer. However, the recent progress in research in the early stages of testicular cancer (carcinoma in situ testis (CIS)) allows us to begin to answer some of these questions. There is more and more evidence that the CIS cell is a gonocyte with stem cell potential, which explains why an adult man can develop a non-seminoma, which is a neoplastic caricature of embryonic growth. We consider the possibility that CIS cells may loose their stem cell potential with ageing. Along these lines, a seminoma is regarded a gonocytoma where the single gonocytes have little or no stem cell potential. The Sertoli and Leydig cells, which are activated postnatally and during and after puberty, may play a crucial role for both the development of the CIS gonocyte and progression of the neoplasm to invasiveness. The reported increase in testicular cancer is not the only sign that male reproductive health is at risk. There are reports that undescended testis and hypospadias have become more common. Also semen quality has deteriorated, at least in some countries. The epidemiological evidence suggests that environmental factors may play a role. Are the environmental hormone disrupters (e.g. DDT, PCB, nonylphenol, bisphenol A) to be blamed for the apparently synchronised deterioration in these aspects of male reproductive health?
Skakkebaek
N E
NE
University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark.
Rajpert-De Meyts
E
E
Jørgensen
N
N
Carlsen
E
E
Petersen
P M
PM
Giwercman
A
A
Andersen
A G
AG
Jensen
T K
TK
Andersson
A M
AM
Müller
J
J
D000328:Adult; D000367:Age Factors; D004781:Environmental Exposure / Q000009:adverse effects; D018237:Germinoma / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D013091:Spermatogenesis; D013736:Testicular Neoplasms / Q000209:etiology / Q000473:pathology / Q000503:physiopathology