Do environmental factors play a role in the aetiology of carcinoma in situ testis and the testicular dysgenesis syndrome?
The hypothesis of the Testicular Dysgenesis Syndrome (TDS), first suggested in 2001, propose that several disorders of the male reproductive system such as infertility, hypospadias, cryptorchidism and testicular cancer are all symptoms of TDS, which is most likely initiated during early foetal development, and may be provoked by external factors such as endocrine disruptors in addition to genetic predisposition. Testicular germ cell tumours (TGCTs), considered the most severe symptom of TDS, have increased in incidence during the last 60 years, to become the most common malignancy in young Caucasian men aged 17-45 years. TGCTs of young men originate from carcinoma in situ (CIS) cells. In the last few years, progress has been made identifying candidate genes involved in the neoplastic development of CIS, which may elucidate the timing of the initiation of CIS, currently thought to originate in foetal life from primordial germ cells or early gonocytes. Histological dysgenetic features are frequently seen in testes affected with the TDS components testis cancer or cryptorchidism. A TDS-like phenotype can be induced in male rats by in utero exposure to high concentrations of dibutyl phthalate (DBP) suggesting that ubiquitously present environmental endocrine disruptors may play a role in the aetiology of human TDS. So far, no animal model has been able to mimick all the symptoms of TDS including TGCTs although CIS-like cells have been found in a spontaneous testicular neoplasm in a rabbit.
Sonne
S B
SB
University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark.
Hoei-Hansen
C E
CE
Fisher
J S
JS
Leffers
H
H
Rajpert-de Meyts
E
E
Skakkebaek
N E
NE
D000293:Adolescent; D000328:Adult; D002278:Carcinoma in Situ / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D002869:Chromosome Aberrations; D006059:Gonadal Dysgenesis / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011123:Polyploidy; D013733:Testicular Diseases / Q000473:pathology*; D013736:Testicular Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology*