Germ cell atypia in undescended testes hinges on the aetiology of cryptorchidism but not the abdominal location per se

Abstract

Testicular carcinoma in situ (CIS), which precedes germ cell tumours, has been associated with coexistence or a history of testicular maldescent in 20-30% of human cases. The objective of this study was to determine if the abdominal location of the testis by itself affects differentiation of germ cells and why only some undescended testes manifest atypical germ cells. Groups (n = 4-6) of pregnant Dutch-Belted rabbits were treated on alternate days between gestation days 15 and 30 with anti-androgenic chemicals - p,p′ 1,1-dichloro-2,2- bis(p-chlorophenyl)ethylene (DDE; 100 mg/kg bw; oral), or flutamide (50 mg/kg; s.c.); oestrogenic chemical octylphenol (150 mg/kg; oral); or nothing. Groups (n = 4) of neonatal male pups from untreated litters were either implanted with oestradiol (0.5 mg; 60-day release), surgically rendered cryptorchid before testes transcended inguinal canal, or left untreated. Of the pups exposed in utero, four of the 12 DDE, two of the nine flutamide and one of the four octylphenol pups were unilaterally cryptorchid. All animals treated with oestradiol were bilaterally cryptorchid. Light and electron microscopic evaluation at 24-26 weeks revealed presence of atypical germ cells in the undescended testes of DDE-, octylphenol-, and oestradiol-exposed animals but not in flutamide-treated or surgical cryptorchids. These atypical cells exhibited morphological hallmarks of CIS, which included large nuclei with irregular contours, meandering nucleoli, swollen mitochondria, unusual cytoplasmic inclusions and occasional mitotic figures. As transformation of germ cells to CIS-like cells did not occur in flutamide or surgical groups, this phenomenon seems to be directly associated with the type of the chemical assault but not with the abdominal location of the testis per se. © 2005 Blackwell Publishing Ltd.