An immunohistochemical analysis of the effects of androgen receptor knock out on gubernacular differentiation in the mouse.

AIM: Cryptorchidism affects 2%-4% of newborn boys and causes infertility and cancer. While normal androgen function is required for successful inguinoscrotal descent, its exact role on gubernacular morphology remains unidentified. We aimed to decipher the effect of androgen blockade on the gubernaculum and surrounding structures.

METHODS

Genetically modified mice with androgen receptor knock out (ARKO) were sectioned at ages E17, D0, and D2 for immunohistochemical analysis and D4 for morphological analysis (with ethical approval; A644). Mutants and control littermates were labeled with Ki67, Desmin, and Pax7 to identify the degree of gubernaculuar eversion and the composition of the growth center in the gubernaculum, using light or confocal microscopy.

RESULTS

Androgen blockade prevented gubernacular eversion in all animals aged between E17 and D2 when compared to wild types. Furthermore, a growth center was visible, as indicated by a 'swirl' of immature fibroblasts, in D2 animals but was absent in ARKO mice. Moreover, the gubernacular cord was seen to increase in ARKO mice when compared to wild types and increased in size with age. There were no labeling differences in the antibodies tested for gubernacular differentiation.

CONCLUSION

Gubernacular eversion in rodents prior to inguinoscrotal migration was androgen dependent, as well as maintenance of gubernacular cord length. This study shows that androgen blockade causes cryptorchidism in mice by preventing gubernacular eversion and possibly by preventing shortening of the gubernacular cord. Altering the morphology of the gubernaculum in response to androgen clearly contributes to the clinical problem of cryptorchidism.