Undescended testis (UDT) is a major health problem, affecting over 2% of new-born boys with increased infertility (30-60%) and testicular cancer (5-10 fold higher than normal males) later in life. We have studied animal models in conjunction with human biopsies of UDT in order to understand the process of gonocyte transformation into SSC to elucidate how to prevent infertility and testicular cancer in cryptorchidism.
We used testes from Oct4-promoter-driving GFP transgenic mice, androgen receptor knockout (ARKO) mice and human biopsies for gene expression with real-time PCR and immunohistochemistry with antibody labelling followed by confocal imaging analysis. Serum and testes were collected from C57Bl/6 male mice for hormone analysis to examine mouse minipuberty.
We have found that mouse gonocyte (Oct4+/C-Kit-) transformed into SSC (Oct4+/C-Kit+) between postnatal days 2-6. SSC further develop into Oct4-/C-Kit+ and Oct4-/C-Kit-/ germ cells. Interestingly, we found that there was transient testosterone surge at postnatal day 1-3 and gene expression of both FSH receptor and Oct4 peaked at postnatal day 3-6 in mouse. We also found that there were no difference for number of gonocytes transformed into SSC/tubule between ARKO mice and wild type littermates. Confocal image analysis on UDT biopsies showed that percentage of tubules with VASA- germ cells significantly decreased whereas number of empty tubules without germ cells significantly increased with increasing age of orchidopexy.
In conclusion, we found that gonocyte transformation into SSC at 2-6 days of age. Like the human minipuberty does exist in mouse and coincides with the gonocyte transformation into SSC. Gonocyte transformation in mouse is independent from androgen. Orchidopexy at older age showed significant germ cell depletion. Our results suggest that FSH or/and non-androgenic factors may play important role in gonocyte transformation into SSC.