Adenoviral-mediated HGF expression inhibits germ cell apoptosis in rats with cryptorchidism.
BACKGROUND
Prior studies have shown that the hepatocyte growth factor (HGF), as known for its multiple biological effects, possibly regulates spermatogenesis or tubulogenesis in the testis. To clarify the effect of HGF on restoration of spermatogenesis, or testicular weight, we transferred the HGF gene into the testis of the rat experimental cryptorchid model.


METHODS
Replication-deficient recombinant adenoviral vectors containing the CAG promoter driving rat HGF (pAxCAHGF) and LacZ (pAxCALacZ) were constructed. Sprague-Dawley rats surgically induced with unilateral cryptorchidism and subsequent orchidopexy were divided into three groups: control (PBS), pAxCALacZ and pAxCAHGF by intratesticular injection. At 2 and 4 weeks after subsequent orchidopexy, testes were removed and weighed. These specimens were analyzed histopathologically, and examined for cell apoptosis. HGF expression in these specimens associated with c-Met receptor-mediated signal molecules was examined by reverse transcription-polymerase chain reaction (RT-PCR), Western blot or immunohistochemical study.


RESULTS
Adenovirus-mediated HGF gene transfer induced overexpression of HGF in some seminiferous epithelial cells and interstitial cells, increased the phosphorylation of ERK and Akt, and decreased numbers of apoptotic cells of germ cells. HGF transduction also significantly increased the numbers of germ cells and testicular weight by 4 weeks compared with the other control groups.


CONCLUSIONS
Adenoviral-mediated HGF gene transfer into the testis in the cryptorchidism rats inhibited germ cell apoptosis and restored spermatogenesis.
Department of Urology, Kobe University School of Medicine, Kobe, Japan.
Kazumasa
K
Goda
Masato
M
Fujisawa
Toshiro
T
Shirakawa
Masaki
M
Dobashi
Goshi
G
Shiota
Zhu Jun
ZJ
Zhang
Akinobu
A
Gotoh
Sadao
S
Kamidono
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D003456:Cryptorchidism / Q000473:pathology*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D005854:Germ Cells / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009929:Organ Size; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013091:Spermatogenesis; D013737:Testis / Q000473:pathology*
D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met