The tumor suppressor protein p53 participates in normal cell differentiatio
n as well as induction of programmed cell death. The authors investigated t
he effect of p53 overexpression on spermatogenesis by transferring p53 gene
into the rat testes. Replication-deficient recombinant adenovirus vectors
were constructed to include cytomegalovirus (CMV) promoter driving wild-typ
e p53 (Ad-CMV-p53) or beta -galactosidase (Ad-CMV-beta -gal). Virus was del
ivered to cells of the tubules by slow retrograde injection through the ret
e testis. At 0, 4. 7, and 14 days, testes were removed, weighed, and analyz
ed histopathologically, including immunohistochemistry for p53, Bcl-2. Bar.
and interleukin-1 beta converting enzyme (ICE). Testicular weight was decr
eased in Ad-CMV-p53 group at 14 days after injection. while no change occur
red in phosphate-buffered saline-injected controls or Ad-CMV-beta -gal-infe
cted testes. Beyond 4 days, cell degradation in tubules interfered with imm
unohistochemical observation in the Ad-CMV-p53 group. At 4 days, p53 was ex
pressed mostly in spermatocytes. Bar showed greater expression in the p53 g
roup than in the control or Ad-CMV-beta -gal group. ICE, expressed mostly i
n spermatids. was more abundant in the p33 group than in controls. Overall,
p53 overexpression in the testis impaired spermatogenesis.