APOPTOSIS IN THE RAT PENIS AFTER PENILE DENERVATION

Purpose: Despite the advances in nerve sparing prostatectomy for prost ate cancer, some patients develop impotence or subjectively complain o f a decrease in penile size. We hypothesized that these clinical obser vations may be explained by injury to the cavernous nerves resulting i n programmed cell death (apoptosis) within the penis. We utilized a ra t model of penile denervation in order to demonstrate apoptosis after denervation. Methods and Materials: Fifteen male Sprague Dawley rats u nderwent abdominal exploration and bilateral cavernous neurotomy. Fift een sham operations were performed as normal controls. The rats were s acrificed on postoperative day 1, 2, 3, 6, and 10 and their penises we re harvested. Messenger RNA was extracted and probed on a northern blo t for sulfated glycoprotein-2 (SGP-2). SGP-2 is a gene product reporte d to be elevated in apoptotic tissues. Separate denervated and sham ra ts were used for DNA extraction (sacrificed postoperative day #2) in o rder to demonstrate the internucleosomal DNA fragmentation (laddering) found in apoptotic tissues. In addition, in situ histology was perfor med with ISEL techniques (in situ end labelling) to stain for apoptoti c nuclei in denervated rats. Results: Northern blot analysis showed a large increase in SGP-2 mRNA expression in the denervated rats with li ttle detected in the sham operated group. DNA extraction studies revea led the presence of internucleosomal DNA fragmentation on agarose gel (a marker for apoptosis) in the denervated group versus intact high mo lecular weight DNA in the sham rats. In addition, in situ staining of denervated penile erectile tissue demonstrated apoptotic nuclei in the cavernous tissue. Conclusion: Apoptosis of penile erectile tissue occ urs after denervation of the rat penis. This has not been previously d escribed in the literature and may offer some explanation at the molec ular level concerning the mechanism of impotence and/or decrease in pe nile size after radical prostatectomy.