INVESTIGATIVE UROLOGY

Experimental varicocele induces testicular germ cell apoptosis in the rat
Barqawi A, Caruso A, Meacham RB
From the Division of Urology, Department of Surgery, University of Colorado School of Medicine, Denver, Colorado, USA
J Urol. 2004; 171: 501-3

• Purpose: We evaluated the impact of experimentally created varicocele on ipsilateral and contralateral testicular germ cells in the rat.
• Materials and Methods: Experimental left varicocele was created by partial ligation of the left renal vein in 17 adult male Sprague-Dawley rats. An additional 5 rats that underwent laparotomy and renal vein handling without ligation served as sham surgical controls. Five rats that underwent no surgical or other intervention served as a control group. Rats were sacrificed 7 (5), 14 (5) or 28 (7) days following varicocele creation. Germ cell apoptosis was quantified using a TUNEL assay. The results of this assay are expressed as the number of apoptotic germ cell nuclei per seminiferous tubular cross section. The presence of apoptosis was confirmed by cellular ultrastructure evaluation using transmission electron microscopy.
• Results: Control and sham animals were found to have a mean of 0.05 and 0.15 apoptotic germ cells per seminiferous tubular cross section, respectively. Rats sacrificed 7, 14 and 28 days after varicocele creation were found to have 0.15, 0.23 and 0.27 apoptotic germ cells per tubule in the ipsilateral testis, and 0.14, 0.16 and 0.17 apoptotic germ cells per tubule in the contralateral testis, respectively. Compared with control animals a statistically significant increase in the number of apoptotic germ cells per tubular cross section was noted 14 days following varicocele creation in the ipsilateral testis (p < 0.05).
• Conclusions: The creation of experimental varicocele generated an increase in germ cell apoptosis in the ipsilateral testis at 14 days compared with control animals.
  
  
• Editorial Comment
  Until now, a precise relationship between varicocele and infertility is yet to be clarified. The present study analyzed the testicular germ cell apoptosis in the rat as consequence of experimentally induced varicocele.
  The authors used an established animal model for the creation of testicular varicocele for assessing the time impact of such a lesion on germ cell apoptosis. The findings confirmed that the normal Sprague-Dawley rat demonstrates low levels of germ cell apoptosis (0.05 apoptotic germ cells per tubular cross section). Also, the animals subjected to laparotomy without partial ligation of the renal vein demonstrated germ cell apoptosis that was not statistically different from that in normal controls. On the other hand, rats that underwent experimental varicocele creation showed significantly increased levels of germ cell apoptosis in the ipsilateral testis 14 days following varicocele creation.
  Although the animal model of varicocele clearly differs from the clinical varicocele seen in humans, the findings of the present study indicate that experimental varicocele creation in the rat generates a time dependent increase in germ cell apoptosis in the ipsilateral testis. These findings may be the explanation of the mechanism by which varicocele exerts a pathological influence on testicular function in a clinical setting.

Dr. Francisco J.B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil