Exogenous calcitonin gene-related peptide can change the direction of gubernacular migration in the mutant trans-scrotal rat

Abstract

Purpose: The mutant trans-scrotal (TS) rat shows unilateral or bilateral suprainguinal testes in more than 70% of males. Calcitonin gene-related peptide (CGRP) has been proposed as the neurotransmitter released from the genitofemoral nerve (GFN), which controls gubernacular migration to the bottom of the scrotum during inguinoscrotal descent. Results of previous studies in this rat suggest a down-regulation of CGRP receptors in gubernaculum occurring caused by excess release of the neuropeptide from the GFN. The aim of this study was to test the hypothesis that division of the GFN in neonatal TS rats, potentially allowing the gubernaculum to become sensitive to CGRP, followed by exogenous CGRP injections, would change the direction of gubernacular migration and the final position of the testis. Methods: Four study groups were used: group 1 (n = 43), sham operation, in which the peritoneal cavity was opened and the left genitofemoral nerve was exposed but not divided, and oil injections into left hemiscrotum; group 2 (n = 70), division of left GFN and CGRP injections into left hemiscrotum; group 3 (n = 36), sham operation and CGRP injections into left hemiscrotum; group 4 (n = 30), division of left GFN and oil injections into left hemiscrotum. Results: In group 2 (GFN division and CGRP injection), 18 testes were located in a position not previously described in this model. In 16 (23%) rats, the testis was located at the entrance of the internal inguinal ring with the gubernaculum directed down toward the scrotum. This contrasts with the normal position of the testis in the superficial inguinal pouch, where the testis is located superficial to the external oblique muscle, with the gubernaculum directed craniolaterally. In two (3%) rats, there was incomplete descent of the testis. In group 3 (sham operation and CGRP injection), two (6%) testes were located at the internal ring. The remaining testes in the above groups and all of the testes in groups 1 and 4 were found in either the superficial inguinal pouch, completely descended, or adherent to scar tissue. Conclusions: These findings suggest that division of the GFN in neonatal TS rats followed by CGRP injections into the scrotum can change the direction of gubernacular migration in the TS rat. The effectiveness of this experimental model is limited by the inability to accurately localize injected CGRP into the scrotum.