Exogenous calcitonin gene-related peptide perturbs the direction and length of gubernaculum in capsaicin-treated rats

Abstract

Calcitonin gene-related peptide (CGRP) released from the genitofemoral nerve (GFN) is proposed to control gubernacular migration to the scrotum during inguinoscrotal descent. As previous studies suggested that both CGRP and androgens are necessary to stimulate gubernacular elongation and proliferation, this study aimed to test whether CGRP perturbed growth of the gubernaculum by exogenous injection in a rat model of GFN blockade with an intact androgen pathway. Sprague-Dawley rats (day 0, n = 34) were injected with capsaicin (sensory neurotixin) or vehicle. CGRP (25 microl of 2 x 10 5 molar concentration) Or castor oil was administered at the umbilicus 24 h later, then every other day thereafter for 10 days. Groups of rats were sacrified on days 8 and 28, and the tip of the gubernaculunx was identified in relation to the scrotum and umbilicus. The length of the processus vaginalis (PV) was measured. In group 1 (capsaicin and CGRP), at 8 days of age (n = 8) the testes were found in the intraabdominal or suprainguinal position in 87.5% (14 testes) and the tip of the gubernaculum was oriented more laterally than normal. However the mean PV length was 5.1 mm, which was shorter than control groups (9-10.8 mm) (P < 0.001, t-test). On the other hand, at day 28, the testes were located proximal to the internal inguinal ring in 66.7% (8 testes) with their gubernacular tip oriented in part towards the umbilicus. The mean of the PV length was 12.2 mm, which was significantly decreased compared to other groups (P < 0.001, t-test). In group 2 (capsaicin and castor oil) and group 3 (vehicle and CGRP) the testes of one rat in each group at 28 days of age were located in the abdomen at the internal inguinal ring with the distal gubernacular attachment lying free and directed caudally towards the scrotum, while the rest of the testes were found in the normal location. These findings suggest that chemical interruption of sensory nerves followed by CGRP injections in rats can perturb gubernacular growth and can change the direction of migration.