Development of the gubernaculum during testicular descent in the rat.

Gubernacular elongation during inguinoscrotal testicular descent and cremaster muscle development remains poorly described in mammals. The role of the genitofemoral nerve (GFN) remains elusive. We performed detailed histological analysis of testicular descent in normal rats to provide a comprehensive anatomical description for molecular studies. Fetuses and neonatal male offspring (5-10 per group) from time-mated Sprague-Dawley dams (embryonic days 15, 16, and 19; postnatal days 0, 2, and 8) were prepared for histology. Immunohistochemistry was performed for nerves (Class III tubulin, Tuj1) and muscle (desmin). At embryonic days 15 and 16, the gubernaculum and breast bud are adjacent and both supplied by the GFN. By embryonic day 19, the breast bud has regressed and the gubernacular swelling reaction is completed. Postnatally, the gubernacular core regresses, except for a cranial proliferative zone. The cremaster is continuous with internal oblique and transversus abdominis. By postnatal day 2 (P2), the gubernaculum has everted, locating the proliferative zone caudally and the residual mesenchymal core externally. Eversion creates the processus vaginalis, with the everted gubernaculum loose in subcutaneous tissue but still remote from the scrotum. By P8, the gubernaculum has nearly reached the scrotum with fibrous connections attaching the gubernaculum to the scrotal skin. A direct link between GFN, gubernaculum, and breast bud suggests that the latter may be involved in gubernacular development. Second, the cremaster muscle is continuous with abdominal wall muscles, but most of its growth occurs in the distal gubernacular tip. Finally, gubernacular eversion at birth brings the cranial proliferative zone to the external distal tip, enabling gubernacular elongation similar to a limb bud.

The role of the gubernaculum in the descent and undescent of the testis.

Testicular descent to the scrotum involves complex anatomical rearrangements and hormonal regulation. The gubernaculum remains the key structure, undergoing the 'swelling reaction' in the transabdominal phase, and actively migrating out of the abdominal wall to the scrotum in the inguinoscrotal phase. Insulin-like hormone 3 (Insl3) is the primary regulator of the first phase, possibly augmented by Müllerian inhibiting substance/anitmüllerian hormone (MIS/AMH), and regression of the cranial suspensory ligament by testosterone. The inguinoscrotal phase is controlled by androgens acting both directly on the gubernaculum and indirectly via the genitofemoral nerve, and release of calcitonin gene-related peptide from its sensory fibres. Outgrowth of the gubernaculum and elongation to the scrotum has many similarities to an embryonic limb bud.Cryptorchidism occurs because of both failure of migration congenitally, and failure of elongation of the spermatic cord postnatally. Germ cell development postnatally is disturbed in congenital cryptorchidism, but our current understanding of germ cell biology suggests that early orchidopexy, around 6 months of age, should provide a significant improvement in prognosis compared with a previous generation. Hormone treatment is not currently recommended. Acquired cryptorchid testes may need orchidopexy once they no longer reach the scrotum, although this remains controversial.