The Philosophy of TesticularDescent

Sofikitis N *,


Mammalian male sex determination is an active process involving complex interactions among several genes. SRY and SOX9 are both responsible for testis formation by initializing and maintaining, respectively, Sertoli cell differentiation. Male sexual differentiation is governed by testicular hormones. Testicular descent (TD) and scrotal evolution occur exclusively but not universally in mammals. Although still debatable, this evolutionarily costly process aims at least to secure lower (than core body) testicular temperatures essential for viable sperm production and storage. TD in scrotal mammals is a multistaged process involving interplay of several anatomical structures and hormonal factors. The gubernaculum appears to play a key role, especially in transabdominal TD (TTD). Androgens and Mullerian inhibiting substance have a rather limited, if any, role during TTD. Leydig cell-derived insulin-like 3-hormone acting directly upon the gubernaculum and proteins encoded by homeobox genes represent good candidate controllers of TTD. Inguinoscrotal TD is mediated by androgens probably acting indirectly upon the gubernaculum, in conjunction with mechanical (abdominal pressure) factors. There is a general agreement on the seasonality of testicular maldescent (TMD) at least in the northern hemisphere. Epididymal malformations, impaired testicular histology due to intrinsic testicular defects, mild hypogonadal state, or increased germ cell apoptotic rate mainly due to abnormal testicular temperature may account for the impaired fertility in individuals with TMD. The theory of an intrinsic testicular pathologic process might plausibly explain the association of TMD with the testicular cancer.