Factors controlling testis descent

Abstract

Descent of the testis from an intra-abdominal site in foetal life to an extracorporeal location after birth is a mandatory developmental process to ensure that the mature testis promotes normal spermatogenesis. The two phases of transabdominal and inguinoscrotal descent occur approximately during the first and last thirds of gestation respectively. Key anatomical events to release the testis from its urogenital ridge location and to guide the free gonad into the scrotum are the degeneration of the cranio-suspensory ligament and a thickening of the gubernaculum. Androgens play a role in both these processes, particularly with respect to enabling the testis to traverse the inguinal canal in the final phase of descent. Experiments in animals suggest that androgens mediate this effect via the release of calcitonin gene-related peptide by the genitofemoral nerve, but direct evidence for such a mechanism is lacking in humans. The transabdominal phase of descent is under the control of insulinlike 3 (INSL3), a product of the Leydig cells. Definitive evidence of its role in rodent testis descent is illustrated by the phenotype of bilateral cryptorchidism in Insl3K/K null mice. Circulating levels of INSL3 are higher in boys at puberty, are undetectable in girls and are lower in boys with undescended testes. A minority also have a mutation either in the INSL3 gene or affecting its receptor gene, relaxin/insulin-like family peptide receptor 2 (LGRF8). Other factors that may play a role in testis descent include the anti-Mullerian hormone and members of the HOX gene family. Evidence that the prevalence of undescended testis may be increasing provides a phenotypic readout for the effects of postulated chemicals in the environment interfering in some way with the action of factors that control testis descent. Epidemiological studies point to profound geographical variations in prevalence in countries such as Denmark and Finland. Associations have been found with levels of chemicals labelled as endocrine disruptors being higher in breast milk samples from mothers with cryptorchid boys when compared with controls. The adverse effects of these compounds (e.g. bisphenol A) can be replicated in the offspring of dams exposed during pregnancy. A sensitive marker of an anti-androgen effect of a compound is a reduction in the anogenital distance, an anthropometric measurement that is significantly greater in males compared with females. The observation of an association between the anogenital distance in infant boys and the level of pesticides in the urine of their mothers in late gestation indicates that this has the potential to be a useful surrogate marker of the effects of environmental chemicals on testis descent in human population studies. The rightful place for the testis at birth is in the scrotum in order to provide the temperature differential essential for normal spermatogenesis. Appropriate screening programmes and early surgical intervention are the prerequisites to ensure optimal fertility in adulthood and a con...

Assessment and Management of Inguinal Hernia in Infants

“…2 During the intra-abdominal phase, the testis, which derives from the bipotential gonad originating at the urogenital ridge, is attached to the diaphragm by the craniosuspensory ligament. In the male fetus, regression of the craniosuspensory ligament results in transabdominal migration of the testis between 8 and 15 weeks postconception.…”

Development of the Gubernaculum During Testicular Descent in the Rat

“…It is generally agreed that testicular descent in mammals occurs in two distinct steps with different anatomy and hormonal regulation (Hutson, 1985;Amann and Veeramachaneni, 2007;Foresta et al, 2008;Hughes and Acerini, 2008;Feng et al, 2009). In the first, or transabdominal phase, the genitoinguinal ligament, also known as the ''gubernaculum,'' undergoes enlargement or the ''swelling reaction.''…”

Regulation of the reproductive cycle and early pregnancy by relaxin family peptides

“…INSL3 is made by the fetal-type Leydig cells (FLC) of the embryonic testis very shortly after SRYdependent sex determination. In humans, this INSL3 can be detected in amniotic fluid already at 12 weeks of gestation (AnandIvell et al, 2008), and the timing of INSL3 production in the fetus coincides with the first transabdominal phase of testicular descent Hughes and Acerini, 2008). In fact the failure of the testes to descend (cryptorchidism) is the sentinel phenotype of INSL3-as well as RXFP2-knockout mice (Nef and Parada, 1999;Zimmermann et al, 1999;Kamat et al, 2004).…”