Regulation of testicular descent

Abstract

Testicular descent occurs in two morphologically distinct phases, each under different hormonal control from the testis itself. The first phase occurs between 8 and 15 weeks when insulin-like hormone 3 (Insl3) from the Leydig cells stimulates the gubernaculum to swell, thereby anchoring the testis near the future inguinal canal as the foetus grows. Testosterone causes regression of the cranial suspensory ligament to augment the transabdominal phase. The second, or inguinoscrotal phase, occurs between 25 and 35 weeks, when the gubernaculum bulges out of the external ring and migrates to the scrotum, all under control of testosterone. However, androgen acts mostly indirectly via the genitofemoral nerve (GFN), which produces calcitonin gene-related peptide (CGRP) to control the direction of migration. In animal models the androgen receptors are in the inguinoscrotal fat pad, which probably produces a neurotrophin to masculinise the GFN sensory fibres that regulate gubernacular migration. There is little direct evidence that this same process occurs in humans, but CGRP can regulate closure of the processus vaginalis in inguinal hernia, confirming that the GFN probably mediates human testicular descent by a similar mechanism as seen in rodent models. Despite increased understanding about normal testicular descent, the common causes of cryptorchidism remain elusive.

37,X/38,XY Mosaicism in a Cryptorchid Bengal Cat with Müllerian Duct Remnants

“…Insufficient secretion of hormones by the hypoplastic testes may explain the cryptorchid inguinal and prescrotal location. Because transabdominal migration was complete, failure in fetal Leydig cells' production of insulin-like 3 peptide, which appears to be the main regulator in this descensus phase, is less likely compared to testicular androgens, which have indirect and direct roles in the transabdominal and inguinoscrotal phases [Hughes and Acerini, 2008;Meyers-Wallen, 2009;Hutson et al, 2015].…”

Characterizing the reproductive transcriptomic correlates of acute dehydration in males in the desert-adapted rodent,Peromyscus eremicus

“…in humans: [110]; in bulls: [111]). Insl3 is also critical for the first phase of testicular descent, the transabdominal phase, which occurs during fetal development in rodents; but Insl3 does not appear to be involved in the inguinoscrotal phase which happens in sexually immature or inactive male rodents (reviewed in [112]). Lower Insl3 expression in the testes of acutely dehydrated mice leads us to suggest that fertility may be attenuated due to acute water deprivation.…”

Why do undescended testes and posterior urethral valve occur together?

“…In the transabdominal phase, androgens cause regression of the cranial suspensory ligament and insulinlike hormone 3 (INSL3) causes enlargement of the gubernaculum to hold the testicles near the inguinal canal as the foetal abdominal cavity enlarges at 8-15 weeks. In the inguinoscrotal phase at 25-35 weeks androgens mediate migration of the gubernaculum to the scrotum [8]. UDT represents a failure of this process in some form, and dramatically increases the risk of infertility and testicular cancer.…”

“…We aimed to review the literature to identify publications documenting co-occurrence of UDT and PUV, and to summarise the theories of co-occurrence. Methods A search of the literature (Embase, Medline, Pubmed; 1947-2015 was undertaken to identify publications describing the link between UDT in PUV patients, as well as PUV in UDT patients. Ten publications in English were found with both UDT and PUV: 9 articles describing the frequency of UDT in patients with PUV, and 1 article examining the frequency of PUV in infants with UDT.…”