Morphogenetic Targets and Genetics of Undescended Testis

Abstract

Although important advances in testicular physiology have been achieved, the aetiology of human cryptorchidism remains mostly unknown. Next to sex steroidal signaling pathways, morphogenetic genes are specifically involved in the testicular descent via gubernacular development. Mutations in the human genes encoding insulin-like factor 3 (INSL3) and its Leu-rich repeat-containing G protein-coupled receptor 8 (LGR8), homeobox A10 (HOXA10), zinc finger 214 (ZNF214) and 215 (ZNF215) have occasionally been identified but do not seem to be a frequent cause of cryptorchidism. On the other hand, common polymorphisms in these genes have recently been investigated as contributing risk factors for idiopathic isolated (nonsyndromic) cryptorchidism.

Reinke´s Crystals in Perivascular and Peritubular Leydig Cells

“…In humans, the final stages of the descent occur at the end of the pregnancy (month [8][9] and are controlled by insulin-like 3 (INSL3), members of the HOX gene family, testosterone and Müllerian inhibitory substance (MIS). [25][26][27][28] It is thought that these hormones induce a shortening of the gubernaculum testis, a ligament that is attached to the lower pole of each testis. The shortening of the gubernaculum enables the descent of the testis into the scrotal sac, and the development of spermatogenesis at the start of puberty.…”

“…The shortening of the gubernaculum enables the descent of the testis into the scrotal sac, and the development of spermatogenesis at the start of puberty. [25][26][27][28] If the testis has not descended in a regular way, an individual is diagnosed with cryptorchidism. Cryptorchidism is the most frequent disturbance during the development of the male reproductive system in newborns, aborted foetuses, among boys in puberty and in adults.…”

A Commentary on Association of variants in genes involved in environmental chemical metabolism and risk of cryptorchidism and hypospadias

“…2,3 Consequently, polymorphisms in several genes, such as AR, ESR1, ESR2 and SRD5A2, have been identified as the disease-associated variants. 2,3 However, polymorphisms in genes involved in EED metabolism have been poorly investigated in patients with CO and HS.In this issue of the Journal, Qin et al 6 report an association between single-nucleotide polymorphisms (SNPs) in genes involved in EED metabolism and the risk of CO and HS. They examined 384 SNPs of 15 genes in 334 Japanese male subjects (95 patients with CO, 98 patients with HS and 141 unaffected controls) and 187 Italian male subjects (58 patients with CO and 129 controls), and identified SNPs in 5 genes that were over-represented in the patient group(s) in comparison with the control group.…”

“…1-3 CO and HS usually occur as multifactorial traits subject to a number of genetic and environmental factors with relatively minor effects, although in rare cases these conditions can occur as monogenic disorders because of mutations in genes such as AR and SRD5A2. 2,3 During the last few decades, the prevalence of undermasculinized male genitalia, including HS and CO, has increased in several countries. 4 Similarly, compromised male reproductive function has recently been documented in various wildlife species.…”

“…Till date, several association studies have been performed for patients with CO and HS, in order to identify genetic variants that predispose individuals to these conditions. 2,3 Consequently, polymorphisms in several genes, such as AR, ESR1, ESR2 and SRD5A2, have been identified as the disease-associated variants. 2,3 However, polymorphisms in genes involved in EED metabolism have been poorly investigated in patients with CO and HS.…”