Our results indicate that mutations in the RLF gene are not a common reason for cryptorchidism and that the common G178A polymorphism has no apparent relationship with this condition.
Although to date no mutations have been found in the human INSL3 gene responsible for cryptorchidism, one causative mutation in the INSL3 receptor (LGR8 or GREAT) has been reported.
The abnormal development of fetal Leydig cells could lead to the reduction of androgen and insulin-like 3, thus causing the male reproductive tract anomalies in male neonates, including cryptorchidism and hypospadias.
Previous studies of undescended testis (UT) has focused on insulin-like hormone 3 (INSL3), the genitofemoral nerve, and androgens in the testicular descent.
A novel V39GINSL3 mutation in a patient with cryptorchidism was identified; however, the functional analysis of the mutant peptide did not reveal compromised function.
While both the insulin-like peptide 3 (INSL3) and its receptor, relaxin family peptide receptor 2 (RXFP2), have been demonstrated to control testicular descent in mice, their link to human cryptorchidism is weak, with no clear cause-effect demonstrated.
This finding agrees with the rare occurrence of INSL3 gene mutations in human cryptorchidism, but needs to be confirmed in a larger series of selected patients.
A second Leydig cell product, insl3, is also significantly down regulated and is likely responsible for the cryptorchidism commonly seen in these phthalate-treated animals.
Under this perspective, we aimed to study the presence of INSL3 allelic variations in a cohort of patients with cryptorchidism and to estimate their potential consequences.
However, although some of mutations were found only in cryptorchid patients, it remains to be verified whether there is a causative link between the presence of mutations in INSL3 or GREAT/LGR8 and the undescended testis phenotype in men.
We performed mutation screening of INSL3 and RXFP2 in human patients with cryptorchidism and control subjects from different populations in Europe and the USA.