Novel combined insulin-like 3 variations of a single nucleotide in cryptorchidism

Abstract

Background Insulin-like 3 hormone (INSL3) is involved in the process of testicular descent, and has been thoroughly studied in cryptorchidism. However, INSL3 allelic variations found in the human genome were heterozygous and only a few of them were found exclusively in patients with cryptorchidism. 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. Methods Blood samples were collected from 46 male patients with non-syndromic cryptorchidism and from 43 age-matched controls. DNA extraction and polymerase chain reaction (PCR) were performed for exons 1 and 2 of the INSL3 gene in all subjects. Sequencing analysis was carried out on the PCR products. All data were grouped according to testicular location. Results Seven variations of a single nucleotide (SNVs) were identified both in patients with cryptorchidism and in controls: rs2286663 (c.27G > A), rs1047233 (c.126A > G) and rs6523 (c.178A > G) at exon 1, rs74531687 (c.191-30C > T) at the intron, rs121912556 (c.305G > A) at exon 2 and rs17750642 (c.*101C > A) and rs1003887 (c.*263G > A) at the untranslated region (UTR). The allelic variants rs74531687 and rs121912556 were found for the first time in the Greek population. The novel homozygotic combination of the three allelic variants rs1047233-rs6523-rs1003887 seemed to present a stronger correlation with more severe forms of cryptorchidism. Conclusions The combination of specific INSL3 SNVs rather than the existence of each one of them alone may offer a new insight into the involvement of allelic variants in phenotypic variability and severity.

Individualized Treatment of Inguinal Hernia in Children

“…The gubernaculum originates in two triangular mesenchymal condensations, the inguinal plica dorsal to the Wolffian duct and the inguinal crista opposite the plica [6,7]. The growth and differentiation of the gubernaculum is induced by insulin-like factor 3 (INSL3), which is secreted by Leydig cells [8,9]. The pelvic portion of the gubernaculum is created by merging the mesonephric and inguinal portions.…”

Correlation between insulin‐like peptide 3 and appendix testis length in congenital cryptorchidism

“…1 Insulin-like peptide-3 (INSL3) is a hormone that is produced in the pre-and post-natal Leydig cells of the testis and plays a major role in testicular descent. [2][3][4][5][6][7] According to studies in rodents, prenatally expressed INSL3 is necessary for testicular descent, 8,9 which involves a transabdominal and an inguinoscrotal phase. 10 It has been shown in animal studies that the absence of INSL3 results in bilateral intra-abdominal cryptorchidism.…”