Role Of INSL-3 Gene Mutations In Cryptorchidism

Background Cryptorchidism is a failure of one or both testes 'descend' into the scrotum through the inguinal canal along the peritoneum process vaginalis according to the normal growth process at the embryonic time,staying at different spots of drop process.It is the most frequent congenital birth defect of the urogenital tract,while the morbility and risk are high.And the consequences including increased risk to develop azoospermatism and testicular tumors,and at meanwhile there is a risk influence another normal testicle,leads to masculine sterility.The complex, multistage testicular descent requires the interaction of anatomical and hormonal factors and consists of two major phases.Normal testicular descent is a result of the interaction of the neuroendocrine factor by the gene regulation and anatomical factor. The abnormality of gene regulation,insufficiency of neuroendocrine function and the abnormality of anatomy constitute a etiological chain of the cryptorchidism,and the abnormality of anatomy become a final factor or outcome.However the etiology of cryptorchidism remains unknown,reflecting our faint knowledge of the mechanisms regulating testicular descent from abdomen to scrotum during embryonic development.And most research support that it's the result of the genetic factor and the environmental factor.Insl3^-/- male mice exhibit bilateral cryptorchidism due to impaired development of the gubernaculum.The relationship between cryptorchidism and the mutation of INSL-3 become a warm spot of reseaches.Objective To study the relationship between cryptorchidism and the mutation of INSL-3 in Northern China,especially in JingJirdi area,China,and the aim is to explore the pathogenesy from molecular biology.Methods To select 60 children with cryptorchidism and 60 healthy ones trabantly. Genomic DNA was extracted from the white blood cells of blood samples.The DNA fragments of 2 exons of INSL-3 were acquired by polymerase chain reaction(PCR) amplification.Direct DNA sequencing was carried out after purification.Then we scaned the mutation and analysed the relevant mechanism.Result 1.All the PCR products were directly sequenced in both sense and antisense orientations.There are two kinds of nucleotide changes.The first change,2 of the 60 patients,was G→T at nucleotide position 276 and lead to codon 92 from Glutamine to Histidine.The second change was 477C/G which not in the coding sequence.It did not change the amino acid.2.Mutation rate is 5.0%(3/60).3.There is none mutation of INSL3 in the control.4.After scaning in NCBI,we haven't found the same mutation site reported.Conclusion 1.Q92H was first time reported.2.QPLPQ of INSL-3 may be the correlated sequence caused the cryptorchidism.3.477C/G,did not change the amino acid,may be a genetic symbol.4.The frequency of the INSL-3 mutation as a cause of the cryptorchidism is low.5.It is necessary to further identify the genetic mutation, proteinic function and the etiology,development and complication of cryptorchidism.