Abstract
BackgroundThe ubiquitin-proteasome system regulate p53, caspase and Bcl-2 family proteins, and is crucial for the degradation of the defective germ cells in testes. Purpose: to evaluate the concentration of ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) in the blood plasma of boys with cryptorchidism and if there is any correlation with patient age.MethodsPatients—50 boys aged 1–4 years (median = 2,4y.) with unilateral cryptorchidism. Exclusion criteria were: previous human chorionic gonadotropin treatment, an abnormal karyotype, endocrine or immunological disorders or any long-term medication. The control group—50 healthy, age matched boys (aged 1–4 years, median = 2,1y.), admitted to the Pediatric Surgery Department for planned herniotomy. To investigate UCHL1 in blood plasma of boys with cryptorchidism, we used a novel technique Surface PLASMON RESONANCE Imaging (SPRI).ResultsThe median concentration of UCHL1 in the blood plasma of boys with cryptorchidism, was 5-folds higher than in boys with inguinal hernia, whose testicles were located in the scrotum. We also noticed statistically significant difference between UCHL1 levels in boys with cryptorchidism up to 2 years old, and above 2 years old. Older boys, whose testicles since birth were located in the inguinal pouch or in the abdominal cavity, had higher concentration of UCHL1 in their blood plasma, than boys from younger group. In the group of cryptorchid boys, we also found slightly lower concentrations of INSL3, without statistical significance and no correlation with UCHL1 levels.ConclusionsUchl1 concentrations in the blood plasma of boys with cryptorchidism, may reflect the heat-induced apoptosis of germ cells. Higher UCHL1 concentrations in older boys with undescended testicles, probably express intensity of germ cell apoptosis, more extensive when testicles are subjected to heat-stress for longer period. Further analyses of UCHL1 may help to elucidate its role in mechanisms influencing spermatogenesis.
Highlights
Testicles which did not descend to the scrotum, are at risk of disturbed spermatogenesis and testicular cancer, caused by elevated temperature in the abdominal cavity or in the inguinal pouch
The median concentration of ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) in the blood plasma of boys with cryptorchidism, was 5-folds higher than in boys with inguinal hernia, whose testicles were located in the scrotum
In the group of cryptorchid boys, we found slightly lower concentrations of INSL3, without statistical significance and no correlation with UCHL1 levels
Summary
Testicles which did not descend to the scrotum, are at risk of disturbed spermatogenesis and testicular cancer, caused by elevated temperature in the abdominal cavity or in the inguinal pouch. Early surgical orchidopexy does not change the risk of malignant transformation [2]. Ubiquitin-proteasome system is crucial to the regulation of this process. DUBs are divided into ubiquitin C-terminal hydrolases (UCHs) and ubiquitin specific proteases (UBPs) [5]. Kwon et al suggested that one of those enzymes—ubiquitin Carboxyl-terminal hydrolase 1 (UCHL1) “plays a role in balancing the expression of apoptosis-inducing and apoptosis-protecting proteins”[6]. UCHL1 is expressed in gonocytes, already at 14 days of gestation [8]. The ubiquitin-proteasome system regulate p53, caspase and Bcl-2 family proteins, and is crucial for the degradation of the defective germ cells in testes. Purpose: to evaluate the concentration of ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) in the blood plasma of boys with cryptorchidism and if there is any correlation with patient age
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