Expression of Mafb is down-regulated in the foreskin of children with hypospadias

Background: Hypospadias is the second most common congenital malformation in males. Although the aetiology of hypospadias is not clear, it is generally thought to be affected by both genetic and environmental endocrine-disrupting factors that affect the development of the urethra, leading to deformity.

Objective: To investigate the difference in expression of the transcription factor Mafb in hypospadias and normal penile tissues and to assess whether it is related to the occurrence of hypospadias.

Study design: Penile tissue was obtained from children with hypospadias who underwent surgical repair at the Children's Hospital of Chongqing Medical University. Patients diagnosed with undescended testicles, intersex status or endocrine abnormalities were excluded from the study. Twenty-five cases with hypospadias (average 3.5 years old) and 15 cases with circumcisions (as control) (average 5 years old) were included in this study. Real-time quantitative polymerase chain reaction, Immunochemistry and Western blot were used to detect the expression of Mafb.

Results: Mafb mRNA expressions in the prepuce of cases with hypospadias was significantly reduced compared with that in the controls [(1.179 ± 0.1275), (0.6652 ± 0.07506), p < 0.05)]. Hypospadias cases also showed decreased Mafb protein expression in the preputial subcutaneous mesenchymal cell layer. Mafb protein levels were significantly decreased in those with hypospadias compared with controls [(1.932 ± 0.1139), (1.006 ± 0.03312), p < 0.05]. However, no such differences were found in Mafb expression between subjects with mild and severe hypospadias.

Discussion: Compared to the normal foreskin, expression of the Mafb gene was down-regulated at both mRNA and protein levels, which was consistent with our RNA-seq sequencing results in Diethylhexyl phthalate (DEHP)-induced hypospadias rats. This study is the first to report abnormal expression of Mafb in the preputial tissue of hypospadias cases. An in-depth study of the relationship between Mafb and cell proliferation, Apoptosis, and urethra development may reveal the pathogenesis of hypospadias.

Conclusion: Expression of the Mafb gene and protein in the foreskin of children with hypospadias is lower than that in normal foreskin. We postulate that such abnormal expression of the Mafb gene may be related to the occurrence of hypospadias and that this abnormal expression may affect the development of the urethra during the embryonic period.