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Published on: August 13, 2015
Association of prolactin-induced protein with preputial development of hypospadias
Satoshi Kurokawa1, Yoshiyuki Kojima, Kentaro Mizuno
1Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan.
Insights
This study found lower prolactin-induced protein (Pip) gene expression in hypospadiac rat models, suggesting a role in preputial development and offering a new model for studying hypospadias molecular etiology.
Area of Science:
- Developmental biology
- Genetics
- Molecular biology
Background:
- Hypospadias is a congenital condition affecting male genital development.
- Understanding the molecular basis of hypospadias is crucial for identifying therapeutic targets.
Purpose of the Study:
- To investigate the molecular causes of hypospadias by identifying differentially expressed genes.
- To compare gene expression in hypospadiac and control tissues during critical developmental stages.
Main Methods:
- A rat model of hypospadias was created using flutamide exposure during gestation.
- Gene expression analysis was performed using microarrays, quantitative real-time PCR (qPCR), and Western blot.
- Immunohistochemistry was used to examine protein distribution in rat and human tissues.
Main Results:
- 23 annotated genes, including prolactin-induced protein (Pip), showed significantly lower expression in hypospadiac rat genital tubercles.
- Lower Pip/PIP expression was confirmed by qPCR and Western blot.
- PIP protein was detected in the prepuces of both control and hypospadiac rats and human patients.
Conclusions:
- Reduced Pip/PIP expression in genital tubercles may be linked to preputial development abnormalities in hypospadias.
- The established rat model is valuable for studying the molecular mechanisms of penile, urethral, and preputial development.
- Further research is needed to fully elucidate the molecular etiology of hypospadias.
Objective:
To investigate the molecular aetiology of hypospadias during a critical developmental period by identifying differentially regulated genes in the tissues of individuals with hypospadias and comparing these genes with similar genes in the tissues of control individuals.
Materials And Methods:
Pregnant Sprague-Dawley rats were administered flutamide (7.5 mg) on gestational days 15-17 to produce hypospadiac pups. Dams were killed on gestational day 17, and the genital tubercles (GTs) of male pups were harvested. Gene expression of RNA isolated from the GTs was analysed using an oligonucleotide microarray containing 20,500 genes. The results of microarray analysis were confirmed using quantitative real-time PCR (qPCR). Protein expression levels were studied using Western blot analysis. The distribution of genes associated with GT development in rats was histologically examined. Prepuces harvested from patients with hypospadias and phimosis were immunohistochemically examined for gene distribution.
Results:
Of the 20, 500 genes, 23 annotated genes, including prolactin-induced protein (Pip), in the GTs of the hypospadiac rats were expressed at levels less than half of that of similar genes in the GTs of the control rats. Findings from qPCR and Western blot analysis revealed significantly lower Pip/PIP expression in the GTs of the hypospadiac rats than in those of the control rats. Immunohistochemical analysis revealed PIP expression in the prepuces of the GTs of the control and hypospadiac rats. PIP was expressed in the human prepuces of the patients with hypospadias and phimosis.
Conclusions:
Pip/PIP, expressed at low levels in the GTs of hypospadiac rats, may be associated with preputial development. This model can be useful to elucidate the molecular mechanisms underlying penile and urethral development as well as preputial development. Further studies should provide detailed information regarding the molecular aetiology of hypospadias.
