Androgen Receptor mRNA Measured by Quantitative Real Time PCR is Decreased in the Urethral Mucosa of Patients with Middle Idiopathic Hypospadias

Silva, T. S.; Richeti, F.; Cunha, Daniela Patricia Palmeira Santos; Amarante, Antônio Carlos Moreira; Leão, Jovelino Quintino de Souza; Longui, Carlos Alberto

doi:10.1055/s-0033-1333717

Cited by 10 publications

(8 citation statements)

References 5 publications

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“…Later clinical studies support this. The results of these studies demonstrated that AR expression had decreased in both foreskin and urethral mucosa samples taken from patients with hypospadias [Goyal et al, 2007;Silva et al, 2013]. But, Pichler et al [2013] detected increased AR mRNA levels in prepuce samples from patients with hypospadias and evaluated compensatory upregulation at the receptor, decreased AR DNA binding capacity, and AR signal defects.…”

Section: Discussionmentioning

confidence: 99%

A Genetics Study in the Foreskin of Boys with Hypospadias

İnanç¹,

Avlan²,

Eker³

et al. 2023

Mol Syndromol

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Introduction: Hypospadias is a malformation of the genitourinary system in males, characterized by the placement of the urethral opening in the ventral surface of the penis. Although controversies continue about etiology, endocrine disrupting chemicals that disrupt normal endocrine signaling at the receptor or signal transduction level are thought to play an essential role in etiology. This study aimed to investigate the receptor gene expressions of the sex hormones and FGFR2, HOXA13, and TGFB1, which are considered to play an essential role in developing hypospadias. Methods: The samples from the foreskin of 26 patients with hypospadias and 26 healthy children who underwent circumcision operations were collected. ESR1, AR, FGFR2, HOXA13, and TGFB gene expressions were investigated by real-time PCR in samples obtained during surgery. Results: In the hypospadias group, ESR1 expression was increased (p = 0.013), and AR and FGFR2 expressions were decreased, which were found to be statistically significant (p = 0.027 and p = 0.003, respectively). There was no statistically significant difference between hypospadias and control groups in TGFBand HOXA13expression levels (p > 0.05). Discussion: The results suggest that sex hormone receptors and FGFR2 may play an essential role in developing male external genital structures at the gene level. The defects in the expression of these genes can contribute to understanding the development of hypospadias.

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Section: Discussionmentioning

confidence: 99%

A Genetics Study in the Foreskin of Boys with Hypospadias

İnanç¹,

Avlan²,

Eker³

et al. 2023

Mol Syndromol

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“…The human AR gene, also known as the dihydrotestosterone receptor, is located on X-chromosome and a member of the nuclear hormone receptor family. Although AR defect may play a causative role during the development of hypospadias, the AR expression (Balaji et al, 2020;Celayir et al, 2019;Lin et al, 2016;Pichler et al, 2013;Silva et al, 2013;Tack et al, 2019) in hypospadias is still debatable. Lin et al (2016) and Silva et al (2013) reported the decreased AR expression in boys with hypospadias compared with controls.…”

Section: Discussionmentioning

confidence: 99%

Dysregulated expression of androgen metabolism genes and genetic analysis in hypospadias

Chen

Lin

Wang

et al. 2020

Molec Gen & Gen Med

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Background The aberrant expression of genes involved in androgen metabolism and genetic contribution are unclear in hypospadias. Methods We compared gene expression profiles by RNA sequencing from five non‐hypospadiac foreskins, five mild hypospadiac foreskins, and five severe hypospadiac foreskins. In addition, to identify rare coding variants with large effects on hypospadias risk, we carried out whole exome sequencing in three patients in a hypospadias family. Results The average expression of androgen receptor ( AR ) and CYP19A1 were significantly decreased in severe hypospadias ( p < .01) and mild hypospadias ( p < .05), whereas expression of several other androgen metabolism enzymes, including CYP3A4 , HSD17B14 , HSD3B7 , HSD17B7 , CYP11A1 were exclusively significantly expressed in severe hypospadias ( p < .05). Compound rare damaging mutants of AR gene with HSD3B1 and SLC25A5 genes were identified in the different severe hypospadias. Conclusions In conclusion, our findings demonstrated that dysregulation of AR and CYP19A1 could play a crucial role in the development of hypospadias. Inconsistent AR expression may be caused by the feedback loop of ESR1 signaling or combined genetic effects with other risk genes. This findings complement the possible role of AR triggered mechanism in the development of hypospadias.

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“…SNPs identified associated with increased risk [33,36,37]. No significant haplotype association [23].…”

Section: Esr2mentioning

confidence: 97%

New frontiers on the molecular underpinnings of hypospadias according to severity

Piñeyro-Ruiz

Serrano

Perez-Brayfield

et al. 2020

Arab Journal of Urology

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Hypospadias, which is characterised by the displacement of the urethral meatus from its typical anatomical location in males, shows various degrees of severity. In this systematic review, we surveyed our current understanding of the genetics of isolated hypospadias in humans according to the severity of the condition. We found that sequencing and genotyping approaches were the preferred methods of study and that single nucleotide polymorphisms were the most common finding associated with hypospadias. Most genes fell into four genepathway categories related to androgens, oestrogens, growth factors, or transcription factors. Few hypospadias studies classify their findings by severity. Taken together, we argue that it is advantageous to take into consideration the severity of the condition in search of novel candidates in the aetiology of hypospadias.

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Androgen Receptor mRNA Measured by Quantitative Real Time PCR is Decreased in the Urethral Mucosa of Patients with Middle Idiopathic Hypospadias

Cited by 10 publications

References 5 publications

A Genetics Study in the Foreskin of Boys with Hypospadias

A Genetics Study in the Foreskin of Boys with Hypospadias

Dysregulated expression of androgen metabolism genes and genetic analysis in hypospadias

New frontiers on the molecular underpinnings of hypospadias according to severity

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