Understanding the Endocrine and Molecular Signaling Cascade Regulation Pathways in Children with Hypospadias.

IF 0.4 Q4 PEDIATRICS Journal of pediatric genetics Pub Date : 2024-06-24 eCollection Date: 2024-12-01 DOI:10.1055/s-0044-1787670
Raghunath V Bangalore, Suramya Asthana, Reshma V R, Deepak Kumar Saini, Anand Alladi
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Abstract

Hypospadias (HS) is a congenital defect that occurs due to defective androgenization. It is characterized by the aberrant location of the urinary meatus on the ventral aspect of the penis with various degrees of severity. The molecular mechanisms and genetic associations underlying the condition remain largely unknown. Existing literature revolves around surgical and medical management of the condition. Human chorionic gonadotropin pretreatment in HS is proposed to decrease the severity of the anomaly and improve the clinical outcome of surgery. The underlying mechanisms that drive these outcomes have not been explored. Few studies have explored the endocrine signaling and pathways which lead to the development of the condition. Hence, a prospective study was conducted to understand the same. Eighteen children with mid or proximal penile HS were included as cases, and nine children undergoing circumcision for phimosis (nonpathological) were included as controls. Serum samples from all these children and preputial skin samples taken during surgery were used in the analysis. The hormonal milieu was normal in all children in our cohort. A comparison of previously reported genes with our cohort sequencing revealed changes in several major pathways involved in cell proliferation and differentiation, cell signaling, angiogenesis, and immune response pathways. Compared with healthy controls, HS subjects had 152 differentially expressed genes. Of these, 93 genes were up-regulated, and 59 genes were found to be significantly down-regulated. The gene expression evaluation also showed changes in expression patterns in inflammatory genes and link RNAs, unlike previously reported genes.

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了解尿道下裂儿童的内分泌和分子信号级联调节途径。
尿道下裂(HS)是一种先天性缺陷,是由于雄性激素分泌缺陷造成的。其特征是尿道口异常地位于阴茎腹侧,严重程度不一。该病症的分子机制和遗传关联在很大程度上仍然未知。现有文献主要围绕该病症的手术和药物治疗展开。人类绒毛膜促性腺激素对HS的预处理被认为可降低异常的严重程度并改善手术的临床效果。目前尚未探究产生这些结果的内在机制。很少有研究探讨了导致该病症发生的内分泌信号传导和途径。因此,我们开展了一项前瞻性研究来了解这一问题。18名患有阴茎中段或近端HS的儿童被列为病例,9名因包皮过长(非病理性)而接受包皮环切术的儿童被列为对照。分析中使用了所有这些儿童的血清样本和手术时采集的阴茎前皮肤样本。我们队列中所有儿童的激素环境均正常。将以前报告的基因与我们的队列测序结果进行比较后发现,涉及细胞增殖和分化、细胞信号传导、血管生成和免疫反应途径的几个主要通路发生了变化。与健康对照组相比,HS受试者有152个表达不同的基因。其中,93个基因上调,59个基因显著下调。基因表达评估还显示炎症基因和链接 RNA 的表达模式发生了变化,这与之前报道的基因不同。
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期刊介绍: The Journal of Pediatric Genetics is an English multidisciplinary peer-reviewed international journal publishing articles on all aspects of genetics in childhood and of the genetics of experimental models. These topics include clinical genetics, molecular genetics, biochemical genetics, medical genetics, dysmorphology, teratology, genetic counselling, genetic engineering, formal genetics, neuropsychiatric genetics, behavioral genetics, community genetics, cytogenetics, hereditary or syndromic cancer genetics, genetic mapping, reproductive genetics, fetal pathology and prenatal diagnosis, multiple congenital anomaly syndromes, and molecular embryology of birth defects. Journal of Pediatric Genetics provides an in-depth update on new subjects and current comprehensive coverage of the latest techniques used in the diagnosis of childhood genetics. Journal of Pediatric Genetics encourages submissions from all authors throughout the world. The following articles will be considered for publication: editorials, original and review articles, short report, rapid communications, case reports, letters to the editor, and book reviews. The aim of the journal is to share and disseminate knowledge between all disciplines in the field of pediatric genetics. This journal is a publication of the World Pediatric Society: http://www.worldpediatricsociety.org/ The Journal of Pediatric Genetics is available in print and online. Articles published ahead of print are available via the eFirst service on the Thieme E-Journals platform.
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