Literature on the aetiology of hypospadias in the last 5 years: molecular mechanism and environmental factors

Yang, Qingran; Qu, Wei; Yang, Li; Wang, K.; Tu, Hausamen; Wang, J.

doi:10.1111/and.12125

Cited by 10 publications

(8 citation statements)

References 51 publications

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“…However, the exact etiology and molecular mechanisms involved in its development are still unclear. 11 Ongoing research sheds light on the genetic, environmental, endocrine, and other factors involved in this defect. 12 Defects in the adrenal gland steroid synthesis pathway can lead to the development of HS.…”

Section: Discussionmentioning

confidence: 99%

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

Bangalore,

Asthana,

et al. 2024

J Pediatr Genet

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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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Section: Discussionmentioning

confidence: 99%

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

Bangalore,

Asthana,

et al. 2024

J Pediatr Genet

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“…14,15 Environmental factors are variable as chemical substances, antiandrogen drugs, dietary habits of pregnant mothers, and the medications used in in vitro fertilization and epilepsy treatment. 10,11,[15][16][17][18] Placental insufficiency is one of the reasons that has been mentioned lately. 2 It has been claimed that early placental insufficiency leads to low human chorionic gonadotropin (hCG) secretion, which leads to decreased fetal testosterone production, potentially causing hypospadias at the end of this process.…”

Section: Discussionmentioning

confidence: 99%

Hypospadias and the Use of the Ages and Stages Questionnaire to Evaluate Neurodevelopmental Status of Boys with Hypospadias

et al. 2021

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Introduction Placental insufficiency is one of the reasons for the reduction of hormone production. Thus, if one of the suspected causes of hypospadias is placental insufficiency, then the neurodevelopmental status of boys with hypospadias may be impaired. The aim of this study was to evaluate the neurodevelopmental status of boys with hypospadias and guide the parents of those who need support to related departments for early intervention. Materials and Methods Boys were divided into two groups, those with hypospadias (group H) and healthy children undergoing traditional circumcision (group C). The parents of the boys completed the Ages and Stages Questionnaire (ASQ) and ASQ–Social Emotional (SE), both of which are screening instruments for the early identification of developmental and social–emotional problems, respectively. Results Seventy-eight boys had hypospadias and 59 were admitted for traditional circumcision. The group H had statistically significant more impaired scores than group C in communication, gross motor, and personal–social skill sections. The multivariate logistic regression analysis revealed that hypospadias was the independent predictive factor for communication and personal–social skills. Conclusion Hypospadias and neurologic impairment may share common etiologic factors. Accordingly, physicians should keep in mind that if a boy presents with hypospadias, the possibility of having neurologic impairment is higher than normal population and early intervention has crucial importance. Every boy with hypospadias should be evaluated for neurodevelopmental status.

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“…Initially, our findings showed that the proportions of patients with congenital hypospadias in premature, low birth weight infants and gestational abnormality were significantly higher than those in the control group. To our knowledge, genetic factors have been reported to be highly involved in the etiology of hypospadias in some studies, including gene mutation that contributes to hypospadias in the presence of some genes being important for the development of the urogenital system [ 18 ]. Interestingly, a variety of environmental factors and risk of hypospadias were explored according to Zanden et al; pregnancy complications, maternal drug use, low birth weight, and other environmental factors were regarded as key reasons for increasing the risk of hypospadias [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Polymorphism in the RYR1 C6487T Is Associated with Severity of Hypospadias in Chinese Han Children

Zhang

Jia

et al. 2018

BioMed Research International

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Objective Hypospadias is a common congenital malformation of the male external genitalia. Most cases have an unknown etiology, which is probably a mix of monogenic and multifactorial forms, implicating both genetic and environmental factors. Ryanodine receptor 1 (RYR1) mutations are a common cause of congenital diseases associated with both dominant and recessive inheritance in humans. Herein, we evaluated the correlations of RYR1 C6487T polymorphism with the risk and severity of hypospadias. Methods 263 congenital hypospadias children and 312 healthy children were recruited. The polymorphism of RYR1 C6487T in the peripheral blood was detected by polymerase chain reaction-restriction fragment length polymorphism, and different genotypes and allelic genes were analyzed to explore their associations with the risk of congenital hypospadias. Results The distribution frequencies of CC/CT/TT genotypes and two alleles (C and T) at RYR1 C6487T showed significant differences between the case and control groups (P < 0.05). The frequency of C allele in the case and control groups was 46.95% and 54.94%, respectively, and of T allele was 53.05% and 45.06% (P < 0.05). In addition, the distribution frequency of CC/CT/TT genotypes exhibited significant difference between patients with mild hypospadias and those with moderate or severe hypospadias (all P > 0.05), suggesting that RYR1 C6487T polymorphism is correlated with the severity of congenital hypospadias (X2 = 13.722, P = 0.001). Conclusion Our study demonstrated that RYR1 C6487T polymorphism might be associated with an increased risk of congenital hypospadias in Chinese Han children. Our findings highlight the heterogeneous nature of hypospadias genetic susceptibility.

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Literature on the aetiology of hypospadias in the last 5 years: molecular mechanism and environmental factors

Cited by 10 publications

References 51 publications

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

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

Hypospadias and the Use of the Ages and Stages Questionnaire to Evaluate Neurodevelopmental Status of Boys with Hypospadias

Genetic Polymorphism in the RYR1 C6487T Is Associated with Severity of Hypospadias in Chinese Han Children

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