Quantitative measurement of the androgen receptor in prepuces of boys with and without hypospadias
Year: 2013
Type: editorial
Abstract: Although hypospadias is one of the most common congenital anomalies, its aetiology remains unknown. It is thought that hypospadias is caused by genetic susceptibility in combination with adverse environmental exposure, which disrupts the normal balance of androgens and oestrogens required for normal sexual differentiation of the external genitalia (Fig. 1). Normal genes and a normal hormonal environment result in normal external genitalia development. Abnormal genes and/or genetic susceptibility/epigenetic changes result in hypospadias 1. Likewise, endocrine disruptors may affect the normal hormonal balance of androgen and oestrogen and/or influence epigenetic changes, resulting in hypospadias 2. Aetiology of hypospadias. Several reports have shown an increase in the incidence of hypospadias over the last 30 years 3. Clearly, genes and the environment are involved since we know that there is a greater incidence among siblings of children with hypospadias. Epidemiological studies have also shown that diet is associated with a greater incidence of hypospadias; specifically, exposure to phytoestrogens from soya products during pregnancy is associated with an increased risk 4. In addition, recent evidence suggests that epigenetic factors may also play a role in causing hypospadias 5. This new epigenetic hypothesis fits in with the excellent present study by Pichler et al. Their quantitative measurement of differences in the androgen receptor in the discarded foreskin collected at the time of surgical repair in boys with hypospadias compared with those of a cohort undergoing circumcision is further evidence of the critical nature of the androgen pathway in normal and abnormal development. Their work complements work previously performed in our laboratory, showing that the androgen receptor is overexpressed in boys with severe hypospadias 6. The mechanism of this overexpression may be via the genetic pathway ZEB1. The definitive mechanism for this process and the other genes involved remain to be elucidated. Are epigenetic factors involved and/or is this abnormality a result of environmental exposure? Although these questions remain unanswered, without this type of basic scientific work, it will be difficult to make progress towards our ultimate goal: in this case, a better understanding of hypospadias, which will ultimately lead to a reliable preventative strategy to reduce the incidence of hypospadias in the future. None declared.
Source: British Journal of Urology
Author: Laurence Baskin
Language: English
Subfield: Urology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2136262357