Hypospadias: Interactions between environment and genetics

Kalfa, Nicolas; Philibert, Pascal; Baskin, Laurence S.; Sultan, Charles

doi:10.1016/j.mce.2011.01.006

Cited by 93 publications

(68 citation statements)

References 128 publications

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“…Similar to homosexuality, both traits are usually not shared among monozygotic twins (approximately 25% concordance for each trait; Fredell et al 2002;Jensen et al 2010). Also like homosexuality being elevated in individuals with loss of function at the CYP21 gene (but this gene not being a major cause of female homosexuality), extensive genetic studies have found that while loss of function at some candidate genes can lead to both hypospadias and cryptorchidism, the majority of cases are not associated with any known mutations (reviewed in Bay et al 2011;Kalfa et al 2011). Further evidence for a substantial nongenetic contribution in the case of cryptorchidism is: higher concordance (twofold) between dizygotic twins than that between singleton brothers (Jensen et al 2010); and the high incidence of cryptorchidism (up to 70%) observed in some isolated wildlife populations despite no genetic evidence for inbreeding or a founder effect-presumably due to an environmental hormone-signaling disruptor (Latch et al 2008).…”

Section: Arbitrary Traitsmentioning

confidence: 99%

Homosexuality as a Consequence of Epigenetically Canalized Sexual Development

Rice

Friberg²,

Gavrilets³

2012

The Quarterly Review of Biology

111

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Section: Arbitrary Traitsmentioning

confidence: 99%

Homosexuality as a Consequence of Epigenetically Canalized Sexual Development

Rice

Friberg²,

Gavrilets³

2012

The Quarterly Review of Biology

111

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“…However, the leading hypothesis is that a combination of genetic susceptibility and environmental exposure to endocrine disruptors might cause this anomaly. 4,5 accordingly, if exposure to environmental agents linked to hypospadias is avoided, then the incidence of hypospadias might be reduced. 6,7 agents that have been implicated in the aetiology of hypospadias based upon epidemiological studies in humans and experimental animal studies include progestins, oestrogens, loratidine and various agents that produce an 'androgen blockade' , including phthalates and anti-androgenic fungicides such as vinclozolin and procymidone.…”

Section: Introductionmentioning

confidence: 99%

Current understanding of hypospadias: relevance of animal models

et al. 2015

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| Hypospadias is a congenital abnormality of the penile urethra with an incidence of approximately 1:200-1:300 male births, which has doubled over the past three decades. The aetiology of the overwhelming majority of hypospadias remains unknown but appears to be a combination of genetic susceptibility and prenatal exposure to endocrine disruptors. Reliable animal models of hypospadias are required for better understanding of the mechanisms of normal penile urethral formation and hence hypospadias. Mice and/ or rats are generally used for experimental modelling of hypospadias, however these do not fully reflect the human condition. To use these models successfully, researchers must understand the similarities and differences between mouse, rat and human penile anatomy as well as the normal morphogenetic mechanisms of penile development in these species. Despite some important differences, numerous features of animal and human hypospadias are shared: the prevalence of distal penile malformations; disruption of the urethral meatus; disruption of urethra-associated erectile bodies; and a common mechanism of impaired epithelial fusion events. Rat and mouse models of hypospadias are crucial to our understanding of hypospadias to ultimately reduce its incidence through better preventive strategies.

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“…Although a large number of studies have been conducted to examine hypospadias, the causes are not fully understood. Genetic, endocrine, and environmental factors are thought to contribute to the etiology of isolated hypospadias (Willingham and Baskin, 2007;Kalfa et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Androgen receptor gene CAG repeat polymorphism and risk of isolated hypospadias: results from a meta-analysis

et al. 2015

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ABSTRACT. Studies investigating the association between the CAG repeat polymorphism and the risk of isolated hypospadias have reported conflicting results. The aim of this study was to quantitatively summarize the evidence for such a relationship. Two investigators independently searched the Medline, Embase, CNKI, and Wanfang databases. Weighted mean difference and 95% confidence intervals for the CAG repeat polymorphism and isolated hypospadias were calculated using a random-effects model. Subgroup analyses were performed by race, study design, sample for DNA extraction, and hypospadias classifications. This meta-analysis included 6 case-control studies, including 444 isolated hypospadias cases and 727 controls. The results showed that patients with isolated hypospadias had longer CAG repeats in their androgen receptor gene sequence (weighted mean difference = 1.36, 95% confidence interval = 0.60-2.13; P = 0.0005). Similarly, stratified analyses also detected significant associations in all subgroups, excluding the group with severe hypospadias (weighted mean difference = 0.35, 95% confidence interval = -0.42-1.12; P = 0.38). This meta-analysis indicated that longer CAG repeats were 1581 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (1): 1580-1588 (2015 CAG repeat polymorphism and isolated hypospadias associated with the risk of isolated hypospadias, and that longer CAG polymorphisms may be related to the etiology of isolated hypospadias. Future studies based on Asian and African-American patients should be performed to re-evaluate this association.

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Hypospadias: Interactions between environment and genetics

Cited by 93 publications

References 128 publications

Homosexuality as a Consequence of Epigenetically Canalized Sexual Development

Homosexuality as a Consequence of Epigenetically Canalized Sexual Development

Current understanding of hypospadias: relevance of animal models

Androgen receptor gene CAG repeat polymorphism and risk of isolated hypospadias: results from a meta-analysis

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