Associations among hypospadias, cryptorchidism, anogenital distance, and endocrine disruption

Hsieh, Michael H.; Breyer, Benjamin N.; Eisenberg, Michael L.; Baskin, Laurence S.

doi:10.1007/s11934-008-0025-0

Cited by 184 publications

(164 citation statements)

References 29 publications

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“…There was also a trend for a shorter anogenital distance in boys with incomplete testis descent. In a cohort of boys with hypospadias or cryptorchidism, the anogenital distance quantified as anterior and posterior anoscrotal distance and measured at the time of surgery was significantly shorter in hypospadias but not in cryptorchid boys compared with normal boys (52).…”

Section: Environmental Factorsmentioning

confidence: 88%

Factors controlling testis descent

Hughes¹,

Acerini²

2008

European Journal of Endocrinology

136

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Descent of the testis from an intra-abdominal site in foetal life to an extracorporeal location after birth is a mandatory developmental process to ensure that the mature testis promotes normal spermatogenesis. The two phases of transabdominal and inguinoscrotal descent occur approximately during the first and last thirds of gestation respectively. Key anatomical events to release the testis from its urogenital ridge location and to guide the free gonad into the scrotum are the degeneration of the cranio-suspensory ligament and a thickening of the gubernaculum. Androgens play a role in both these processes, particularly with respect to enabling the testis to traverse the inguinal canal in the final phase of descent. Experiments in animals suggest that androgens mediate this effect via the release of calcitonin gene-related peptide by the genitofemoral nerve, but direct evidence for such a mechanism is lacking in humans. The transabdominal phase of descent is under the control of insulinlike 3 (INSL3), a product of the Leydig cells. Definitive evidence of its role in rodent testis descent is illustrated by the phenotype of bilateral cryptorchidism in Insl3K/K null mice. Circulating levels of INSL3 are higher in boys at puberty, are undetectable in girls and are lower in boys with undescended testes. A minority also have a mutation either in the INSL3 gene or affecting its receptor gene, relaxin/insulin-like family peptide receptor 2 (LGRF8). Other factors that may play a role in testis descent include the anti-Mullerian hormone and members of the HOX gene family. Evidence that the prevalence of undescended testis may be increasing provides a phenotypic readout for the effects of postulated chemicals in the environment interfering in some way with the action of factors that control testis descent. Epidemiological studies point to profound geographical variations in prevalence in countries such as Denmark and Finland. Associations have been found with levels of chemicals labelled as endocrine disruptors being higher in breast milk samples from mothers with cryptorchid boys when compared with controls. The adverse effects of these compounds (e.g. bisphenol A) can be replicated in the offspring of dams exposed during pregnancy. A sensitive marker of an anti-androgen effect of a compound is a reduction in the anogenital distance, an anthropometric measurement that is significantly greater in males compared with females. The observation of an association between the anogenital distance in infant boys and the level of pesticides in the urine of their mothers in late gestation indicates that this has the potential to be a useful surrogate marker of the effects of environmental chemicals on testis descent in human population studies. The rightful place for the testis at birth is in the scrotum in order to provide the temperature differential essential for normal spermatogenesis. Appropriate screening programmes and early surgical intervention are the prerequisites to ensure optimal fertility in adulthood and a con...

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Section: Environmental Factorsmentioning

confidence: 88%

Factors controlling testis descent

Hughes¹,

Acerini²

2008

European Journal of Endocrinology

136

View full text Add to dashboard Cite

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“…Anogenital distance, a reflection of male reproductive tract development which is reduced in hypospadiac patients [75], was found to be reduced in cases of prenatal exposure to phtalates [75,76].…”

Section: Ii-1 Arguments For An Environmental Contributionmentioning

confidence: 93%

Hypospadias: Interactions between environment and genetics

Kalfa

Philibert

Baskin

et al. 2011

Molecular and Cellular Endocrinology

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“…Hsieh et al, (2008) revealed that boys having less anogenital distance have genital anomalies (i.e. Cryptorchidism and Hypospadias) establishing a link between normal genital development (Hsieh et al, 2008). Another aspect of this study was a chromosomal assay of the infertile males, which showed that infertile males had a higher frequency of numerical as well as structural aberrations as compared to normal healthy males which are an important indicator towards infertility.…”

Section: Resultsmentioning

confidence: 78%

“…In other research work published in the same year by Michael Eisenberg et al, revealed that fatherhood is associated with the longer AGD and may predict the normal male potential and AGD was significantly correlated with total motile sperm count and with sperm density (Michael et al, 2011). Hsieh et al, (2008) revealed that boys having less anogenital distance have genital anomalies (i.e. Cryptorchidism and Hypospadias) establishing a link between normal genital development (Hsieh et al, 2008).…”

Section: Resultsmentioning

confidence: 90%