Genetic, Maternal, and Environmental Risk Factors for Cryptorchidism: An Update

TY - JOUR

T1 - Genetic, Maternal, and Environmental Risk Factors for Cryptorchidism

T2 - An Update

AU - Barthold, Julia Spencer

AU - Reinhardt, Susanne

AU - Thorup, Jorgen

N1 - Georg Thieme Verlag KG Stuttgart · New York.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Unilateral or bilateral cryptorchidism is an isolated anomaly in the majority of cases, with evidence to date suggesting that it is a complex disorder resulting from interactions between genetic and environmental factors. Population, family, and limited genome-wide association data suggest moderate genetic risk, multiple susceptibility loci, and a role for the maternal environment. Epidemiologic studies have identified low birth weight or intrauterine growth retardation as factors most strongly associated with cryptorchidism, with additional evidence suggesting that maternal smoking and gestational diabetes increase risk. Animal studies have shown that the testis regulates its own descent by secretion of hormones that stimulate differentiation of the gubernaculum, and that endocrine-disrupting chemicals (EDCs) exhibit antiandrogenic and/or estrogenic activity that alters testicular function or gubernacular response to hormonal stimulation. However, we have yet to determine the degree to which EDCs contribute to cryptorchidism risk in humans, in part due to the varying methodology used in epidemiological and exposure studies. Large populations will be required to define the gene-environment interactions that predispose to cryptorchidism, in view of multiple small effect genetic susceptibility loci, ubiquitous exposure to mixtures of EDCs, and possible epigenetic effects. The present review provides an update of potential genetic and environmental risk factors for cryptorchidism, and future work required to better understand the etiology of this common and complex disease.

AB - Unilateral or bilateral cryptorchidism is an isolated anomaly in the majority of cases, with evidence to date suggesting that it is a complex disorder resulting from interactions between genetic and environmental factors. Population, family, and limited genome-wide association data suggest moderate genetic risk, multiple susceptibility loci, and a role for the maternal environment. Epidemiologic studies have identified low birth weight or intrauterine growth retardation as factors most strongly associated with cryptorchidism, with additional evidence suggesting that maternal smoking and gestational diabetes increase risk. Animal studies have shown that the testis regulates its own descent by secretion of hormones that stimulate differentiation of the gubernaculum, and that endocrine-disrupting chemicals (EDCs) exhibit antiandrogenic and/or estrogenic activity that alters testicular function or gubernacular response to hormonal stimulation. However, we have yet to determine the degree to which EDCs contribute to cryptorchidism risk in humans, in part due to the varying methodology used in epidemiological and exposure studies. Large populations will be required to define the gene-environment interactions that predispose to cryptorchidism, in view of multiple small effect genetic susceptibility loci, ubiquitous exposure to mixtures of EDCs, and possible epigenetic effects. The present review provides an update of potential genetic and environmental risk factors for cryptorchidism, and future work required to better understand the etiology of this common and complex disease.

U2 - 10.1055/s-0036-1592416

DO - 10.1055/s-0036-1592416

M3 - Review

C2 - 27642851

SN - 0939-7248

VL - 26

SP - 399

EP - 408

JO - European Journal of Pediatric Surgery

JF - European Journal of Pediatric Surgery

IS - 5

ER -