Genetic and environmental contributors to cryptorchidism

Cryptorchidism is a common congenital anomaly that shows familial clustering and increased prevalence in first-degree relatives, suggesting that genetic factors contribute to the etiology. Animal models and some human data suggest that environmental exposures may also contribute to risk. Potential variables during development that may contribute to the occurrence of cryptorchidism in the genetically susceptible individual include maternal hormonal influences as well as other environmental factors that affect hormonal signaling. In a subset of affected males, genetic and/or environmental factors may also contribute to associated infertility and malignancy. This review will discuss the limited state of knowledge regarding the etiology of non-syndromic cryptorchidism. Non-syndromic cryptorchidism is a common and complex disorder of un known etiology with geographic and perhaps temporal variability (1,2). Although presumed to be multifactorial in etiology, few specific genetic or environmental factors have been clearly linked to the disease in man. Hormonal pathways that participate in testicular descent and the effects of chemical exposures on this process have been studied in animal models. In man (3-5) and animal strains with cryptorchidism (6,7), there is evidence for multilocus genetic susceptibility. However, despite promising gene candidates, few genomic variants have been linked to non-syndromic cryptorchidism. Humans are exposed to a wide variety of potentially anti-androgenic and/or estrogenic environmental chemicals, but the degree to which these may contribute to the pathogenesis of cryptorchidism is not clearly known. Potential factors that may contribute to the etiology of cryptorchidism are discussed.