Pediatric Urology Research Lab

The main focus of our lab is improved understanding of the causes of cryptorchidism, or undescended testis, which is a common problem presenting at birth or later in childhood and affecting 3%-4% of males.

Cryptorchidism is associated with other reproductive tract and developmental abnormalities and also has significant long-term health concerns associated with sterility and testicular cancer. There is strong evidence for a genetic contribution to cryptorchidism susceptibility based on familial clustering.

Our studies are focused on:

• Identifying the genes that contribute to the risk of cryptorchidism in boys
• Studying a natural rat model of cryptorchidism that also seems to involve variants in multiple genes to help determine common biological pathways and mechanisms that contribute to susceptibility to cryptorchidism

Currently, our human and rat data suggest involvement of developmental genes involved in cytoskeleton regulation, muscle, and neural pathways, and in addition, may support a role for genes involved in target-specific androgen receptor signaling. In analyzing linkage and expression data from our cryptorchid rat model, we have identified gene candidates that will require validation in functional studies.

Using selective breeding of wild type rat strains for variants in these candidates, we have generated de novo cryptorchidism for the first time. By generating the cryptorchid phenotype in rats with different genetic backgrounds, we will map the risk variants and then use in vitro tools to analyze alleles of interest to define their biological roles in the cryptorchid phenotype. We anticipate that parallel studies of rat and human cryptorchid models will inform each other in our efforts to understand the pathogenesis of failed descent, subfertility, and malignancy in cryptorchidism.