Urologic Diseases Research Updates
Scientists Catalog Genes Expressed during Urogenital Development
Normal urogenital development is dependent on a network of Wnt7a-associated genes, according to scientists funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) who examined gene expression of mice during prenatal days 13 and 14. The study provides reference data for future efforts aimed at understanding and preventing urogenital birth defects.
“Congenital anomalies of the urogenital tract are the third most common birth defects, with abnormalities of the external genitalia being the most prevalent manifestation,” wrote Melissa H. Little, Ph.D., a professor at Queensland University, Australia, and co-authors in the August 15, 2010, issue of Developmental Biology. Despite the clinical relevance and prevalence of these defects, very little research has addressed the genetic basis for urogenital development.
Common genital birth defects include undescended testicles and hypospadias—a condition in which the urethral outlet is located along the shaft of the penis instead of at the end. The two conditions affect as many as one in 125 males and are becoming increasingly prevalent, possibly due to prenatal exposure to environmental compounds that bind male hormone receptors. Less common conditions include micropenis, an extremely small penis, and diphallia, the presence of two penises. For those affected, genital birth defects create social and reproductive challenges.
The scientists removed bladder and urethral tissue from mice at prenatal days 13 and 14. They then used DNA microarrays to screen for hundreds of gene products and identify the most actively expressed genes. After building a “catalog” of gene activity, the team identified 31 genes in the genital tubercle—the yet unformed tissue node destined to become the external genitalia—that are potentially critical for normal development. Of note were genes associated with the Wnt7a gene network, which is important in craniofacial and limb development. Several of the genes in the network are known to be influenced by sex hormones, suggesting potential routes by which environmental factors could disrupt normal development.
“This study describes the creation and analysis of the first comprehensive catalog of gene expression profiles describing the early murine lower urinary tract and genital tubercle,” wrote Little and co-authors. Combined with existing data that catalogs later stages of urogenital development, “this will be a valuable resource for investigating the molecular basis of morphogenesis in this organ system and to investigate correlations between development and disease.”
The National Kidney and Urologic Information Clearinghouse, part of the NIDDK, has fact sheets and easy-to-read booklets about urologic disorders. For more information or to obtain copies, visit www.urologic.niddk.nih.gov.
NIH Publication No. 11–5743