Testicular Dysgenesis and Fetal Origins (#86)
The incidence of Testicular Dysgenesis Syndrome (TDS) which comprises disorders including hypospadia, cryptorchidism, testicular cancer and low sperm counts has increased over the last few decades. Defects in early testis development have been implicated in the aetiology of TDS. TDS results from disruption of gonadal development during fetal life and the biological pathways that are affected are not fully clear. Using transgenic mouse models, gene expression analysis, immunhistochemistry, immunofluorescence and gonad culture techniques, we are investigating fetal events essential for future adult testis development. We have found that TGFBR3 (betaglycan), a TGFb superfamily co-receptor, is essential for seminiferous cord and Leydig cell development in the fetal mouse testis. To investigate the mechanism of betaglycan’s action we cultured testes from the betaglycan knockout and the wildtype mouse with or without the ligand TGFb2. We found that TGFb2 rescues the compromised cord development observed due to the loss of betaglycanin the differentiating fetal testis,but does not compensate for the reduction in steroidogenesis. Using green fluorescing protein (GFP) mice in assembled gonad cultures we were able to identify defects in cell migration from a wildtype green mesonephros into a betaglycan knockout testis. This data indicates that the loss of betaglycan affects cell migration from the mesonephros into the gonad. Our goal is to further understand the genetic regulation of processes essential for testis development such as cell migration, steroidogenesis, reproductive duct formation and cell death. Our studies will yield a better understanding of the impact of early fetal testis dysgenesis on future adult testis health.