06-P053 ENT3, mutated in H syndrome, is required for proper heart formation

The commonest reproductive disorders in human males at birth (cryptorchidism, hypospadias) or young adulthood (low sperm counts, testis germ cell cancer) may comprise a ‘testicular dysgenesis syndrome’ (TDS) resulting from fetal testis dysfunction. We and others have developed an animal model for TDS, involving in utero exposure of pregnant rats to di-n-butyl phthalate (DBP), which is a common ingredient in plastics, pharmaceuticals and personal care products. Male DBP-exposed offspring exhibit a high incidence of cryptorchidism, hypospadias and infertility in adulthood and abnormal development/function of the germ cells and somatic (Leydig, Sertoli) cells in fetal life. However, there are still huge gaps in the understanding about fundamental aspects of TDS; in particular its causes, especially the potential role of exposure to common environmental chemicals, the timing and mechanism of TDS induction and what determines risk of adult onset TDS disorders. The overall aim of this study is to establish the mechanistic pathways via which mild disruption of fetal testicular development leads to TDS in humans. For this purpose, testes of rat embryos of different developmental ages (e14.5–e19.5) were isolated from pregnant rats treated with control vehicle or DBP (500 mg/kg/day) from e13.5. We investigated the temporal and spatial expression patterns for genes which have previously been shown to be important in testis development in the mouse, using TaqMan real-time PCR and whole mount insitu hybridization. We hypothesize that some of this ‘key testicular genes’ show abnormal expression in DBP-treated testes, which could be a causation for TDS development.