EDCs and male urogenital cancers

Male sex determination and sexual differentiation occur between 6-12 weeks of gestation. During the "male programming window" the fetal testes start to produce testosterone that initiates the development of the male reproductive tract. Exposure to endocrine disrupting chemicals (EDCs) able to mimic or disrupt steroid hormone actions may disrupt testicular development and adversely impact reproductive health at birth, during puberty and adulthood. The testicular dysgenesis syndrome (TDS) occurs as a result inhibition of androgen action on fetal development preceding Sertoli and Leydig cell dysfunction and may result from direct or epigenetic effects. Hypospadias, cryptorchidism and poor semen quality are elements of TDS, which may be considered a risk factor for testicular germ cell cancer (TGCC). Exposure to estrogen or estrogenic EDCs results in developmental estrogenization/estrogen imprinting in the rodent for prostate cancer (PCa). This can disrupt prostate histology by disorganization of the epithelium, prostatic intraepithelial neoplasia (PIN) lesions, in particular high-grade PIN (HGPIN) lesions which are precursors of prostatic adenocarcinoma. These defects persist throughout the lifespan of the animal and later in life estrogen exposure predispose development of cancer. Exposure of pregnant dams to vinclozolin, a competitive anti-androgen, and results in prominent, focal regions of inflammation in all exposed animals. The inflammation closely resembles human nonbacterial prostatitis that occurs in young men and evidence indicates that inflammation plays a central role in the development of PCa. In conclusion, in utero exposure to endocrine disrupters may predispose to the development of TDS, testicular cancer (TCa) and PCa and are illustrations of Developmental Origins of Health and Disease (DOHaD).