Cryptorchidism, the absence in the scrotum of one or both testes (usually because of the failure of the testis to descend), and hypospadias, the abnormal positioning of the opening of the urethra, are common birth defects of the male genitalia and are risk factors for the adult-onset disorders of low sperm count and testicular cancer. Although it is known that "male" hormones, in particular testosterone, drive the pathway that leads to a fetus becoming a male (including the development of the male genitalia), the cause of defects in this process is unclear. However, Michelle Welsh and colleagues at The Queen's Medical Research Institute, United Kingdom, have now determined that in rats, the "male" hormones drive the decision to become a male during a window of time before the male genitalia develop. During this period of time, blocking the action of "male" hormones led to cryptorchidism and hypospadias, and these defects were associated with a decrease in the distance between the anus and the genitalia (AGD). Based on the timing in rats, the authors believe that the equivalent window in humans is likely to be 8-14 weeks of gestation. Furthermore, they suggest that measuring AGD in neonatal humans could provide a noninvasive method to predict neonatal and adult reproductive disorders (cryptorchidism and hypospadias, and low sperm count and testicular cancer, respectively).
TITLE: Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism
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