Endocrine Abstracts

Reproductive disorders in males that manifest at birth (cryptorchidism, hypospadias), or young adulthood (low sperm count, lower testosterone levels, testicular cancer) may share a common origin and constitute a ‘testicular dysgenesis syndrome’ (TDS). Normal reproductive tract development is programmed by androgens within the ‘masculinisation programming window’ (MPW, e15.5–e18.5-rats; ~8–14 weeks’ gestation-humans). In rats, TDS disorders ca...

From human epidemiological and related studies, there is strong (indirect) evidence that common male reproductive disorders that manifest at birth (cryptorchidism, hypospadias) or in adulthood (low sperm count, low testosterone, primary hypogonadism) may have a common origin in foetal life due to impaired androgen (testosterone) production or action; the so-called testicular dysgenesis syndrome (TDS) hypothesis. Whilst the foetal origin of cryptorchidism and hypospadias is sel...

Background: Fetal glucocorticoid overexposure is associated with low birthweight and increased cardiovascular disease risk in the offspring. Such ‘programmed effects’ can be transmitted across generations through both male and female lines. Disruption of a germline epigenetic reprogramming pathway, characterised by genome-wide erasure and subsequent re-establishment of DNA methylation, may underpin the intergenerational transmission of programmed effects. We used a r...

Fetal Leydig cell (LC) dysfunction leads to human male reproductive disorders (‘testicular dysgenesis syndrome’; TDS) that manifest at birth (cryptorchidism, hypospadias) or in young adulthood (low sperm count, testicular germ cell cancer). The factors regulating fetal LC function in early gestation are unknown, but can be disrupted in rats by environmental chemicals (e.g. dibutyl phthalate (DBP)). We identify a novel repressor mechanism that explains this vulnerabil...

Background: Endocrine disruption in the human fetal testis by environmental agents has been proposed as a possible cause of testicular dysgenesis syndrome (TDS) comprising male reproductive disorders such as testicular germ cell tumours (TGCT), cryptorchidism, hypospadias and low sperm counts. Exposure of fetal rats to the widely used plasticizer di(n-butyl) phthalate (DBP) results in a TDS-like syndrome due to a reduction in testosterone production. Whether such effects also ...