Endocrine Abstracts

Disorders of male reproductive health, including testicular cancer, cryptorchidism, hypospadias and low sperm counts, are common and may be increasing in incidence. These conditions manifest at different life stages (low sperm counts and testicular cancer in adulthood; cryptorchidism and hypospadias at birth) but are proposed to originate in fetal life. These disorders have therefore been hypothesized to comprise a ‘testicular dysgenesis syndrome’ (TDS), which result...

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...

Context: In rodents, in-utero exposure to the exogenous oestrogen diethylstilboestrol (DES) results in reproductive abnormalities in male offspring. It has been proposed that similar anti-androgenic effects also occur in the human fetal testis following oestrogen exposure.Objective: Determine effects of DES exposure on testosterone production by normally growing human fetal testis xenografts.Design: Human fetal testes (15&...

Fetal events can affect adult testosterone levels but how this occurs is unknown, as adult Leydig cells (ALC) do not differentiate until puberty. Qin et al. 2008 (PLos ONE) identified that chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) is essential postnatally for ALC development. We hypothesized that: i) COUP-TFII+ non-Leydig interstitial cells are progenitors for ALC and are present in the fetal testis, ii) these ‘pr...

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 ...