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 results from dysfunction of the Leydig (LC) and/or Sertoli cells (SC) in the fetal testis and is associated with low testosterone levels.

Fetal exposure of male rats to DBP induces testicular changes similar to TDS in humans, including the formation of focal ‘dysgenetic areas’ within postnatal testes, surrounded by otherwise normal tubules exhibiting complete spermatogenesis. We hypothesize that these dysgenetic areas arise when SCs (and other cell types) get ‘trapped’ during the abnormal formation of large LC clusters in fetal life and by postnatal d4 these groups of intermingled cells attempt to from seminiferous tubules. It is likely that the malformed tubules that result correspond to the dysgenetic areas evident in later life

To test this hypothesis, we evaluated the effect of short-term DBP-exposure from e19.5–e21.5 (after the seminiferous cords have formed). This treatment regime induces similar testicular changes to longer term (e13.5–e21.5) DBP treatment, including decreased fetal testosterone levels, multinucleated germ cells and LC aggregation, though the latter is less pronounced than after longer term treatment. In contrast to the latter, few if any ‘extra-tubular’ SCs are found at e21.5. By postnatal day 4 there is little evidence of the large groups of intermingled cells attempting to form tubules, and by adulthood there is no evidence of dysgenetic areas within the DBP-exposed animals. These results provide support for our hypothesis as to the origin of dysgenetic regions within testes of DBP-exposed animals.