Title:
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New insights into androgen-dependent Wolffian duct development
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The aims of the current study were to investigate the timing and mechanisms involved in androgen mediated WD development. The present study exposed pregnant rats to the androgen receptor antagonist, flutamide (50 or 100 mgkg-1) which reduces testicular testosterone production, and/or exogenous testosterone during specific time windows in fetal life in order to establish the key time windows for androgen-regulated WD development and the possible mechanisms involved. These studies confirmed the vital role for the androgens in WD development and highlighted their critical involvement in establishing the early patterning of WD development between e15.5-17.5, prior to any sign of morphological differentiation. In conclusion, androgens alone appear to be sufficient for WD development but in their absence, a compensatory mechanism may try to rescue the male WD. Fetal WD differentiation is far more susceptible to blockade of fetal androgen action than is its initial stabilisation although these effects appear to be mediated by disruption of stromal-epithelial interactions during the stabilisation period. Persistence of WD-derived structures postnatally is also affected, however, this is likely to be due to impaired patterning of the fetal Wolffian duct rather than prevention of initial stabilisation. These findings have identified the critical window for androgen action in the WD and thus have created an opportunity to study the elusive mechanisms behind androgen action. Since androgens act on many other systems in the body with many parallels existing between the male and female reproductive system, the outcomes of these studies may therefore impact on our understanding of WD development but also of other androgen-dependent processes such as the development, function and diseases of other reproductive tissues.
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