Flutamide-Induced Testicular Undescent in the Rat is Associated with Alterations in Genitofemoral Nerve Morphology

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Abstract
Androgen regulation of testicular descent is an established fact. However, the mechanisms by which androgens assert their influence is unknown. One of the leading hypotheses regarding androgenic control of testicular descent is based upon the assumption that testosterone regulates the development of the sexually dimorphic genitofemoral nucleus and nerve (GFN). To investigate whether or not alterations in the genitofemoral nerve are indeed androgen dependent and associated with testicular undescent, we administered flutamide in a time-specific manner to pregnant Sprague-Dawley rats. The GFN of ten animals with unilateral intra-abdominal testicular undescent was compared with the contralateral GFN associated with the descended testicle. Digital microscopic evaluations found that the GFN associated with testicular undescent did express altered morphologic abnormalities. Specifically, the GFN associated with the cryptorchid testicle had significant reductions in the neural diameter (.0169 +/- .0024 mm.2 versus .0275 +/- .0079 mm.2; p < .01), the number of large myelinated fibers per mm.2 (8.4 +/- 3.3 versus 18.8 +/- 5; p < .001) and the number of small myelinated nerve fibers per mm.2 (632 +/- 87.4 versus 1090.7 +/- 104.3; p < .001). These data suggest that testicular undescent in the rat is associated with morphologic alterations in the ipsilateral genitofemoral nerve. The exact mechanism of how these alterations are related to cryptorchidism remains to be elucidated.