Ectopic expression of FGF-3 results in abnormal prostate and Wolffian duct development

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Abstract
To evaluate the effects of FGF-3 expression in the prostate and male reproductive tract, we employed a bitransgenic system to target FGF-3 to these organs. We present a first study that ectopic FGF-3 expression resulted in exuberant hyperplasia of all bigenic prostatic lobes typified by epithelial stratification, cribiform structures and papillary tufts. These cells displayed increased nuclear-to-cytoplasmic ratios and bromodeoxyuridine (BrdU) proliferative index but retained relatively uniform nuclear androgen receptor (AR) and the tumor suppressor C-CAM1 staining. Furthermore, the dysmorphogenic prostatic cells also resembled PIN (prostatic intraepithelial neoplasia)-like lesions but did not appear to have invaded the basal lamina. In addition to these phenotypes, profound disorders of the bigenic Wolffian duct derivatives were observed. The bigenic ampullary glands and vas deferens were extremely cystic, hypertrophic and hyperplastic; the enlarged epididymi showed a reduction of spermatozoa and the seminal vesicles exhibited a dramatic reduction of seminal secretions. Because of these severe abnormalities, these infertile males presented with diaphragmatic hernias, hemoperitoneum and many secondary abnormalities at sacrifice. Taken together, we show that ectopic FGF-3 expression severely perturbs normal prostate development and our system should be useful for the analyses of early changes in prostatic hyperplasia.