The effect of oestrogen and testosterone on the urethral seam of the developing male mouse genital tubercle

Abstract

OBJECTIVES: To describe the effects of exogenous oestrogens and androgens on urethral formation in the mouse, as the development of the mouse and human urethra have significant similarities, and understanding normal male urethral development may help to identify the causes of abnormal development, e.g. hypospadias. MATERIALS AND METHODS: Timed-pregnant C57/6 mice were exposed to synthetic oestrogens and androgens. The morphology of the genital tubercles was examined histologically and with three-dimensional computer reconstruction. Specific attention was focused on the developing urethral seam. RESULTS: Microscopic serial analysis confirmed the presence of an arrest in seam formation in about half of oestrogen-treated male fetuses. In contrast, there was acceleration of urethral fold fusion and a longer urethral tube in those treated with androgens. Oestrogen-treated fetuses had a thin periurethral spongiosa, in contrast to androgen-treated fetuses which developed a thicker periurethral spongiosa. The effect of oestrogens on seam area formation did not depend on the dose, but in contrast, in the androgen-treated fetuses it was. CONCLUSION: Oestrogens and androgens have a direct effect on the fusion of the urethral fold that leads to seam formation. Normal urethral development depends on the delicate balance of these complementary hormones.