Genital anomalies in human and animal models reveal the mechanisms and hormones governing testicular descent

Abstract

A systematic examination of the conditions characterized by the presence of genital anomalies in humans, noting in each condition the position of the gonad, the nature of the gubernaculum and cranial suspensory ligament can provide valuable information regarding the mechanisms controlling the final position of the gonads. In conditions where MIS is absent, the gubernaculum is "feminized', resulting in a testis in the position normally occupied by an ovary or an abnormally mobile testis that can prolapse to the inguinal region. In conditions of androgen insensitivity the testis is located in the inguinal region, indicating that the first phase of descent is normal but that inguinoscrotal descent has failed to occur. Ovarian descent fails to occur in congenital adrenal hyperplasia, despite exposure of the developing fetus to high levels of androgens, indicating that androgen alone does not control gonadal descent. Moreover, ovarian descent fails to occur despite androgen-dependent regression of the cranial suspensory ligament. The correlation between the degree of Müllerian duct retention and scrotal position in mixed gonadal dysgenesis further strengthens the hypothesis that the first stage of testicular descent is controlled by MIS. The study of genital anomalies suggests that MIS controls the swelling reaction in the male gubernaculum, which is responsible for the first phase of testicular descent to the inguinal region. The second or inguinoscrotal phase of descent is androgen-dependent. Regression of the cranial suspensory ligament is also androgen-dependent: however, it is the gubernaculum and not the presence or absence of the cranial suspensory ligament which controls testicular descent. A combined knowledge of the hormonal basis controlling sexual differentiation and the biphasic model of testicular descent enables the clinician to accurately predict the internal anatomy of these complex sexual anomalies.