停留精巣の未来を探る : 精巣下降の分子生物学

Abstract

The mechanism of testicular descent is multifactorial, and the process is known to occur in two steps accompanied by different anatomies and hormonal regulation. In the first step, the testis descends from the lower pole of the kidney to the pelvic cavity near the bladder neck as a result of the swelling reaction of the gubernaculum. Next, in the second step, the testis descends into the scrotum through the inguinal canal via the gubernacular migration. The first step is androgen-independent, whereas the second step depends on the androgen action. Recently, several molecular studies on testicular descent have been reported. Several factors, such as androgen, calcitonin gene-related peptide (CGRP), epidermal growth factor (EGF), Hoxa-10 and insulin-like factor 3 (INSL3) have been suggested to be possible regulators of testicular descent. Because cryptorchidism has been frequently shown in androgen-insensitive human and mice (TFM-mice), androgen has been thought to play an important role in testicular descent. CGRP, which is released from the genitofemoral nerve, has been suggested to mediate the inguinoscrotal testicular descent. The epidermal growth factor (EGF) may promote both testosterone-induced wollfian duct differentiation and testicular descent by activating the androgen responsive systems. In male mice, a targeted disruption of the HOXA 10 gene causes cryptorchidism and the cryptorchid testes in these mutant mice are located in the lower abdominal cavity, whereas the cryptorchid testes in male mice lacking the INSL3 gene or its receptor Lgr8 were located in the abdominal cavity high. Recently, estrogens or environmental endocrine disruptors have also been suspected to induce a down-regulated INSL3 expression and thus disturb testicular descent.