Comparative studies of fertility and histologic development of contralateral scrotal testes in two rat models of unilateral cryptorchidism

Abstract

Fertility and the development of the contralateral scrotal testis in patients with unilateral cryptorchidism (UCO) remain controversial. This study investigated these controversies in two different UCO rat models using 43 Wistar King A rats. The animals were divided into three groups: I: an endocrinologic model of UCO was obtained by injecting pregnant dams with flutamide 100 mg/kg per day on days 15-17 of gestation (n = 12); II (n = 21): a mechanical model of UCO was obtained by extra-abdominal fixation of the gubernaculum in the neonatal period, III (n = 10): non-treated rats were used as controls. At the age of 90 days, 5 rats from each group were segregated into individual cages and housed with two virgin adult females for 2 weeks. The occurrence of pregnancy and litter sizes were counted in order to study fertility. All the animals were then weighed and killed. The occurrence of testicular descent, growth of the external genitalia, and epididymal development were examined. Morphologic and histologic evaluations were performed in the cryptorchid and contralateral testes. In the endocrinologic model (group I) the 10 female rats failed to show any offspring (0%), while in the mechanical model (group II) 9 out of 10 rats had offspring (90%, P < 0.001); 10 out of 10 control rats showed offspring. All of the rats in groups I and II had UCO, and the undescended testes were located in the superficial inguinal position, while the contralateral and control testes descended into the scrotum. Hypospadias and a small epididymis were frequently noted in the flutamide-treated rats. Testicular weight, seminiferous tubular diameter, and spermatogenesis were all significantly reduced in the undescended testes (UDT) compared to the contralateral and control testes. Moreover, the development of the contralateral testis was inhibited in group I compared to groups II and III. Our observations showed that short-term exposure to flutamide in utero induced significantly reduced fertility and degenerated contralateral scrotal testes in UCO rats compared to mechanically-induced UCO rats by early adulthood. It is suggested that fertility potential and testicular development in unilateral UDT may be partially due to the factors that induce testicular maldescent, especially in cases due to intrauterine hormonal abnormalities. These cases may show inhibited fertility and testicular development even after orchiopexy.