Apoptotic cell death and fertility in three unilateral cryptorchid rat models

Abstract

Three rat strains have been studied, using a sensitive apoptotic detection method for germ-cell degeneration, to resolve the controversy regarding the effect of cryptorchidism on the contralateral descended testis (CDT). Sprague Dawley and Buffalo rats were made cryptorchid by operation at 20-22 days of age, while trans-scrotal (T-S) rats were a congenitally unilateral cryptorchid strain. Sham operated rats or normal T-S littermates were used as controls. Experiments were performed over a period ranging from 2 weeks to 18 months. Testis weight was assayed, as was the detection of apoptosis by agarose gel laddering and immunohistochemistry by using the TUNEL method. Labeled cells in 150 cross-sectioned testis tubules were counted on the TUNEL stained slides and the mean number of labeled cells per tubule was calculated. Paternity studies on Sprague Dawley and T-S rats were carried out at 12 and 24 weeks of age to assess fertility by the resultant number of pregnancies and litter sizes. Both Sprague Dawley and T-S rat models showed a biphasic distribution of apoptosis levels. This biphasic distribution was not observed in Buffalo rats as they were only studied at later time points (12-20 weeks). A significant effect on either testis weight or apoptosis in the CDT compared with the control descended testis (P > or = 0.1) has not been found in these three cryptorchid models, and the present results are discussed with reference to observations of other researchers in rodents and humans. While the cryptorchid testis showed a high level of labeled apoptotic cells per tubule in all rat strains, fertility was not affected and remained the same as controls at 12 and 24 weeks. There was, however, a marked strain difference in fertility in T-S as compared with Sprague Dawley rats. After 24 weeks of cryptorchidism, both control and cryptorchid T-S rats had a 44% pregnancy incidence compared with a 90% pregnancy incidence in Sprague Dawley rats. In addition, litter size in T-S control and cryptorchid rats were small compared with those of Sprague Dawley rats at 12 and 24 weeks.

Abdominal Temperature Induces Region-Specific p53-Independent Apoptosis in the Cauda Epididymidis of the Mouse1

“…Our results show that temperature is indeed one factor that can trigger apoptosis in the cauda epididymidis. Temperature-induced apoptosis has already been described in the testes in cases of cryptorchidism, both spontaneous and experimental [37][38][39][40]. It is noteworthy that, in our case, this temperatureinduced apoptosis was region dependent, being restricted to the proximal tubules of the cauda.…”

Physiological and Pathological Cell Deaths in the Reproductive Organs.

“…Germ cells in both types of gonads are very sensitive to pathological stimuli. It has been reported that testicular germ cell degeneration occurs during various stages of spermatogenesis under experimentally manipulated conditions, such as cryptorchidism (Shikone et al, 1994;Yin et al, 1998;Watts et al, 2000;Xu et al, 2000), ischemia-reperfusion (Turner et al, 1997;Shiraishi et al, 2000;Koji et al, 2001), hypophysectomy (Russell and Clermont, 1977), treatment with GnRH antagonists (Billig et al, 1995;Hikim et al, 1995), heating (Yamamoto et al, 2000;Miura et al, 2002), and drug treatment (Nonclercq et al, 1996;Lee et al, 1997;Nandi et al, 1999;Franca et al, 2000;Zhu et al, 2000;Yu et al, 2001). In addition, Nandi et al reported that reduction of intratesticular testosterone due to Leydig cells degeneration by treatment with ethane 1,2-dimethanesulfonate (EDS) indirectly induces germ cell apoptosis (Nandi et al, 1999).…”

Influence for testicular development and histological peculiarity in the testes of flutamide‐induced cryptorchid rat model

“…4 No spermatids, few spermatocytes, arrest of spermatogenesis at the primary spermatocyte stage. 3 Spermatogonia only. Mothers of the control rats were injected in utero with only the vehicle, and those of the model rats were treated with 2.5-15 mg flutamide per day per body on gestation days 14-20.…”

“…Recently, Zimmermann et al 10 described the Insl3 knockout mouse as cryptorchid animal model, and Overbeek et al 11 also reported the transgenic mouse model. To our knowledge, most of the experimental animal models for cryptorchidism have been made by surgical methods, [3][4][5][6][7] that is, displacement of the normal descended testes. By such methods, however, the influence of the surgical stress on testicular tissue could not be completely denied.…”