Rat models of post‐irradiation recovery of spermatogenesis: interstrain differences

Abstract

Recently we reported large differences between rat strains in spermatogenesis recovery at 10 weeks after 5-Gy irradiation suggesting that there are interstrain as well as interspecies differences in testicular radiation response. To determine whether these interstrain differences in sensitivity might be a result of the particular dose and time-point chosen, we performed dose-response and time-course studies on sensitive Brown-Norway (BN) and more resistant spontaneously hypertensive (SHR) and Sprague-Dawley (SD) rats. Type A spermatogonia were observed in atrophic tubules at 10 weeks after irradiation in all strains indicating that tubular atrophy was caused by a block in their differentiation, but the doses to produce the block ranged from 4.0 Gy in BN to 10 Gy in SD rats. Although the numbers of type A spermatogonial were unaffected at doses below 6 Gy, higher doses reduced their number, indicating that stem cell killing also contributed to the failure of recovery. After 10 weeks, there was no further recovery and even a decline in spermatogonial differentiation in BN rats, but in SHR rats, sperm production returned to control levels by 20 weeks after 5.0 Gy and, after 7.5 Gy, differentiation resumed in 60% of tubules by 30 weeks. Suppression of testosterone and gonadotropins after irradiation restored production of differentiated cells in nearly all tubules in BN rats and in all tubules in SHR rats. Thus the differences in recovery of spermatogenesis between strains were a result of both quantitative differences in their sensitivities to a radiation-induced, hormone-dependent block of spermatogonial differentiation and qualitative interstrain differences in the progression of post-irradiation recovery. The progression of recovery in SHR rats was similar to the prolonged delays in recovery of human spermatogenesis after cytotoxic agent exposure and thus may be a system for investigating a phenomenon also observed in men.

The protective effect of regucalcin against radiation-induced damage in testicular cells

“…Moreover, RGN overexpression was associated with an increased number of viable sperm cells and lower incidence of morphological defects, concomitantly with lower sperm counts and motility [19]. The higher sperm viability and the diminished incidence of A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 5 morphological defects exhibited by the sperm of transgenic animals overexpressing (Tg-RGN) may be a consequence of the RGN ability to counteract oxidative stress, as recently showed by our research group [20,21]. On the other hand, the lower sperm motility in Tg-RGN was explained by the altered Ca 2+ -influx rates observed in the epididymal tissues of these animals [19].…”

“…These findings led us to hypothesize that RGN may have a role counteracting the damaging effects of radiation on testicular cells. The present work aims to evaluate the spermatogenic status and reproductive parameters of Tg-RGN comparatively with their wild-type (Wt) counterparts ten weeks after radiation treatment with a single dose of 6 Gy, which is known to cause a significant depletion of germ cells in rat testis [5,22].…”

“…The germinal epithelium is very sensitive to exogenous damaging factors [2] due to its high mitotic rate, and for this reason, cancer treatments frequently have several adverse effects on male fertility, which implicate permanent or transitory impairment of spermatogenesis [3]. Concerning radiotherapy, it is also known both in rodents and humans that the extent of testicular injury is directly related to the dose of radiation delivered [4,5].…”

Hyperthermia versus busulfan: Finding the effective method in animal model of azoospermia induction

“…By reviewing the literature, we can see that animal models of azoospermia are very applicable for the evaluation of new treatment methods. Different models have been described for azoospermia induction in animals including busulfan injection (Chen, Liang, & Wang, ), testicular heat stress (Durairajanayagam, Agarwal, & Ong, ), testicular torsion (Azizollahi et al, ), radiation (Abuelhija, Weng, Shetty, & Meistrich, ) and cryptorchidism induction (Absalan, Movahedin, & Mowla, ). Two prevalent methods to deplete germ cells from testes are busulfan injection and hyperthermia exposure (Chen et al, ; Durairajanayagam et al, ).…”

Cell‐specific ablation in the testis: what have we learned?

“…difficult to breed, immunocompatibility issues with donor cells, use of other species) (Zhang et al ., 2006). Even within mice, the removal of germ cells using busulfan is a strain‐dependent balance between the required toxicity to kill sufficient germ cells and the sensitivity of the animal to the wider toxicological effects of the drug, particularly on haematopoiesis (Meistrich et al ., 1978; Abuelhija et al ., 2013). In this context, radiation provides a useful alternative to busulfan; the fact that it has not been taken up widely probably reflects the general move of researchers away from use of radiation wherever possible and the ready availability and convenience of a single busulfan injection which requires significantly less specific training, infrastructure or administrative oversight.…”