Effects of multiple doses of cyclophosphamide on mouse testes: Accessing the germ cells lost, and the functional damage of stem cells

Abstract

Spermatogenesis is sensitive to the chemotherapeutic drug cyclophosphamide, which decreases the patients’ sperm count. Since the recovery of fertility is dependent on regeneration from stem cells, in the present study we evaluated the ability of cyclophosphamide-exposed stem spermatogonia from mice to regenerate spermatogenesis in situ and after transplantation. When seven doses of cyclophosphamide were given at 4-day intervals, the differentiating germ cells were largely eliminated but ~50% of the undifferentiated type A spermatogonia remained. We monitored the recovery and found that sperm production recovered to 64% of control within the time expected. When the cyclophosphamide-surviving spermatogonia were transplanted into recipient mice, recovery of spermatogenesis from the cyclophosphamide-exposed donor cells was observed, but was reduced when compared to cells from cryptorchid donors. Thus, multidose regimens of cyclophosphamide did not eliminate the stem spermatogonia, but resulted in cell loss and residual damage.

Interventional effects of squid ink polysaccharides on cyclophosphamide-associated testicular damage in mice

“…Testis weight is connected with quantities of different differentiational spermatids (19). We found results here that were consistent with those in our previous work which indicated that CP exposure resulted in decreases in sperm count and survival ratio, an increased sperm abnormality ratio, as well as signifi cant reductions in body weight, testis weight and index in CP-treated mice, which also agreed with current data (3,4,9,20).…”

“…Data in model mice indicated that the interval needed for the recovery of fertility was directly related to the killing level of the spermatogonial stem cells, and that chemical agents could injury the somatic tissue, even though numerous spermatogonia survived the cytotoxic treatment in rat testes, recovery of the seminiferous epithelium was still impossible (4). From the aforementioned information, it is found that CP-induced damage to the male reproductive system is both inevitable and severe, and that reduction of the therapeutic effect of this chemotherapeutic drug on male tumour patients originates from clinical inadequate dosing of the drug due to its chemical toxicity.…”

Leydig cells contribute to the inhibition of spermatogonial differentiation after irradiation of the rat

“…Since EDS is a strong bifunctional alkylating agent, we tested this possibility by treating irradiated rats with another strong bifunctional alkylating agent, cyclophosphamide (CP), which is known to act on spermatogonia (Cai et al , 1997; Drumond et al , 2011). CP did not appear to kill LCs (Supplemental Fig.…”

Cadherin and vimentin immunoexpression in the testis of normal and induced infertility models of albino rats

“…It was chosen in the current study as it was previously shown to provide a suitable model for observing processes occurring in the seminiferous epithelium during impairment and restoration of spermatogenesis. It is also commonly used to examine degenerative changes in the seminiferous epithelium and spermatogonial stem cell function [9].…”