title: 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.
authors: Department of Experimental Radiation Oncology, M.D. Anderson Cancer Center, University of Texas, 1515 Holcombe Blvd, Houston, TX 77030, USA.
authors: Ana Luiza
authors: AL
authors: Drumond
authors: Connie C
authors: CC
authors: Weng
authors: Gensheng
authors: G
authors: Wang
authors: Helio
authors: H
authors: Chiarini-Garcia
authors: Leticia
authors: L
authors: Eras-Garcia
authors: Marvin L
authors: ML
authors: Meistrich
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D017209:Apoptosis; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage*; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012670:Seminiferous Epithelium / Q000166:cytology; D013076:Sperm Count; D013091:Spermatogenesis / Q000187:drug effects*; D013093:Spermatogonia / Q000166:cytology / Q000187:drug effects* / Q000637:transplantation; D013737:Testis / Q000166:cytology / Q000187:drug effects*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide