Etoposide induces chromosomal abnormalities in mouse spermatocytes and stem cell spermatogonia.
BACKGROUND
Etoposide (ET) is a chemotherapeutic agent widely used in the treatment of leukaemia, lymphomas and many solid tumours such as testicular and ovarian cancers, all of which are common in patients of reproductive age. The purpose of the study was to characterize the long-term effects of ET on male germ cells using sperm fluorescence in situ hybridization (FISH) analyses.


METHODS
Chromosomal aberrations (partial duplications and deletions) and whole chromosomal aneuploidies were detected in sperm of mice treated with a clinical dose of ET. Semen samples were collected at 25 and 49 days after dosing to investigate the effects of ET on meiotic pachytene cells and spermatogonial stem-cells, respectively.


RESULTS
ET treatment resulted in major increases in the frequencies of sperm-carrying chromosomal aberrations in both meiotic pachytene (27- to 578-fold) and spermatogonial stem-cells (8- to 16-fold), but aneuploid sperm were induced only after treatment of meiotic cells (27-fold) with no persistent effects in stem cells.


CONCLUSIONS
These results show that ET may have long-lasting effects on the frequencies of sperm with structural aberrations. This has important implications for cancer patients undergoing chemotherapy with ET because they may remain at higher risk for abnormal reproductive outcomes long after the end of chemotherapy.
Marchetti
Francesco
F
Biosciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA. marchetti2@llnl.gov
Pearson
Francesca S
FS
Bishop
Jack B
JB
Wyrobek
Andrew J
AJ
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D002869:Chromosome Aberrations / Q000139:chemically induced*; D005047:Etoposide / Q000633:toxicity*; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008540:Meiosis; D051379:Mice; D013090:Spermatocytes / Q000187:drug effects*; D013093:Spermatogonia / Q000187:drug effects*; D013234:Stem Cells / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide