Numerical Chromosomal Abnormalities in Rat Epididymal Spermatozoa Following Chronic Cyclophosphamide Exposure Export

@article{citeulike:1281989, abstract = {Chronic, low-dose treatment of male rats with cyclophosphamide, a chemotherapeutic agent, is known to affect progeny outcome adversely in a dose-dependent and time-specific manner, resulting in increased pre- and postimplantation loss as well as malformations. Concern exists regarding the genetic quality of mature gametes exposed to cyclophosphamide during mitosis and meiosis. The goal of the present study was to determine the effect of chronic cyclophosphamide treatment during spermatogenesis on the frequency of numerical chromosomal anomalies in epididymal spermatozoa. Male rats were treated with either saline or cyclophosphamide (6 mg kg-1 day-1) for 6 or 9 wk, and cauda epididymal spermatozoa were collected. The rat sperm Y-4 fluorescence in situ hybridization assay was used to assess the induction of spermatozoal disomy, nullisomy, and diploidy involving chromosomes Y and 4. The overall frequency of numerically abnormal spermatozoa was elevated approximately 2-fold (P < 0.001) after 9 wk of cyclophosphamide treatment. Exposure for 9 wk, but not for 6 wk, significantly increased the frequency of spermatozoa with chromosome 4 disomy (P < 0.02) and nullisomy (P < 0.05), but disomy Y and diploidy were not significantly increased with treatment compared to corresponding controls. Independent of treatment, only 27\% of aneuploid spermatozoa presented with morphological abnormalities, but all diploid spermatozoa were approximately twice the size of normal cells. Thus, cyclophosphamide disrupts meiotic events before pachynema during spermatogenesis, emphasizing the potential for adverse progeny outcomes following genotoxic damage. 10.1095/biolreprod.103.016261}, author = {Barton, Tara S. and Wyrobek, Andrew J. and Hill, Francesca S. and Robaire, Bernard and Hales, Barbara F.}, citeulike-article-id = {1281989}, citeulike-linkout-0 = {http://dx.doi.org/10.1095/biolreprod.103.016261}, citeulike-linkout-1 = {http://www.biolreprod.org/cgi/content/abstract/69/4/1150}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/12773405}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=12773405}, day = {1}, doi = {10.1095/biolreprod.103.016261}, journal = {Biol Reprod}, keywords = {chromosome, cyclophosphamide, disomy, epididymal\_spermatozoa, rat, spermatozoa}, month = {October}, number = {4}, pages = {1150--1157}, posted-at = {2007-05-07 16:13:26}, priority = {0}, title = {Numerical Chromosomal Abnormalities in Rat Epididymal Spermatozoa Following Chronic Cyclophosphamide Exposure}, url = {http://dx.doi.org/10.1095/biolreprod.103.016261}, volume = {69}, year = {2003} }

TY - JOUR ID - citeulike:1281989 L3 - citeulike-article-id:1281989 N2 - Chronic, low-dose treatment of male rats with cyclophosphamide, a chemotherapeutic agent, is known to affect progeny outcome adversely in a dose-dependent and time-specific manner, resulting in increased pre- and postimplantation loss as well as malformations. Concern exists regarding the genetic quality of mature gametes exposed to cyclophosphamide during mitosis and meiosis. The goal of the present study was to determine the effect of chronic cyclophosphamide treatment during spermatogenesis on the frequency of numerical chromosomal anomalies in epididymal spermatozoa. Male rats were treated with either saline or cyclophosphamide (6 mg kg-1 day-1) for 6 or 9 wk, and cauda epididymal spermatozoa were collected. The rat sperm Y-4 fluorescence in situ hybridization assay was used to assess the induction of spermatozoal disomy, nullisomy, and diploidy involving chromosomes Y and 4. The overall frequency of numerically abnormal spermatozoa was elevated approximately 2-fold (P < 0.001) after 9 wk of cyclophosphamide treatment. Exposure for 9 wk, but not for 6 wk, significantly increased the frequency of spermatozoa with chromosome 4 disomy (P < 0.02) and nullisomy (P < 0.05), but disomy Y and diploidy were not significantly increased with treatment compared to corresponding controls. Independent of treatment, only 27% of aneuploid spermatozoa presented with morphological abnormalities, but all diploid spermatozoa were approximately twice the size of normal cells. Thus, cyclophosphamide disrupts meiotic events before pachynema during spermatogenesis, emphasizing the potential for adverse progeny outcomes following genotoxic damage. 10.1095/biolreprod.103.016261 IS - 4 JF - Biol Reprod EP - 1157 TI - Numerical Chromosomal Abnormalities in Rat Epididymal Spermatozoa Following Chronic Cyclophosphamide Exposure VL - 69 SP - 1150 KW - chromosome KW - cyclophosphamide KW - disomy KW - epididymal_spermatozoa KW - rat KW - spermatozoa AU - Barton, Tara AU - Wyrobek, Andrew AU - Hill, Francesca AU - Robaire, Bernard AU - Hales, Barbara PY - 2003/10/01/ UR - http://dx.doi.org/10.1095/biolreprod.103.016261 ER -