Taxol-induced meiotic maturation delay, spindle defects, and aneuploidy in mouse oocytes and zygotes.
To increase our understanding about the potential risks of chemically-induced aneuploidy, more information about the various mechanisms of aneuploidy induction is needed, particularly in germ cells. Most chemicals that induce aneuploidy inhibit microtubule polymerization. However, taxol alters microtubule dynamics by enhancing polymerization and stabilizing the polymer fraction. We tested the hypothesis that taxol induces meiotic delay, spindle defects, and aneuploidy in mouse oocytes and zygotes. Super-ovulated ICR mice received 0 (control), 2.5, 5.0, and 7.5 mg/kg taxol intraperitoneally immediately after HCG. Females were paired (1:1) with males for 17 h after taxol treatment. Mated females were given colchicine 25 h after taxol and their one-cell zygotes were collected 16 h later. Ovulated oocytes from non-mated females were collected 17 h after taxol. Chromosomes were C-banded for cytogenetic analyses. Oocytes were also collected from another group of similarly treated females for in situ chromatin and microtubule analyses. Taxol significantly (p<0.01) enhanced the proportion of oocytes exhibiting parthenogenetic activation, chromosomes displaced from the meiotic spindle, and sister-chromatid separation. Moreover, 7.5 mg/kg taxol significantly (p<0.01) increased the proportions of metaphase I and diploid oocytes and polyploid zygotes. A significant (p<0.01) dose response for taxol-induced hyperploidy in oocytes and zygotes was found. These results support the hypothesis that taxol-induced meiotic delay and spindle defects contribute to aneuploid mouse oocytes and zygotes.
Department of Obstetrics and Gynecology, Louisiana State University Medical Center, P.O. Box 33932, Shreveport LA 71130, USA. jmailh@lsumc.edu
J B
JB
Mailhes
M J
MJ
Carabatsos
D
D
Young
S N
SN
London
M
M
Bell
D F
DF
Albertini
D000782:Aneuploidy; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D005260:Female; D008540:Meiosis / Q000187:drug effects* / Q000235:genetics; D008677:Metaphase / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D008870:Microtubules / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D008941:Spindle Apparatus / Q000187:drug effects* / Q000235:genetics / Q000473:pathology; D015053:Zygote / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D002843:Chromatin; D017239:Paclitaxel