Vanadate, an inhibitor of tyrosine phosphatases, induced premature anaphase in oocytes and aneuploidy and polyploidy in mouse bone marrow cells.
Protein tyrosine phosphatases are needed for activating maturation promoting factor, meiotic spindle assembly and spindle checkpoint inactivation. The protein phosphatase inhibitor vanadate was used to upset the kinase-phosphatase equilibrium during oocyte maturation (OM) and the metaphase anaphase transition (MAT) prior to cytogenetic analyses of mouse oocytes and bone marrow cells. ICR females received pregnant mare serum gonadotrophin (PMSG) and 48h later received human chorionic gonadotrophin (hCG). Vanadate doses of 0, 5, 15, and 25mg/kg were administered intraperitoneally immediately after hCG and ovulated oocytes and bone marrow cells were processed for cytogenetic analyses 18h after hCG. Data were analyzed by Chi-square and Fisher's exact tests. Vanadate induced different cytogenetic abnormalities in oocytes and in bone marrow cells. The frequencies of oocytes exhibiting premature anaphase (spontaneous activation) in vanadate exposed mice were significantly (P<0.01) elevated over controls; whereas, in bone marrow cells, the levels of tetraploidy, hyperploidy and premature centromere separation were significantly (P<0.01) increased by vanadate treatment. These results suggest that alteration of the kinase-phosphatase equilibrium during OM and the MAT leads to cytogenetic abnormalities that differ between oocytes and bone marrow cells.
Mailhes
John B
JB
Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. jmailh@lsuhsc.edu
Hilliard
Colette
C
Fuseler
John W
JW
London
Steve N
SN
D000705:Anaphase / Q000187:drug effects*; D024422:Aneugens / Q000633:toxicity*; D000782:Aneuploidy; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects*; D002869:Chromosome Aberrations / Q000139:chemically induced*; D020732:Cytogenetic Analysis; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D016296:Mutagenesis; D009865:Oocytes / Q000187:drug effects*; D011123:Polyploidy; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D014638:Vanadates / Q000633:toxicity*
D024422:Aneugens; D004791:Enzyme Inhibitors; D014638:Vanadates; D017027:Protein Tyrosine Phosphatases