SUSCEPTIBILITY TO VINBLASTINE-INDUCED ANEUPLOIDY AND PREFERENTIAL CHROMOSOME SEGREGATION DURING MEIOSIS-I IN ROBERTSONIAN HETEROZYGOUS MICE

Chromosome segregation at meiosis I was studied in oocytes and spermat ocytes of four different Robertsonian (Rb) heterozygous mouse stocks b y cytogenetic analysis of meiotic products. Two Rb heterozygotes spont aneously yielded high frequencies of unbalanced oocytes. In one case, Rb(2.18)Rma, the excess hyperploidy was mainly accounted for by nondis junction of normal bivalents, suggesting a generalized impairment of m eiotic segregation. In each stock, frequencies of hyperploid spermatoc ytes were either not significantly different or significantly lower th an the corresponding frequencies in the oocytes. This confirmed the gr eater risk of segregational errors in female than in male carriers of the same Rb metacentric. The hypothesis that an error prone system of meiotic segregation, such as the trivalent configuration of single Rb heterozygous oocytes, could be hypersensitive to chemically induced ma lsegregation was tested by injecting Rb heterozygous females with low doses of vinblastine (VBL). An intraperitoneal injection of 0.06 or 0. 09 mg/kg VBL before the first meiotic division significantly increased the spontaneous frequency of hyperploid oocytes, inducing segregation al errors of both the trivalent and normal bivalents. The comparison o f these data with VBL effects in B6C3F1 mice showed that single Rb het erozygous oocytes are more sensitive to VBL-induced meiotic aneuploidy than oocytes with a standard karyotype. Although segregation distorti on has been repeatedly shown in the progeny of Rb heterozygous mice wi th a significant excess of all telocentric balanced offspring, it has never been demonstrated whether this is a primary event occurring duri ng meiotic segregation or a consequence of selective postconceptional death. In this study, we showed that preferential segregation occurred during female meiosis in all the Rb stocks tested. When segregation d istortion was analyzed separately in balanced unbalanced oocytes, the latter did not show preferential segregation, suggesting that, when th e two telocentrics segregated from each other, then the metacentric wa s randomly directed to the ovum or the polar body. (C) 1996 Wiley-Liss , Inc.