Mammalian in vivo assays for aneuploidy in female germ cells

Mailhes, John B.; Preston, R. Julian; Lavappa, K. S.

doi:10.1016/0165-1110(86)90014-x

Cited by 37 publications

(5 citation statements)

References 45 publications

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“…The present results indicate that MBC is also capable of inducing embryonic aneuploidy during fertilization (meiosis 11). Previous reports have suggested that chemically induced meiotic delay may be associated with aneuploidy in mammalian germ cells (Mailhes et al, 1986(Mailhes et al, ,1993Miller and Adler, 1989;Mailhes and Aardema, 1992). The present results support this suggestion ( Fig.…”

Section: Discussionsupporting

confidence: 92%

Carbendazim (MBC) disrupts oocyte spindle function and induces aneuploidy in hamsters exposed during fertilization (meiosis II)

Zuelke

Perreault

1995

Molecular Reproduction Devel

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Peri-fertilization exposure to Carbendazim (MBC; a microtubule poison) induces infertility and early pregnancy loss in hamsters. Presently, both in vivo and in vitro techniques were employed to characterize the effects of MBC on cellular aspects of fertilization in hamsters. Exposure to MBC during either in vivo or in vitro fertilization (IVF) induced identical morphological abnormalities in the maternal chromatin of zygotes and embryos. These abnormalities included either multiple second polar bodies (PB2), and/or multiple small female pronuclei (PN), or meiotic arrest. Multiple PB2, multiple female PN, multiple PB2 with multiple female PN, or meiotic arrest were exhibited by approximately 31%, 15%, 12%, and 2% of the in vivo zygotes; and 3%, 16%, 36%, and 20% of IVF zygotes, respectively. The effects of MBC persisted to day 2 of pregnancy as indicated by decreased (P < 0.05) embryo development to the two-cell stage and the presence of micronuclei in 6% of two-cell embryos from MBC-treated females. Immunofluorescence analysis of microtubules (MTs) confirmed that MBC disrupted spindle MTs during IVF. Numerical chromosome analysis revealed that a single dose of MBC administered during in vivo fertilization induced aneuploidy in the resulting pronuclear-stage zygotes. The present data point to two mechanisms by which peri-fertilization MBC exposure may induce early pregnancy loss: 1) arrested meiosis with no zygotic cleavage; or 2) induction of zygotic aneuploidy with subsequent developmental arrest.

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Section: Discussionsupporting

confidence: 92%

Carbendazim (MBC) disrupts oocyte spindle function and induces aneuploidy in hamsters exposed during fertilization (meiosis II)

Zuelke

Perreault

1995

Molecular Reproduction Devel

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“…In this way, COL inhibits tubulin polymerization. It induces aneuploidy in female germ cells (Mailhes et al, 1986) and an increase in hyperploid spermatocytes and male meiotic delay (Adler, 1993;Leopardi, 1993). Several publications report its potential to induce aneuploidy/polyploidy in somatic mammalian cells of different species (reviewed by Galloway and Ivett, 1986) and in rodent cells in particular (Jenssen and Ramel, 1980;Tsuchimoto, 1980;Yamatoto and Kikuchi, 1981).…”

Section: Introductionmentioning

confidence: 99%

The in vivo gut micronucleus test detects clastogens and aneugens given by gavage

2001

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A general testing battery for pharmaceuticals includes a bacterial gene mutation assay, an in vitro chromosomal aberration or a gene mutation test on mammalian cells and an in vivo test for chromosome/genome mutations. The aim of this study was to determine whether the in vivo mouse gut micronucleus assay could be a more sensitive method to detect direct clastogens and/or aneugens given orally by gavage than the in vivo bone marrow micronucleus assay (which can also detect indirect genotoxins). Two laboratories collaborated in this project, one analysing bone marrow cells and the other analysing gut cells from the same animals. The reference substances tested in this study were colchicine (COL), carbendazim (CAR), tubulazole (TUB) and griseofulvin (GRI), all known aneugens, and 1,2-dimethylhydrazine (DMH), a colon carcinogen with clastogenic activity. For all substances tested, the in vivo gut micronucleus test was as sensitive as or more sensitive than the in vivo bone marrow micronucleus assay: COL and TUB induced micronuclei in both gut and bone marrow cells; DMH, CAR and GRI induced micronuclei only in gut cells. The results show that the micronucleus test on gut cells is able to detect clastogens and aneugens given orally by gavage, some of which were not detected by the bone marrow micronucleus test.

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“…In all studies, slides were analyzed for numerical chromosome changes according to the recommendations of the Aneuploidy Methodology and Test Data Review Committees for female and male germ cells [26,27]. Namely, hypoploid and hyperploid cells were scored separately.…”

Section: Methodsmentioning

confidence: 99%

Susceptibility to vinblastine‐induced aneuploidy and preferential chromosome segregation during meiosis I in Robertsonian heterozygous mice

Pacchierotti

Tiveron

Mailhes

et al. 1995

Teratog Carcinog Mutagen

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Chromosome segregation at meiosis I was studied in oocytes and spermatocytes of four different Robertsonian (Rb) heterozygous mouse stocks by cytogenetic analysis of meiotic products. Two Rb heterozygotes spontaneously yielded high frequencies of unbalanced oocytes. In one case, Rb(2.18)Rma, the excess hyperploidy was mainly accounted for by nondisjunction of normal bivalents, suggesting a generalized impairment of meiotic segregation. In each stock, frequencies of hyperploid spermatocytes were either not significantly different or significantly lower than the corresponding frequencies in the oocytes. This confirmed the greater 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 malsegregation 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 segregational errors of both the trivalent and normal bivalents. The comparison of these data with VBL effects in B6C3F1 mice showed that single Rb heterozygous oocytes are more sensitive to VBL-induced meiotic aneuploidy than oocytes with a standard karyotype. Although segregation distortion has been repeatedly shown in the progeny of Rb heterozygous mice with a significant excess of all telocentric balanced offspring, it has never been demonstrated whether this is a primary event occurring during 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 distortion was analyzed separately in balanced and unbalanced oocytes, the latter did not show preferential segregation, suggesting that, when the two telocentrics segregated from each other, then the metacentric was randomly directed to the ovum or the polar body.

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Mammalian in vivo assays for aneuploidy in female germ cells

Cited by 37 publications

References 45 publications

Carbendazim (MBC) disrupts oocyte spindle function and induces aneuploidy in hamsters exposed during fertilization (meiosis II)

Carbendazim (MBC) disrupts oocyte spindle function and induces aneuploidy in hamsters exposed during fertilization (meiosis II)

The in vivo gut micronucleus test detects clastogens and aneugens given by gavage

Susceptibility to vinblastine‐induced aneuploidy and preferential chromosome segregation during meiosis I in Robertsonian heterozygous mice

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