Transmission of chromosomal abnormalities: participation of chromosomally unbalanced gametes in fertilization and early development of unbalanced embryos in the Chinese hamster

Abstract

Using 14 Chinese hamster stocks with various reciprocal translocations, chromosomally unbalanced gametes were produced and used to investigate the participation of the unbalanced gametes in fertilization and the development of unbalanced embryos. The selection of chromosomally abnormal gametes during fertilization was investigated by the chromosomal analysis of meiotic cells in heterozygotes for the 14 reciprocal translocations and pronuclei of fertilized ova obtained from crossing these heterozygotes. Compared with the expected frequencies from meiotic metaphase II (MII) scoring, the frequencies of male pronuclei having commonly a deficiency of chromosome 1 (q14→q42) or chromosome 3 (p23→q31) in one-cell embryos decreased significantly. However, the frequencies of male pronuclei with other abnormalities were all consistent with those expected from MII scoring. In contrast, the frequencies of female pronuclei with any karyotype including the same ones, as those decreased in male pronuclei from the translocation heterozygotes were all consistent with those estimated from MII scoring. These results suggest that gametes with nullisomies as well as disomies for any chromosomal segments may mostly participate in fertilization, whereas some sperm nullisomic for the specific segments of chromosomes 1 and 3 may fail to fertilize. On the other hand, the zygotic selection of chromosomal imbalance was investigated by direct analyses of pre-implantation embryos from crosses between chromosomally normal females and male heterozygotes from the 14 stocks with various reciprocal translocations. The chromosomal and morphological analysis revealed that some embryos were arrested in development at the two-cell stage and their common abnormality was partial monosomy for chromosome 1 or 2. Embryos with partial monosomy including chromosomes 1, 3 and 4 showed arrested development at four–eight-cell stages. Among day 4 embryos, some chromosomally unbalanced embryos, mainly with a deficiency of other segments, such as chromosomes 1p, 2q, 5q and 8, had fewer blastomeres than karyotypically normal and balanced embryos. The homology between the mouse and the Chinese hamster chromosomes relating to the developmental abnormalities at early stages was partially confirmed.