Contribution of chromosomal imbalance to sperm selection and pre-implantation loss in translocation-heterozygous Chinese hamsters

Abstract

Chinese hamster stocks with various structurally abnormal chromosomes have been produced by X irradiation. Among these stocks, 18 with various reciprocal translocations were used to investigate the participation of unbalanced gametes in fertilization and the development of unbalanced embryos. Among males as well as females heterozygous for the same translocation, there is no difference in the frequency of each disjunctional class. The participation of chromosomally unbalanced gametes in fertilization was investigated by chromosomal analysis of meiotic cells in heterozygotes for the 18 reciprocal translocations and pronuclei of fertilized ova obtained from crossing these heterozygotes. Compared with the expected frequencies from MII scoring, the frequencies of male pronuclei having a common deficiency of chromosome 1 (1q17→1q42) or chromosome 3 (3p23→3q31) decreased significantly in one-cell embryos. 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 abnormalities as those decreased in male pronuclei from the translocation heterozygotes were all consistent with those estimated from MII scoring. These results revealed clearly that most gametes with nullisomies as well as disomies for any chromosomal segments may participate in fertilization, whereas only male gametes nullisomic for certain segments of chromosomes 1 and 3 failed to participate in fertilization. The zygotic selection of chromosomal imbalance was also investigated by direct chromosomal and morphological analyses of preimplantation embryos from crosses between karyotypically normal females and male heterozygotes from the 18 stocks with various reciprocal translocations. These analyses revealed that some embryos were arrested in development at the two-cell stage. The karyotype of these two-cell embryos had a common deficiency in a segment of chromosome 1 or chromosome 2. Embryos with partial monosomy including chromosomes 1, 3, 4 and 5 showed arrested development at four- to eight-cell stages. Among day 4 embryos, some chromosomally unbalanced embryos, mainly with a deficiency of segments of chromosomes 1p, 1q, 2q, 5q, 7q and 8, had fewer blastomeres than karyotypically normal and balanced embryos. The homology between Chinese hamster and mouse chromosomes relating to abnormal embryogenesis at early stages has been partially confirmed from reported maps of chromosomes. The Chinese hamster is useful for further cytogenetic studies during the stages of meiosis and early embryogenesis.

Mechanisms and consequences of paternally‐transmitted chromosomal abnormalities

“…However, it remains possible that aneuploidy for other chromosomes and other types of chromosomal abnormalities may affect sperm maturation and fertilizing capacity. Indeed, results obtained with translocation carriers in Chinese hamsters suggested that sperm carrying specific chromosomal imbalances failed to participate in fertilization (Sonta et al, 1991; Sonta, 2004).…”

Chromosomal abnormalities in patients with infertility

“…Chromosomal abnormalities may lead not only to meiotic disturbances and gameto genic disruption, but also to the production of chromo somally unbalanced gametes. Normally, gametes with chromosomal abnormalities have reduced reproductive potential, since the natural selection reduces the proba bility of fertilization, embryonic cell division and implantation of embryos with some types of chromo somal abnormalities [8][9][10]. ART utilization, espe cially intracytoplasmic sperm injection, bypasses this natural barrier to fertilization, increasing the risk of 1 The article was translated by the authors.…”