Marchetti Francesco, Bishop Jack B, Cosentino Lidia, Moore Dan, Wyrobek Andrew J
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, California 94550, USA.
Biol Reprod. 2004 Mar;70(3):616-24. doi: 10.1095/biolreprod.103.023044. Epub 2003 Oct 29.
The developmental consequences of chromosomal aberrations in embryos include spontaneous abortions, morphological defects, inborn abnormalities, and genetic/chromosomal diseases. Six germ-cell mutagens with different modes of action and spermatogenic stage sensitivities were used to investigate the relationship between the types of cytogenetic damage in zygotes with their subsequent risk of postimplantation death and of birth as a translocation carrier. Independent of the mutagen used, over 98% of paternally transmitted aberrations were chromosome type, rather than chromatid type, indicating that they were formed during the period between exposure of male germ cells and initiation of the first S phase after fertilization. There were consistent one-to-one agreements between the proportions of a) zygotes with unstable aberrations and the frequencies of dead embryos after implantation (slope = 0.87, confidence interval [CI]: 0.74, 1.16) and b) zygotes with reciprocal translocations and the frequency of translocation carriers at birth (slope = 0.74, CI: 0.48, 2.11). These findings suggest that chromosomal aberrations in zygotes are highly predictive of subsequent abnormal embryonic development and that development appears to proceed to implantation regardless of the presence of chromosomal abnormalities. Our findings support the hypothesis that, for paternally transmitted chromosomal aberrations, the fate of the embryo is already set by the end of G1 of the first cell cycle of development.
胚胎中染色体畸变的发育后果包括自然流产、形态缺陷、先天性异常以及遗传/染色体疾病。使用六种具有不同作用方式和生精阶段敏感性的生殖细胞诱变剂，来研究合子中细胞遗传学损伤类型与其随后的着床后死亡风险以及作为易位携带者出生风险之间的关系。无论使用何种诱变剂，超过98%的父系传递的畸变是染色体型而非染色单体型，这表明它们是在雄性生殖细胞暴露后至受精后第一个S期开始之间形成的。在以下两者的比例之间存在一致的一一对应关系：a）具有不稳定畸变的合子与着床后死亡胚胎的频率（斜率 = 0.87，置信区间[CI]：0.74，1.16），以及b）具有相互易位的合子与出生时易位携带者的频率（斜率 = 0.74，CI：0.48，2.11）。这些发现表明，合子中的染色体畸变对随后的胚胎异常发育具有高度预测性，并且无论是否存在染色体异常，发育似乎都会进行到着床阶段。我们的发现支持这样的假设，即对于父系传递的染色体畸变，胚胎的命运在发育的第一个细胞周期的G1期末就已确定。
