DNA Microarray Reveals That High Proportions of Human Blastocysts from Women of Advanced Maternal Age Are Aneuploid and Mosaic
DNA Microarray Reveals That High Proportions of Human Blastocysts from Women of Advanced Maternal Age Are Aneuploid and Mosaic
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DOI：
10.1095/biolreprod.112.103192
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发表时间：
2012-12-01
影响因子：
3.6
通讯作者：
Gill, Jimmy
中科院分区：
文献类型：
--
作者：
Liu, Jianqiao;Wang, Weihua;Gill, Jimmy
滋养外胚层组织活检和基因芯片技术已成为人类植入前遗传学诊断的新技术。在这项研究中，我们全面检查了非整倍体形成的人胚泡体外生产的芯片和研究的临床结果后，移植的整倍体胚胎。将TE和内细胞团（ICM）的活检细胞进行微阵列处理，以检查23对染色体中的错误以及TE和ICM之间的一致性。结果发现，56.6%的囊胚为非整倍体。进一步分析表明，62.3%的非整倍体囊胚具有单个染色体异常，37.7%具有多个染色体异常。染色体错误可发生在任何染色体上，但在23对染色体中，21号染色体的错误最多（11.3%）。移植阵列筛选的囊胚产生高妊娠率（70.2%）和植入率（63.5%）。同一囊胚中TE和ICM细胞的微阵列显示，高比例的非整倍体囊胚（69.2%）为嵌合体，包括非整倍体TE和整倍体ICM，ICM和TE之间的不一致异常，或整倍体TE细胞和非整倍体ICM在同一囊胚中。这些结果表明，高比例的人囊胚体外生产的妇女的高龄产妇是非整倍体和镶嵌。人类胚泡中的23对染色体中的任何一对都可能发生错误。如果胚胎为非整倍体，则囊胚TE活检不能准确预测ICM中的染色体信息。嵌合体囊胚中存在整倍体ICM，这可能是人类植入前胚胎重要的分化机制。
Trophectoderm (TE) biopsy and DNA microarray have become the new technologies for preimplantation genetic diagnosis in humans. In this study, we comprehensively examined aneuploid formation in human blastocysts produced in vitro with microarray and investigated the clinical outcome after transfer of euploid embryos. Biopsied cells from either TE or inner cell mass (ICM) were processed for microarray to examine the errors in 23 pairs of chromosomes and the consistency between TE and ICM. It was found that 56.6% of blastocysts were aneuploid. Further analysis indicated that 62.3% of aneuploid blastocysts had single and 37.7% had multiple chromosomal abnormalities. Chromosome errors could occur in any chromosome, but errors in chromosome 21 accounted for the most (11.3%) among the 23 pairs of chromosomes. Transfer of array-screened blastocysts produced high pregnancy (70.2%) and implantation (63.5%) rates. Microarray of TE and ICM cells in the same blastocysts revealed that high proportions of aneuploid blastocysts (69.2%) were mosaic, including aneuploid TE and euploid ICM, inconsistent anomalies between ICM and TE, or euploid TE cells and aneuploid ICM in the same blastocyst. These results indicate that high proportions of human blastocysts produced in vitro from women of advanced maternal age are aneuploid and mosaic. Errors can occur in any of the 23 pairs of chromosomes in human blastocysts. Biopsy from TE in blastocysts does not exactly predict the chromosomal information in ICM if the embryos are aneuploid. Some mosaic blastocysts have euploid ICM, which may indicate important differentiate mechanism(s) of human preimplantation embryos.