应用小鼠模型评估PGD的风险
发布时间：2018-09-13 06:59
【摘要】： PGD(胚胎植入前基因诊断)技术可以为那些患有单基因疾病、染色体非整倍性以及X-染色体偶联的遗传性疾病的夫妇提供生育的机会。由于通过PGD技术孕育的第一个儿童目前才16岁，因此目前还无法判断PGD技术是否对这些后代的成年阶段具有远期的危害。为了阐明这个问题，我们与生殖生物学国家重点实验室合作，采用生命周期较短的小鼠作为动物模型，有利于研究成年的子代小鼠的生物行为以及在蛋白水平对重要脏器的功能进行评估，并利于发现二者之间的联系。从正常受孕的4细胞期胚胎中除去一个卵裂球，这些处理过的胚胎中一部分植入代孕母鼠的体内，另一部分继续体外培养至胚泡期以和未处理的对照胚胎组进行植入前胚胎发育情况的比较。在出生后的小鼠生长到成年阶段，观察其生物行为，然后通过蛋白质组学技术分析重要脏器的蛋白表达谱。在前期的合作研究中，生殖生物学国家重点实验室已经发现实验组和对照组之间，在植入前胚胎的发育效率方面没有显著差异，除了实验组小鼠体重增加之外其他的生物行为学方面没有显著差异。本研究在三组动物的重要脏器内我们一共发现了370个差异蛋白点。大量的差异蛋白富集于代谢通路以及线粒体调控通路中，我们推测这可能能够解释实验组小鼠体重增加的问题。结果提示，虽然PGD技术是能够有效地帮助不育夫妇的辅助生殖技术，，但是这项技术会影响重要脏器的蛋白表达谱，从而诱发体重的增加以及其他潜在的疾病。应该对PGD的安全性进行进一步的评估。
[Abstract]:PGD (preimplantation genetic diagnosis) technology can provide couples with single gene disease, chromosomal aneuploidy and X- chromosome coupling genetic diseases with reproductive opportunities. Since the first child conceived by PGD is now only 16 years old, it is not yet possible to determine whether PGD is a long-term hazard to the adult age of these offspring. To illustrate this problem, we worked with the State key Laboratory of Reproductive Biology, using mice with shorter life cycles as animal models. It is helpful to study the biological behavior of adult mice and evaluate the function of important organs at the protein level, and to find out the relationship between them. A cleavage ball is removed from 4-cell embryos normally conceived, and some of these processed embryos are implanted into the body of the surrogate. In the other part, the development of preimplantation embryos was compared between untreated and untreated embryos. The biological behavior of postnatal mice was observed and the protein expression profiles of important organs were analyzed by proteomics. In previous collaborative studies, the State key Laboratory of Reproductive Biology has found no significant difference in the developmental efficiency of preimplantation embryos between the experimental and control groups. There was no significant difference in biological behavior except weight gain in the experimental group. In this study, 370 differentially expressed proteins were found in important organs of three groups of animals. A large number of differentially expressed proteins are concentrated in metabolic pathways and mitochondrial regulatory pathways. We speculate that this may explain the problem of weight gain in experimental mice. The results suggest that although PGD is an effective assisted reproductive technique for infertile couples, it can affect the protein expression profile of important organs and induce weight gain and other underlying diseases. The security of PGD should be further evaluated.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R-332
本文编号：2240416
[Abstract]:PGD (preimplantation genetic diagnosis) technology can provide couples with single gene disease, chromosomal aneuploidy and X- chromosome coupling genetic diseases with reproductive opportunities. Since the first child conceived by PGD is now only 16 years old, it is not yet possible to determine whether PGD is a long-term hazard to the adult age of these offspring. To illustrate this problem, we worked with the State key Laboratory of Reproductive Biology, using mice with shorter life cycles as animal models. It is helpful to study the biological behavior of adult mice and evaluate the function of important organs at the protein level, and to find out the relationship between them. A cleavage ball is removed from 4-cell embryos normally conceived, and some of these processed embryos are implanted into the body of the surrogate. In the other part, the development of preimplantation embryos was compared between untreated and untreated embryos. The biological behavior of postnatal mice was observed and the protein expression profiles of important organs were analyzed by proteomics. In previous collaborative studies, the State key Laboratory of Reproductive Biology has found no significant difference in the developmental efficiency of preimplantation embryos between the experimental and control groups. There was no significant difference in biological behavior except weight gain in the experimental group. In this study, 370 differentially expressed proteins were found in important organs of three groups of animals. A large number of differentially expressed proteins are concentrated in metabolic pathways and mitochondrial regulatory pathways. We speculate that this may explain the problem of weight gain in experimental mice. The results suggest that although PGD is an effective assisted reproductive technique for infertile couples, it can affect the protein expression profile of important organs and induce weight gain and other underlying diseases. The security of PGD should be further evaluated.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R-332
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