【摘要】： PGD(胚胎植入前基因診斷)技術(shù)可以為那些患有單基因疾病、染色體非整倍性以及X-染色體偶聯(lián)的遺傳性疾病的夫婦提供生育的機(jī)會(huì)。由于通過(guò)PGD技術(shù)孕育的第一個(gè)兒童目前才16歲，因此目前還無(wú)法判斷PGD技術(shù)是否對(duì)這些后代的成年階段具有遠(yuǎn)期的危害。為了闡明這個(gè)問(wèn)題，我們與生殖生物學(xué)國(guó)家重點(diǎn)實(shí)驗(yàn)室合作，采用生命周期較短的小鼠作為動(dòng)物模型，有利于研究成年的子代小鼠的生物行為以及在蛋白水平對(duì)重要臟器的功能進(jìn)行評(píng)估，并利于發(fā)現(xiàn)二者之間的聯(lián)系。從正常受孕的4細(xì)胞期胚胎中除去一個(gè)卵裂球，這些處理過(guò)的胚胎中一部分植入代孕母鼠的體內(nèi)，另一部分繼續(xù)體外培養(yǎng)至胚泡期以和未處理的對(duì)照胚胎組進(jìn)行植入前胚胎發(fā)育情況的比較。在出生后的小鼠生長(zhǎng)到成年階段，觀察其生物行為，然后通過(guò)蛋白質(zhì)組學(xué)技術(shù)分析重要臟器的蛋白表達(dá)譜。在前期的合作研究中，生殖生物學(xué)國(guó)家重點(diǎn)實(shí)驗(yàn)室已經(jīng)發(fā)現(xiàn)實(shí)驗(yàn)組和對(duì)照組之間，在植入前胚胎的發(fā)育效率方面沒(méi)有顯著差異，除了實(shí)驗(yàn)組小鼠體重增加之外其他的生物行為學(xué)方面沒(méi)有顯著差異。本研究在三組動(dòng)物的重要臟器內(nèi)我們一共發(fā)現(xiàn)了370個(gè)差異蛋白點(diǎn)。大量的差異蛋白富集于代謝通路以及線粒體調(diào)控通路中，我們推測(cè)這可能能夠解釋實(shí)驗(yàn)組小鼠體重增加的問(wèn)題。結(jié)果提示，雖然PGD技術(shù)是能夠有效地幫助不育夫婦的輔助生殖技術(shù)，，但是這項(xiàng)技術(shù)會(huì)影響重要臟器的蛋白表達(dá)譜，從而誘發(fā)體重的增加以及其他潛在的疾病。應(yīng)該對(duì)PGD的安全性進(jìn)行進(jìn)一步的評(píng)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.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2007
【分類號(hào)】：R-332

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