日前,,中科院動物所周琪研究員領(lǐng)導(dǎo)的生殖工程研究組與南京醫(yī)科大學(xué)沙家豪教授實驗室合作,研究利用小鼠作為動物模型,按照人PGD胚胎活檢操作流程構(gòu)建了PGD活檢小鼠模型,并且對胚胎早期發(fā)育、植入率及出生情況進行了研究,。通過對子代的生理表型進行長期觀察,發(fā)現(xiàn)這些小鼠在體重指標上與對照組小鼠存在差異,,更重要的是在針對小鼠學(xué)習(xí)和記憶力的行為學(xué)檢測中,,PGD活檢小鼠模型與對照組相比存在顯著差異,。針對這種表型,采用蛋白質(zhì)組學(xué)的方法,,對小鼠腦部蛋白質(zhì)表達進行了分析,。在全部差異蛋白中,約50%蛋白與神經(jīng)退行性疾病的發(fā)生具有密切的關(guān)聯(lián),?;顧z組小鼠的脫髓鞘病理表型明顯增加,在髓鞘切面面積及密度上都與對照組有顯著差異,。因此,,研究提示活檢技術(shù)有可能誘發(fā)子代小鼠的神經(jīng)退行性疾病發(fā)生,有必要增加對輔助生殖技術(shù)中相關(guān)環(huán)節(jié)的基礎(chǔ)研究,,建立規(guī)范的操作體系,,從而將這種風(fēng)險降低到最小。
據(jù)悉,,第三代輔助生殖技術(shù)在1990年獲得成功,。這項技術(shù)主要針對家族遺傳病史的人群及高齡產(chǎn)婦,在其胚胎發(fā)育早期利用胚胎活檢技術(shù)去除一個卵裂球,,經(jīng)分子生物學(xué)檢測后,,正常的胚胎將被移入婦女子宮,而異常的胚胎將被棄掉,,因此這種技術(shù)稱之為植入前遺傳診斷(Preimplantation Genetic Diagnosis,,PGD)技術(shù)。這項技術(shù)的重要意義在于已經(jīng)不單單是針對治療那些不孕不育人群,,而是通過這項技術(shù)可以提高整體的人口出生質(zhì)量,,提高人口素質(zhì)。但是針對這項技術(shù)開展的基礎(chǔ)研究還比較薄弱,,特別是針對該技術(shù)在子代長期發(fā)育中是否存在潛在的風(fēng)險還沒有被闡述,。(生物谷Bioon.com)
生物谷推薦原始出處:
Mol Cell Proteomics. 2009 Mar 11
Evaluation of blastomere biopsy using mouse model indicates the potential high-risk of neurodegenerative disorders in the offspring.
Yu Y, Wu J, Fan Y, Lv Z, Guo X, Zhao C, Zhou R, Zhang Z, Wang F, Xiao M, Chen L, Zhu H, Chen W, Lin M, Liu J, Zhou Z, Wang L, Huo R, Zhou Q, Sha J.
Preimplantation genetic diagnosis (PGD), used in clinical practice, is offered to couples that may suffer from a monogenetic disorder, chromosome aneuploidy or X-linked disease. However, blastomere biopsy, as an indispensable manipulation during the PGD procedure has not been assessed for its long-term health implications. Using a mouse model, we have investigated the effect of blastomere biopsy of in vitro cultured 4-cell embryos on preimplantation development efficiency, postnatal growth, physiological and behavioral activity compared with control, non-biopsied embryos. The mice generated after blastomere biopsy showed weight increase and some memory decline compared with the control group. Further, protein expression profiles in adult brains were analyzed by a proteomics approach. A total of 36 proteins were indentified with significant differences between the biopsied and control groups, and the alterations in expression of most of these proteins have been associated with neurodegenerative diseases. Furthermore, hypomyelination of the nerve fibers was evidently observed in the brains of mice in the biopsied group. This study suggested that the nervous system may be sensitive to blastomere biopsy procedures and indicated an increased relative risk of neurodegenerative disorders in the offspring generated following blastomere biopsy. Thus, more studies should be performed to address the possible adverse effects of blastomere biopsy on the development of offspring and the overall safety of PGD technology should be more rigorously assessed.