Effect on embryos of injection of phosphorothioate-modified oligonucleotides into pregnant mice.
Effect on embryos of injection of phosphorothioate-modified oligonucleotides into pregnant mice.
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向怀孕小鼠注射硫代磷酸修饰的寡核苷酸对胚胎的影响。
DOI：
10.1089/ard.1993.3.391
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Crain,WR
中科院分区：
文献类型：
--
作者：
Gaudette,MF;Hampikian,G;Metelev,V;Agrawal,S;Crain,WR
将硫代磷酸修饰的寡核苷酸注射到怀孕的雌性小鼠中，以评估对发育中的胚胎的影响。在两个不同的时间段进行注射，一个是胚胎处于着床前发育阶段（发育约3.5天），另一个是着床后，胎儿和胎盘都存在时（发育9.5至11.5天）。注射三种不同的硫代磷酸酯修饰的寡核苷酸。其中一个序列在小鼠基因组中不存在，被用来询问是否对胚胎的非特异性毒性或致畸作用是由母亲的治疗引起的。第二个是与睾丸决定因子基因Sry的mRNA互补的，用于询问是否有特定的发育途径（即，性别决定）在胚胎体内可能被破坏。第三个是反Sry序列的互补序列。这些寡核苷酸均未降低交配后成功妊娠的频率或对照动物中观察到的平均窝仔数。此外，对所有注射利司那肽的妊娠雌性动物的291只幼仔或胎仔进行检查，未发现发育缺陷，无论使用哪种序列。它的结论是，注射硫代磷酸酯修饰的寡核苷酸到怀孕的女性根据这里描述的协议是没有毒性或致畸性的胚胎在一个非特异性的方式。此外，抗Sry寡核苷酸不影响胚胎的性别决定，尽管对此有几种可能的解释。
Phosphorothioate-modified oligonucleotides were injected into pregnant female mice to assess the effect on developing embryos. Injections were carried out during two different time periods, one when embryos were in preimplantation stages of development (about 3.5 days of development) and the other after implantation, when both a fetus and placenta are present (from days 9.5 to 11.5 of development). Three different phosphorothioate-modified oligonucleotides were injected. One, which had a sequence not present in the mouse genome, was used to ask whether nonspecific toxic or teratogenic effects on embryos result from treatment of the mother. A second was complementary to the mRNA of the testis-determining factor geneSryand was used to ask whether a specific developmental pathway (i.e., sex determination) could be disrupted in embryosin vivo. The third was the complement of the anti-Srysequence. None of these oligonucleotides reduced the frequency of successful pregnancy after mating or the average litter size from that observed in controls animals. Furthermore, examination of 291 pups or fetuses from all oligonucleotide-injected pregnant females revealed no developmental defects regardless of which sequence was used. It is concluded that injection of phosphorothioate-modified oligonucleotides into pregnant females according to the protocols described here is not toxic or teratogenic to embryos in a nonspecific way. Also, anti-Sryoligonucleotides did not influence sex determination in embryos, although there are several possible explanations for this.
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