关键词: IVF prognosis copy number mitochondrial DNA personalized infertility treatment ribosomal genes risk assessment telomere repeat

Mesh : Pregnancy Female Humans DNA Copy Number Variations / genetics Pilot Projects Fertilization in Vitro DNA, Mitochondrial / genetics DNA, Ribosomal Telomere Ovulation Induction / methods

来  源:   DOI:10.31083/j.fbs1503009

Abstract:
Individual risk assessment of assisted reproductive technologies is essential for personalized treatment strategies. Genetic and genomic indicators of the response to stress by cells could provide individual prognostic indicators for in vitro fertilization (IVF) success. Such indicators include the copy number of ribosomal genes (rDNA), which modulates the level of protein synthesis, and the abundance of mitochondrial DNA (mtDNA), which provides the cell with energy, while the content of telomere repeats (TRs) indicate the biological age.
The contents of the three repeats in DNA isolated from blood leukocytes of 40 women before and after ovarian stimulation were assayed prior to IVF. Then, we divided the women into a successful IVF group, IVF+ (N = 17, 7 cases of twins), and a group of failed cases, IVF- (N = 23). The control group included 17 non-pregnant women with natural childbirth in the past. The nonradioactive quantitative hybridization (NQH) method was applied to assay the genome repeat contents.
The number of rDNA copies in the IVF+ group was significantly higher than in the IVF- group (p < 10-8). The number of mtDNA copies in the IVF+ group also exceeded those in the IVF- group (p < 0.001), whereas the TR content in the two groups differed, albeit, non-significantly (p < 0.03). Following the ovarian stimulation, the rDNA copy numbers did not change, while the contents of the mtDNA and TR varied significantly.
This pilot study has shown that rDNA abundance in blood leukocytes can be considered a stable and effective predictor. Very low numbers of ribosomal repeat copies (<330) entail a high risk of IVF failure. However, a combination of numerous mtDNA and TRs, provided that rDNA content is not very low, increases the probability of multiple pregnancies.
摘要:
背景:辅助生殖技术的个体风险评估对于个性化治疗策略至关重要。细胞对应激反应的遗传和基因组指标可以为体外受精(IVF)成功提供个体预后指标。这些指标包括核糖体基因(rDNA)的拷贝数,调节蛋白质合成的水平,线粒体DNA(mtDNA)的丰度,为细胞提供能量,端粒重复序列(TRs)的含量表示生物年龄。
方法:在IVF前测定了40例女性卵巢刺激前后血液白细胞DNA中三个重复序列的含量。然后,我们把女性分成一个成功的试管婴儿组,IVF+(N=17,7例双胞胎),和一组失败的案例,IVF-(N=23)。对照组包括17名过去自然分娩的非孕妇。非放射性定量杂交(NQH)方法用于测定基因组重复序列的含量。
结果:IVF+组rDNA拷贝数明显高于IVF-组(p<10-8)。IVF+组的mtDNA拷贝数也超过IVF-组(p<0.001),而两组的TR含量不同,虽然,无显著性(p<0.03)。卵巢刺激后,rDNA拷贝数没有改变,而mtDNA和TR的含量差异显著。
结论:这项初步研究表明,血液白细胞中的rDNA丰度可以被认为是稳定和有效的预测因子。核糖体重复拷贝数非常低(<330)意味着IVF失败的风险很高。然而,许多mtDNA和TR的组合,只要rDNA含量不是很低,增加多胎妊娠的可能性。
公众号