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2 型糖尿病会增加卵母细胞 mtDNA 突变,这些突变会通过瓶颈效应在后代中被消除。

Type 2 diabetes increases oocyte mtDNA mutations which are eliminated in the offspring by bottleneck effect.

机构信息

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.

University of Chinese Academy of Sciences, Beijing, 100101, China.

出版信息

Reprod Biol Endocrinol. 2018 Nov 3;16(1):110. doi: 10.1186/s12958-018-0423-1.

Abstract

BACKGROUND

Diabetes induces many complications including reduced fertility and low oocyte quality, but whether it causes increased mtDNA mutations is unknown.

METHODS

We generated a T2D mouse model by using high-fat-diet (HFD) and Streptozotocin (STZ) injection. We examined mtDNA mutations in oocytes of diabetic mice by high-throughput sequencing techniques.

RESULTS

T2D mice showed glucose intolerance, insulin resistance, low fecundity compared to the control group. T2D oocytes showed increased mtDNA mutation sites and mutation numbers compared to the control counterparts. mtDNA mutation examination in F1 mice showed that the mitochondrial bottleneck could eliminate mtDNA mutations.

CONCLUSIONS

T2D mice have increased mtDNA mutation sites and mtDNA mutation numbers in oocytes compared to the counterparts, while these adverse effects can be eliminated by the bottleneck effect in their offspring. This is the first study using a small number of oocytes to examine mtDNA mutations in diabetic mothers and offspring.

摘要

背景

糖尿病会引起许多并发症,包括生育能力降低和卵母细胞质量下降,但它是否会导致线粒体 DNA 突变增加尚不清楚。

方法

我们通过高脂肪饮食(HFD)和链脲佐菌素(STZ)注射建立了 2 型糖尿病小鼠模型。我们通过高通量测序技术检测了糖尿病小鼠卵母细胞中的 mtDNA 突变。

结果

与对照组相比,2 型糖尿病小鼠表现出葡萄糖不耐受、胰岛素抵抗和低生育力。与对照组相比,2 型糖尿病卵母细胞的 mtDNA 突变位点和突变数量增加。F1 代小鼠的 mtDNA 突变检测表明,线粒体瓶颈可以消除 mtDNA 突变。

结论

与对照组相比,2 型糖尿病小鼠的卵母细胞中 mtDNA 突变位点和 mtDNA 突变数量增加,而这些不利影响可以通过其后代的瓶颈效应消除。这是第一项使用少量卵母细胞检测糖尿病母亲及其后代 mtDNA 突变的研究。

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