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

Li Li,Qing-Yuan Sun,Guan-Mei Hou,Gui-Rong Zhang,Chang-Sheng Wu,Yi Hou,Zhen-Bo Wang,Ming-Zhe Dong,Heide Schatten

doi:10.1186/s12958-018-0423-1

Abstract

BackgroundDiabetes induces many complications including reduced fertility and low oocyte quality, but whether it causes increased mtDNA mutations is unknown.MethodsWe 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.ResultsT2D 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.ConclusionsT2D 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.

Highlights

Diabetes induces many complications including reduced fertility and low oocyte quality, but whether it causes increased Mitochondrial DNA (mtDNA) mutations is unknown
We showed that mtDNA mutations increased in the type 2 diabetes (T2D) mouse model, but the mitochondrial bottleneck could bring clearance of mtDNA mutations in the offspring
Establishment of the diabetes mouse model To explore the effect of diabetes on oocyte mtDNA mutations, we generated a T2D mouse model

Summary

Introduction

Diabetes induces many complications including reduced fertility and low oocyte quality, but whether it causes increased mtDNA mutations is unknown. 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. Women with diabetes mellitus often show low quality oocytes, increased chances of miscarriage, and congenital malformations of offspring [1, 2].

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Results

Conclusion