Dataset Information

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

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.

SUBMITTER: Li L

PROVIDER: S-EPMC6215660 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Li Li L Wu Chang-Sheng CS Hou Guan-Mei GM Dong Ming-Zhe MZ Wang Zhen-Bo ZB Hou Yi Y Schatten Heide H Zhang Gui-Rong GR Sun Qing-Yuan QY

Reproductive biology and endocrinology : RB&E 20181103 1

<h4>Background</h4>Diabetes induces many complications including reduced fertility and low oocyte quality, but whether it causes increased mtDNA mutations is unknown.<h4>Methods</h4>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.<h4>Results</h4>T2D mice showed glucose intolerance, insulin resistance, low fecundity compared to the control group. T2D ooc ...[more]

PMID: 30390692

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Project description:During maturation oocytes undergo a recently discovered mitochondrial proteome remodeling event in flies1, frogs1, and humans2. This oocyte mitochondrial remodeling, which includes substantial changes in electron transport chain (ETC) subunit abundance1,2, is regulated by maternal insulin signaling1. Why oocytes undergo mitochondrial remodeling is unknown, with some speculating that it might be an evolutionarily conserved mechanism to protect oocytes from genotoxic damage by reactive oxygen species (ROS)2. In Caenorhabditis elegans, we previously found that maternal exposure to osmotic stress drives a 50-fold increase in offspring survival in response to future osmotic stress3. Like mitochondrial remodeling, we found that this intergenerational adaptation is also regulated by insulin signaling to oocytes3. Here, we used proteomics and genetic manipulations to show that insulin signaling to oocytes regulates offspring's ability to adapt to future stress via a mechanism that depends on ETC composition in maternal oocytes. Specifically, we found that maternally expressed mutant alleles of nduf-7 (complex I subunit) or isp-1 (complex III subunit) altered offspring's response to osmotic stress at hatching independently of offspring genotype. Furthermore, we found that expressing wild-type isp-1 in germ cells (oocytes) was sufficient to restore offspring's normal response to osmotic stress. Chemical mutagenesis screens revealed that maternal ETC composition regulates offspring's response to stress by altering AMP kinase function in offspring which in turn regulates both ATP and glycerol metabolism in response to continued osmotic stress. To our knowledge, these data are the first to show that proper oocyte ETC composition is required to link a mother's environment to adaptive changes in offspring metabolism. The data also raise the possibility that the reason diverse animals exhibit insulin regulated remodeling of oocyte mitochondria is to tailor offspring metabolism to best match the environment of their mother.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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