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

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 oocy...

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Autores principales: Li, Li, Wu, Chang-Sheng, Hou, Guan-Mei, Dong, Ming-Zhe, Wang, Zhen-Bo, Hou, Yi, Schatten, Heide, Zhang, Gui-Rong, Sun, Qing-Yuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215660/
https://www.ncbi.nlm.nih.gov/pubmed/30390692
http://dx.doi.org/10.1186/s12958-018-0423-1
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author Li, Li
Wu, Chang-Sheng
Hou, Guan-Mei
Dong, Ming-Zhe
Wang, Zhen-Bo
Hou, Yi
Schatten, Heide
Zhang, Gui-Rong
Sun, Qing-Yuan
author_facet Li, Li
Wu, Chang-Sheng
Hou, Guan-Mei
Dong, Ming-Zhe
Wang, Zhen-Bo
Hou, Yi
Schatten, Heide
Zhang, Gui-Rong
Sun, Qing-Yuan
author_sort Li, Li
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12958-018-0423-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-62156602018-11-08 Type 2 diabetes increases oocyte mtDNA mutations which are eliminated in the offspring by bottleneck effect Li, Li Wu, Chang-Sheng Hou, Guan-Mei Dong, Ming-Zhe Wang, Zhen-Bo Hou, Yi Schatten, Heide Zhang, Gui-Rong Sun, Qing-Yuan Reprod Biol Endocrinol Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12958-018-0423-1) contains supplementary material, which is available to authorized users. BioMed Central 2018-11-03 /pmc/articles/PMC6215660/ /pubmed/30390692 http://dx.doi.org/10.1186/s12958-018-0423-1 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Li, Li
Wu, Chang-Sheng
Hou, Guan-Mei
Dong, Ming-Zhe
Wang, Zhen-Bo
Hou, Yi
Schatten, Heide
Zhang, Gui-Rong
Sun, Qing-Yuan
Type 2 diabetes increases oocyte mtDNA mutations which are eliminated in the offspring by bottleneck effect
title Type 2 diabetes increases oocyte mtDNA mutations which are eliminated in the offspring by bottleneck effect
title_full Type 2 diabetes increases oocyte mtDNA mutations which are eliminated in the offspring by bottleneck effect
title_fullStr Type 2 diabetes increases oocyte mtDNA mutations which are eliminated in the offspring by bottleneck effect
title_full_unstemmed Type 2 diabetes increases oocyte mtDNA mutations which are eliminated in the offspring by bottleneck effect
title_short Type 2 diabetes increases oocyte mtDNA mutations which are eliminated in the offspring by bottleneck effect
title_sort type 2 diabetes increases oocyte mtdna mutations which are eliminated in the offspring by bottleneck effect
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215660/
https://www.ncbi.nlm.nih.gov/pubmed/30390692
http://dx.doi.org/10.1186/s12958-018-0423-1
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