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Published in: Reproductive Biology and Endocrinology 1/2018

Open Access 01-12-2018 | Research

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

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

Published in: Reproductive Biology and Endocrinology | Issue 1/2018

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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.
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Literature
1.
go back to reference Zhang CH, Qian WP, Qi ST, et al. Maternal diabetes causes abnormal dynamic changes of endoplasmic reticulum during mouse oocyte maturation and early embryo development[J]. Reprod Biol Endocrinol. 2013;11(1):31.CrossRef Zhang CH, Qian WP, Qi ST, et al. Maternal diabetes causes abnormal dynamic changes of endoplasmic reticulum during mouse oocyte maturation and early embryo development[J]. Reprod Biol Endocrinol. 2013;11(1):31.CrossRef
2.
go back to reference Vrachnis N, et al. Impact of maternal diabetes on epigenetic modifications leading to diseases in the offspring. Exp Diabetes Res. 2012;2012:538474.CrossRef Vrachnis N, et al. Impact of maternal diabetes on epigenetic modifications leading to diseases in the offspring. Exp Diabetes Res. 2012;2012:538474.CrossRef
3.
go back to reference Wyman A, et al. One-cell zygote transfer from diabetic to nondiabetic mouse results in congenital malformations and growth retardation in offspring. Endocrinol. 2008;149(2):466–9.CrossRef Wyman A, et al. One-cell zygote transfer from diabetic to nondiabetic mouse results in congenital malformations and growth retardation in offspring. Endocrinol. 2008;149(2):466–9.CrossRef
4.
go back to reference Cao L, et al. The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells. Nat Genet. 2007;39(3):386–90.CrossRef Cao L, et al. The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells. Nat Genet. 2007;39(3):386–90.CrossRef
5.
go back to reference Hauswirth WW, Laipis PJ. Mitochondrial DNA polymorphism in a maternal lineage of Holstein cows. Proc Natl Acad Sci U S A. 1982;79(15):4686–90.CrossRef Hauswirth WW, Laipis PJ. Mitochondrial DNA polymorphism in a maternal lineage of Holstein cows. Proc Natl Acad Sci U S A. 1982;79(15):4686–90.CrossRef
6.
go back to reference Wai T, Ao A, Zhang X, et al. The role of mitochondrial DNA copy number in mammalian Fertility1. Biol Reprod. 2010;83(1):52–62.CrossRef Wai T, Ao A, Zhang X, et al. The role of mitochondrial DNA copy number in mammalian Fertility1. Biol Reprod. 2010;83(1):52–62.CrossRef
7.
go back to reference Jiang J, et al. Mitochondrial genome and nuclear markers provide new insight into the evolutionary history of macaques. PLoS One. 2016;11(5):e0154665.CrossRef Jiang J, et al. Mitochondrial genome and nuclear markers provide new insight into the evolutionary history of macaques. PLoS One. 2016;11(5):e0154665.CrossRef
8.
go back to reference Rossignol R, Faustin B, Rocher C, et al. Mitochondrial threshold effects. Biochem J. 2003;370(3):751–62.CrossRef Rossignol R, Faustin B, Rocher C, et al. Mitochondrial threshold effects. Biochem J. 2003;370(3):751–62.CrossRef
9.
go back to reference Tian Y, Merkwirth C, Dillin A. Mitochondrial UPR: a double-edged sword. Trends Cell Biol. 2016;26(8):563–5.CrossRef Tian Y, Merkwirth C, Dillin A. Mitochondrial UPR: a double-edged sword. Trends Cell Biol. 2016;26(8):563–5.CrossRef
10.
go back to reference Sacconi S, et al. A functionally dominant mitochondrial DNA mutation. Hum Mol Genet. 2008;17(12):1814–20.CrossRef Sacconi S, et al. A functionally dominant mitochondrial DNA mutation. Hum Mol Genet. 2008;17(12):1814–20.CrossRef
11.
go back to reference He Y, et al. Heteroplasmic mitochondrial DNA mutations in normal and tumour cells. Nature. 2010;464(7288):610–4.CrossRef He Y, et al. Heteroplasmic mitochondrial DNA mutations in normal and tumour cells. Nature. 2010;464(7288):610–4.CrossRef
12.
go back to reference Payne BA, et al. Universal heteroplasmy of human mitochondrial DNA. Hum Mol Genet. 2013;22(2):384–90.CrossRef Payne BA, et al. Universal heteroplasmy of human mitochondrial DNA. Hum Mol Genet. 2013;22(2):384–90.CrossRef
13.
go back to reference Fan W, Waymire KG, Narula N, et al. A mouse model of mitochondrial disease reveals germline selection against severe mtDNA mutations. Sci. 2008;319(5865):958–62.CrossRef Fan W, Waymire KG, Narula N, et al. A mouse model of mitochondrial disease reveals germline selection against severe mtDNA mutations. Sci. 2008;319(5865):958–62.CrossRef
14.
go back to reference Stewart JB, Freyer C, Elson JL, et al. Strong purifying selection in transmission of mammalian mitochondrial DNA. PLoS Biol. 2008;6(1):e10.CrossRef Stewart JB, Freyer C, Elson JL, et al. Strong purifying selection in transmission of mammalian mitochondrial DNA. PLoS Biol. 2008;6(1):e10.CrossRef
15.
go back to reference Luo J, Quan J, Tsai J, et al. Nongenetic mouse models of non-insulin-dependent diabetes mellitus. Metab Clin Exp. 1998;47(6):663–8.CrossRef Luo J, Quan J, Tsai J, et al. Nongenetic mouse models of non-insulin-dependent diabetes mellitus. Metab Clin Exp. 1998;47(6):663–8.CrossRef
16.
go back to reference Wei Y, Yang CR, Wei YP, et al. Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals. Proc Natl Acad Sci U S A. 2014;111(5):1873–8.CrossRef Wei Y, Yang CR, Wei YP, et al. Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals. Proc Natl Acad Sci U S A. 2014;111(5):1873–8.CrossRef
17.
go back to reference Langmead B, Trapnell C, Pop M, et al. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009;10(3):R25.CrossRef Langmead B, Trapnell C, Pop M, et al. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009;10(3):R25.CrossRef
18.
go back to reference Li H, et al. The sequence alignment/map format and SAMtools. Bioinformatics. 2009;25(16):2078–9.CrossRef Li H, et al. The sequence alignment/map format and SAMtools. Bioinformatics. 2009;25(16):2078–9.CrossRef
19.
go back to reference Li H. A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinformatics. 2011;27(21):2987–93.CrossRef Li H. A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinformatics. 2011;27(21):2987–93.CrossRef
20.
go back to reference McLaren W, et al. The Ensembl variant effect predictor. Genome Biol. 2016;17(1):122.CrossRef McLaren W, et al. The Ensembl variant effect predictor. Genome Biol. 2016;17(1):122.CrossRef
21.
go back to reference Abuaisha B, Kumar S, Malik R, et al. Relationship of elevated urinary albumin excretion to components of the metabolic syndrome in non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract. 1998;39(2):93.CrossRef Abuaisha B, Kumar S, Malik R, et al. Relationship of elevated urinary albumin excretion to components of the metabolic syndrome in non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract. 1998;39(2):93.CrossRef
22.
go back to reference Pamir N, Lynn FC, Buchan AM, et al. Glucose-dependent insulinotropic polypeptide receptor null mice exhibit compensatory changes in the enteroinsular axis. Am J Physiol Endocrinol Metab. 2003;284(5):E931.CrossRef Pamir N, Lynn FC, Buchan AM, et al. Glucose-dependent insulinotropic polypeptide receptor null mice exhibit compensatory changes in the enteroinsular axis. Am J Physiol Endocrinol Metab. 2003;284(5):E931.CrossRef
23.
go back to reference Isidro ML. Sexual dysfunction in men with type 2 diabetes. Postgrad Med J. 2012;88(1037):152–9.CrossRef Isidro ML. Sexual dysfunction in men with type 2 diabetes. Postgrad Med J. 2012;88(1037):152–9.CrossRef
24.
go back to reference Navarro-Casado L, Juncos-Tobarra MA, Cháfer-Rudilla M, et al. Effect of experimental diabetes and STZ on male fertility capacity. Study in rats. J Androl. 2010;31(6):584–92.CrossRef Navarro-Casado L, Juncos-Tobarra MA, Cháfer-Rudilla M, et al. Effect of experimental diabetes and STZ on male fertility capacity. Study in rats. J Androl. 2010;31(6):584–92.CrossRef
25.
go back to reference Gokina NI, Bonev AD, Gokin AP, et al. Role of impaired endothelial cell ca(2+) signaling in uteroplacental vascular dysfunction during diabetic rat pregnancy. Am J Physiol Heart Circ Physiol. 2013;304(7):H935.CrossRef Gokina NI, Bonev AD, Gokin AP, et al. Role of impaired endothelial cell ca(2+) signaling in uteroplacental vascular dysfunction during diabetic rat pregnancy. Am J Physiol Heart Circ Physiol. 2013;304(7):H935.CrossRef
26.
go back to reference Suttonmcdowall ML, Gilchrist RB, Thompson JG. The pivotal role of glucose metabolism in determining oocyte developmental competence. Reproduction. 2010;139(4):685–95.CrossRef Suttonmcdowall ML, Gilchrist RB, Thompson JG. The pivotal role of glucose metabolism in determining oocyte developmental competence. Reproduction. 2010;139(4):685–95.CrossRef
27.
go back to reference Wang Q, Moley KH. Maternal diabetes and oocyte quality. Mitochondrion. 2010;10(5):403–10.CrossRef Wang Q, Moley KH. Maternal diabetes and oocyte quality. Mitochondrion. 2010;10(5):403–10.CrossRef
28.
go back to reference Vrachnis N, Antonakopoulos N, Iliodromiti Z, et al. Impact of maternal diabetes on epigenetic modifications leading to diseases in the offspring. Exp Diabetes Res. 2012;2012(8):538474.PubMedPubMedCentral Vrachnis N, Antonakopoulos N, Iliodromiti Z, et al. Impact of maternal diabetes on epigenetic modifications leading to diseases in the offspring. Exp Diabetes Res. 2012;2012(8):538474.PubMedPubMedCentral
29.
go back to reference Ozanne SE, Hales CN. Lifespan: catch-up growth and obesity in male mice. Nature. 2004;427(6973):411–2.CrossRef Ozanne SE, Hales CN. Lifespan: catch-up growth and obesity in male mice. Nature. 2004;427(6973):411–2.CrossRef
30.
go back to reference Morimoto S, Sosa TC, Calzada L, et al. Developmental programming of aging of isolated pancreatic islet glucose-stimulated insulin secretion in female offspring of mothers fed low-protein diets in pregnancy and/or lactation. J Dev Orig Health Dis. 2012;3(6):483–8.CrossRef Morimoto S, Sosa TC, Calzada L, et al. Developmental programming of aging of isolated pancreatic islet glucose-stimulated insulin secretion in female offspring of mothers fed low-protein diets in pregnancy and/or lactation. J Dev Orig Health Dis. 2012;3(6):483–8.CrossRef
31.
go back to reference Holt IJ, Harding AE, Morganhughes JA. Deletions of muscle mitochondrial DNA in mitochondrial myopathies: sequence analysis and possible mechanisms. Nucleic Acids Res. 1989;17(12):4465.CrossRef Holt IJ, Harding AE, Morganhughes JA. Deletions of muscle mitochondrial DNA in mitochondrial myopathies: sequence analysis and possible mechanisms. Nucleic Acids Res. 1989;17(12):4465.CrossRef
32.
go back to reference Wallace DC, Singh G, Lott MT, et al. Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science. 1988;242(4884):1427–30.CrossRef Wallace DC, Singh G, Lott MT, et al. Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science. 1988;242(4884):1427–30.CrossRef
33.
go back to reference Manwaring N, Jones MM, Wang JJ, et al. Population prevalence of the MELAS A3243G mutation. Mitochondrion. 2007;7(3):230–3.CrossRef Manwaring N, Jones MM, Wang JJ, et al. Population prevalence of the MELAS A3243G mutation. Mitochondrion. 2007;7(3):230–3.CrossRef
34.
go back to reference Gorman GS, Schaefer AM, Ng Y, et al. Prevalence of nuclear and mtDNA mutations related to adult mitochondrial disease. Ann Neurol. 2015;77(5):753–9.CrossRef Gorman GS, Schaefer AM, Ng Y, et al. Prevalence of nuclear and mtDNA mutations related to adult mitochondrial disease. Ann Neurol. 2015;77(5):753–9.CrossRef
35.
go back to reference Chinnery PF, Johnson MA, Wardell TM, et al. The epidemiology of pathogenic mitochondrial DNA mutations. Ann Neurol. 2000;48(2):1097–102.CrossRef Chinnery PF, Johnson MA, Wardell TM, et al. The epidemiology of pathogenic mitochondrial DNA mutations. Ann Neurol. 2000;48(2):1097–102.CrossRef
36.
go back to reference Alan D, Eszter D, Tiffany L, et al. Modulating mitochondrial quality in disease transmission: towards enabling mitochondrial DNA disease carriers to have healthy children. Biochem Soc Trans. 2016;44(4):1091–100.CrossRef Alan D, Eszter D, Tiffany L, et al. Modulating mitochondrial quality in disease transmission: towards enabling mitochondrial DNA disease carriers to have healthy children. Biochem Soc Trans. 2016;44(4):1091–100.CrossRef
37.
go back to reference Chen H, Vermulst M, Wang YE, et al. Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations. Cell. 2010;141(2):280.CrossRef Chen H, Vermulst M, Wang YE, et al. Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations. Cell. 2010;141(2):280.CrossRef
38.
go back to reference Tam ZY, Gruber J, Halliwell B, et al. Context-dependent role of mitochondrial fusion-fission in clonal expansion of mtDNA mutations. PLoS Comput Biol. 2015;11(5):e1004183.CrossRef Tam ZY, Gruber J, Halliwell B, et al. Context-dependent role of mitochondrial fusion-fission in clonal expansion of mtDNA mutations. PLoS Comput Biol. 2015;11(5):e1004183.CrossRef
39.
go back to reference Otten AB, Smeets HJ. Evolutionary defined role of the mitochondrial DNA in fertility, disease and ageing. Hum Reprod Update. 2015;5:671–89.CrossRef Otten AB, Smeets HJ. Evolutionary defined role of the mitochondrial DNA in fertility, disease and ageing. Hum Reprod Update. 2015;5:671–89.CrossRef
Metadata
Title
Type 2 diabetes increases oocyte mtDNA mutations which are eliminated in the offspring by bottleneck effect
Authors
Li Li
Chang-Sheng Wu
Guan-Mei Hou
Ming-Zhe Dong
Zhen-Bo Wang
Yi Hou
Heide Schatten
Gui-Rong Zhang
Qing-Yuan Sun
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2018
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-018-0423-1

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