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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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Detalles Bibliográficos
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
Descripción
Sumario: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.