Li Li1,2, Chang-Sheng Wu3, Guan-Mei Hou1,4, Ming-Zhe Dong1,2, Zhen-Bo Wang1,2, Yi Hou1, Heide Schatten5, Gui-Rong Zhang6, Qing-Yuan Sun7,8. 1. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. 2. University of Chinese Academy of Sciences, Beijing, 100101, China. 3. Peking Medriv Academy of Genetics and Reproduction, Beijing, 102629, China. 4. College of Life Science, Qingdao Agricultural University, Qingdao, 266109, China. 5. Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, 65211, USA. 6. Peking Medriv Academy of Genetics and Reproduction, Beijing, 102629, China. guirong_zhang@126.com. 7. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. sunqy1@yahoo.com. 8. University of Chinese Academy of Sciences, Beijing, 100101, China. sunqy1@yahoo.com.
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.
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 diabeticmice 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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