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. 2018 Nov 3;16(1):110.
doi: 10.1186/s12958-018-0423-1.

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

Li Li  1   2 , Chang-Sheng Wu  3 , Guan-Mei Hou  1   4 , Ming-Zhe Dong  1   2 , Zhen-Bo Wang  1   2 , Yi Hou  1 , Heide Schatten  5 , Gui-Rong Zhang  6 , Qing-Yuan Sun  7   8
Affiliations

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

Li Li et al. Reprod Biol Endocrinol. .

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.

Keywords: Bottleneck; Diabetes; Oocyte; mtDNA mutation.

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Conflict of interest statement

Ethics approval and consent to participate

All procedures described were reviewed and approved by the ethical committee of the Institute of Zoology, Chinese Academy of Sciences. All animal care and use procedures were in accordance with guidelines of the Institutional Animal Care and Use Committee of the Institute of Zoology, Chinese Academy of Sciences.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
A sketch of the T2D mouse model. (a) Body weight and (b) blood glucose were significantly increased (P<0.05) in T2D mice compared to the T2 DC group. (c) Glucose tolerance test (GTT) and (d) Insulin resistance test (ITT) at 16 weeks in T2D and T2 DC groups. T2D mice showed glucose intolerance and insulin resistance. After injection of STZ, at 20 weeks, glucose tolerance test (GTT) (e) and insulin resistance test (ITT) (f) are also seen in T2D mice. T2D mice showed persistent glucose intolerance and insulin resistance
Fig. 2
Fig. 2
T2D mouse model has a low fecundity. (a) The litter size was significantly decreased in T2D mice compared to the T2 DC group (P<0.05). (b) T2D-F1 newborn mice had a significantly higher malformation rate and significantly decreased low (c) birth weight compared to the T2 DC group (P<0.05)
Fig. 3
Fig. 3
T2D-F1 body weight and blood glucose. Female T2D-F1 group had significantly lower (a) body weight and (b) blood glucose (P<0.05) at weaning. At 7 weeks, female T2D-F1 mice showed significantly lower (c) body weight compared to female T2 DC-F1 mice. (d) Blood glucose in the two groups showed no difference in male\female mice. At 30 weeks, there were no differences in body weight (e), and blood glucose (f) between the two groups
Fig. 4
Fig. 4
GTT and ITT in growing F1 mice. (a) Female GTT and (b) ITT at 7 weeks, male (c) GTT and (d) ITT at 7 weeks. (e) Female GTT and (f) ITT at 30 weeks, male (g) GTT and (h) ITT at 30 weeks. At 7 or 30 weeks, female or male T2D-F1 mice showed no difference in glucose tolerance test and insulin resistance test
Fig. 5
Fig. 5
mtDNA mutations in oocytes. (a) mtDNA mutation sites and (b) mtDNA mutation numbers were increased in the T2D group compared to the T2 DC group. (c) mtDNA mutation sites and (d) mtDNA mutation numbers in the T2D-F1 group and the T2 DC-F1 group
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