Diabetes, myometrium, and mitochondria in pregnant women at term

Abstract

Aims

Poor myometrial contractility has been demonstrated in women at term with diabetes and decreased muscular mitochondrial content and/or function has been extensively implicated in the progression of type 2 diabetes. Alterations of the uterine mitochondrial phenotype in pregnant women with diabetes have yet to be investigated as a causal link to decreased myometrial contractility.

Methods

Observational study of 18 women with diabetes (type 2 and gestational) scheduled for an elective Caesarean section at term with matching controls. A uterine biopsy and fasting blood samples were taken on the day of delivery.

Results

Respiration rates in isolated mitochondria and myometrial mRNA levels of genes related to mitochondrial biogenesis were unaffected by diabetes. Mitochondrial quantity examined by quantification of the complexes of the respiratory chain and histology did not indicate alterations in mitochondrial quantity. Citrate syntase activity was higher (0.31 ± 0.02 vs. 0.24 ± 0.02 U/mg protein, P = 0.008), whereas protein content was lower in women with diabetes compared with the control group (94.6 ± 6.9 vs. 118.6 ± 7.4 mg/g wet wt, P = 0.027). Histological examinations did not support any structural alterations in the myometrium or its mitochondria.

Conclusion

No indication of decreased mitochondrial function, content, morphology, or localization in the myometrium at term in women with diabetes compared with controls was observed. The increase in citrate syntase activity in the myometrium could be explained by the lower protein content in the myometrium, which we suggest is due to alterations in tissue or cellular composition.

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Acknowledgements

We thank Mr. Ib Therkelsen, Panum NMR Center, and Mrs. Bettina Starup Mentz, Section for Cellular and Metabolic Research, for expert technical assistance during the conductance of the experiments. We also thank Ms. Zhila Nikrozi, Core Facility for Integrated Microscopy, and Mrs. Heidi Marie Paulsen, Endocrinology Research Section, for expert technical assistance in section preparation for electron microscopy and light microscopy, respectively. The study is part of Christiane Gam’s Ph.D. project funded by the Faculty of Health and Medical Sciences, University of Copenhagen, and by Ph.D. program of Diabetes and Metabolism, Faculty of Health Sciences, University of Southern Denmark.

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Authors

Contributions

CG, BQ, PD, OM, and LL planned and designed the study. CG, PD, and EM were responsible for subject inclusion. CG acquired the blood and tissue samples. CG conducted the mitochondrial respiratory experiments. CG, KQ, and SP conducted the histological analyses. CG, OM, and LL conducted the biochemical analyses, including gene and protein expression analyses. CG and OM did the statistical analyses. All authors contributed in writing the manuscript and coordination of the correspondence between authors was organized by CG.

Corresponding author

Correspondence to Christiane Marie Bourgin Folke Gam.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.The study was approved by the regional ethical committee of Copenhagen, Denmark (Protocol No. H-1-2012-070).

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Informed consent was obtained from all individual participants included in the study.

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Gam, C.M.B.F., Mortensen, O.H., Larsen, L.H. et al. Diabetes, myometrium, and mitochondria in pregnant women at term. Acta Diabetol 55, 999–1010 (2018). https://doi.org/10.1007/s00592-018-1171-6

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Keywords

  • Diabetes
  • Myometrium
  • Mitochondria
  • Dystocia