Diabetes, myometrium, and mitochondria in pregnant women at term.

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.

Unchanged mitochondrial phenotype, but accumulation of lipids in the myometrium in obese pregnant women.

KEY POINTS: Obesity during pregnancy and childbirth is associated with labour dystocia leading to instrumental or operative delivery, but the underlying pathophysiological mechanisms remain unclear and insufficient uterine contractility has been suggested. This study examined whether reduced myometrial mitochondrial capacity or quantity could contribute as a pathophysiological mechanism to labour dystocia. Data did not support reduced myometrial mitochondrial capacity or quantity in the myometrium at term in obese women, but a reduced myocyte density with increased triglyceride content was demonstrated, which could lead to poorer uterine contractility. These results add to the understanding of systemic effects of obesity, placing also the myometrium at term as an affected non-adipose tissue. ABSTRACT: Obesity is known to increase the risk of labour dystocia and insufficient energy supply, due to reduced mitochondrial capacity or quantity, could be a possible mechanism leading to reduced efficiency of uterine contractility during labour. In the present study of 36 women having an elective Caesarean section at term, obesity did not change mitochondrial phenotype in the myometrial myocyte obtained from uterine biopsies taken at delivery. Respiration rates in isolated mitochondria were unaffected by obesity. No indication of reduced content, investigated by quantification of the complexes of the respiratory chain, or altered regulation, examined by myometrial mRNA levels of genes related to mitochondrial biogenesis and inflammation, was detected. Yet we found increased myometrial triglyceride content in the obese group (2.39 ± 0.26 vs. 1.56 ± 0.20 mm, P = 0.024), while protein content and citrate synthase activity per gram wet weight myometrium were significantly lower in the obese (109.2 ± 7.2 vs. 139.4 ± 5.6 mg g-1 , P = 0.002, and 24.8 ± 1.0 vs. 29.6 ± 1.4 U g-1 wet wt, P = 0.008, respectively). These differences were substantiated by our histological findings where staining for nuclei, cytoplasm, glycogen and collagen supported the idea of a smaller muscle content in the myometrium in obese women. In conclusion no indication of myometrial mitochondrial dysfunction in the isolated state was found, but the observed increase of lipid content might play a role in the pathophysiological mechanisms behind labour dystocia in obese women.

Effect of high-fat diet on rat myometrium during pregnancy-isolated myometrial mitochondria are not affected.

Laboring women with elevated body mass index (BMI) have an increased risk of inefficient uterine labor contractions, and despite the significance of mitochondria in the production of energy to drive uterine contractions, mitochondrial function in the myometrium with reference to the BMI has not been explored. The objective of this study was to determine whether obesity prior to and during gestation affects oxidative capacity and/or morphology of mitochondria in the myometrium at term in an animal model. Rat dams were fed for 47 days prior to impregnation and during gestation with either (1) a regular chow diet, (2) a low-fat high-carbohydrate diet, or (3) a high-fat low-carbohydrate diet (n = 10 in each group). On day 20 of gestation, corresponding to term pregnancy, total hysterectomy was performed with subsequent examination of the function and morphology of myometrial mitochondria. Body composition was regularly assessed by quantitative magnetic resonance imaging, and blood sampling was done prior to diet assignment, impregnation, and hysterectomy. Dams on the high-fat low-carbohydrate diet achieved higher fat percentage compared to rats on the regular chow diet (p < 0.05). Maximal oxygen consumption, phosphate/oxygen ratio, or the amount of mitochondria per gram of myometrium did not differ between the three feeding groups. Electron microscopic examinations did not reveal any morphological differences in mitochondria between groups; however, a previously undescribed subsarcolemmal localization of the mitochondria in the myocyte was identified. We did not find evidence of altered myometrial mitochondrial function or morphology in this animal model of obesity prior to and during pregnancy.