The effect of pre-existing maternal obesity and diabetes on placental mitochondrial content and electron transport chain activity

• Pre-existing maternal obesity is associated with placental mitochondrial changes.
• Pre-existing maternal diabetes is associated with placental mitochondrial changes.
• Pre-existing maternal obesity associates with lower placental mitochondrial content.
• Mitochondrial complex activity is lower in obese and diabetic placenta.
• There is increased mitochondrial oxidative stress in obese and diabetic placenta.

IntroductionMitochondria dysfunction has been extensively implicated in the progression of these metabolic disorders, their role in placental tissue of diabetic and/or obese pregnant women is yet to be investigated. The aim of this study was to determine the effect of pre-existing type 1 and type 2 diabetes mellitus (DM), and pre-existing maternal obesity on placental mitochondrial function as assessed by mitochondrial content, electron transport chain (ETC) complex activities and oxidative stress.MethodsHuman placenta was obtained at the time of term Caesarean section from (i) non-obese (n = 19) and obese (n = 23) normal glucose tolerant (NGT) pregnant women; (ii) women with type 1 DM (n = 14) and BMI-matched NGT women (n = 14); and (iii) women with type 2 DM (n = 11) and BMI-matched NGT women (n = 11). The following endpoints were assessed: placental mitochondrial content by citrate synthase activity and mitochondrial DNA (mtDNA content); mitochondrial respiratory chain activity (complexes I, II, II & III, III and IV), and mitochondrial ROS (as assessed by mitochondrial hydrogen peroxide (H2O2) levels).ResultsWhen compared to placenta from NGT non-obese women, there was significantly lower mitochondrial DNA (mtDNA) content and electron transport chain complex I activity, and significantly higher mitochondrial H2O2 levels in placenta from NGT obese women (P < 0.05). Placental tissue from type 1 DM women showed significant reductions in ETC complex I, II & III, and III activity and increased H2O2 levels when compared to BMI-matched NGT women (P < 0.05). Type 2 DM women only exhibited significantly reduced ETC complex II & III activity when compared to BMI-matched NGT women (P < 0.05).Discussion and conclusionsWomen with pre-existing obesity or diabetes have decreased placental mitochondrial respiratory chain enzyme activities which may have detrimental consequences on placental function and therefore fetal growth and development.