Mitochondria Respiration in the Placental Villi Tissue of Obese and Normal-Weight Women

BACKGROUND: Maternal obesity (MO) is a risk factor for short and long-term poor outcomes, for both the mother and the offspring. Placental oxidative stress is typical in MO, and mitochondria (mt) dysfunction has been shown in placental trophoblasts. We previously showed decreased placental villi respiratory chain (RC) complexes and ATP production. Here, we measured mt respiration in the villi complete tissue. METHODS: Obese women (OB) were specifically counseled for a correct nutrition and lifestyle, to reach IOM gestational weight gain (GWG) recommendations. Placental villi from single healthy pregnancies of women with pre-pregnancy BMI 30 (OB, n=6) or 18.5-25 (NW, n=5) were collected at elective cesarean section, stored in BIOPS and cryopreserved. Oxygen (O2) Consumption Rates (OCRs) of mt was determined by High-Resolution Respirometry (HRR, O2K Oroboros Instruments), measuring LEAK state (resting state), mt Complex I and II OXPHOS capacity (O2 consumption linked to ATP production), maximal respiratory capacity of the Electon Transfer System (ETS) and mt Complex IV (CIV) activity. RESULTS: Maternal and gestational age, neonatal and placental weight were similar in OB and NW. GWG was lower in OB, though not significantly. HRR analysis displayed impaired mt activity in OB villi with a significant reduction of CI+CII OXPHOS coupled and of maximal ETS capacities. Accordingly, chemical CIV activation showed a defect in CIV in OB placentas (Fig1). Interestingly, maternal BMI negatively correlated with all parameters of O2 consumption, reaching significance for CI+CII (p=0.02 r=-0.7), ETS (p=0.01 r=-0.7), CIV (p=0.01 r=-0.7). DISCUSSION: To our knowledge these are the first data exploring the RC function in the placental villi tissue of OB pregnancies by HRR that allows precise and standardized measurement of cell populations organized in the complex placental villi structure. Although OB were specifically counseled, gaining less weight, their placentas showed significantly lower O2 consumption, inversely correlated with maternal BMI. This is in line with our previous results, showing in OB decreased placental RC complex I, III, V and reduced ATP production. These results provide a complete readout of mt function in the OB placental tissue, being possibly implicated in the metabolic disorder progression. Prevention of mt dysfunction by ameliorating RC respiration might improve OB outcomes. Further research is needed to outline mitochondria-targeted therapies.