No abstract

Maternal obesity is associated with increased oxidative stress but decreased placental mitochondrial respiration and expression of mitochondrial electron transport chain (ETC) complexes I to V. Melatonin acts as an antioxidant and prevents oxidative stress-induced changes in cytotrophoblasts. Placentas were collected at term by cesarean delivery from obese (first trimester body mass index [BMI] ≥30, n = 10) or lean (BMI < 25, n = 6) women. Cytotrophoblasts were isolated and allowed to syncytialize for 72 hours with or without melatonin (0.1-100 µM) for the last 24 hours. Mitochondrial respiratory parameters were measured in a Seahorse XF24. Expression of ETC complexes I to V and antioxidant enzymes was measured by Western blot. Maternal clinical characteristics of patients were similar except for BMI. No significant improvement in mitochondrial respiration occurred with addition of melatonin to trophoblasts of lean women. However, in trophoblasts from obese women, melatonin (10 and 100 µmol/L) significantly increased maximal respiration ( P = .01 and P = .009, respectively) and spare capacity ( P = .02 and P = .003, respectively) compared to the untreated control. No differences were detected in the expression of ETC complexes and superoxide dismutase 1 or 2 in trophoblasts treated with melatonin. The expression of glutathione peroxidase, which was significantly greater in trophoblast of obese compared to lean women ( P < .05), was decreased back to the level seen in trophoblast of lean women with addition of melatonin ( P = .02). Improved spare respiratory capacity, the cellular reserve, could impart a protective effect to the placenta and fetus in an adverse intrauterine environment or in response to additional stressors.

Rifampin may be an effective adjunctive therapy for intrahepatic cholestasis of pregnancy refractory to ursodiol alone. Additional research is needed to assess short-term and long-term maternal and newborn outcomes, because fetal deterioration still occurred in spite of maternal improvement.