Ireland Kayla E, Maloyan Alina, Myatt Leslie
1 Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
2 Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Reprod Sci. 2018 Jan;25(1):120-130. doi: 10.1177/1933719117704908. Epub 2017 Apr 26.
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.
母体肥胖与氧化应激增加相关，但胎盘线粒体呼吸以及线粒体电子传递链（ETC）复合体I至V的表达降低。褪黑素作为一种抗氧化剂，可防止氧化应激诱导的细胞滋养层细胞变化。通过剖宫产在足月时收集肥胖（孕早期体重指数[BMI]≥30，n = 10）或瘦（BMI < 25，n = 6）女性的胎盘。分离细胞滋养层细胞，并在最后24小时内使其在有或没有褪黑素（0.1 - 100 μM）的情况下同步化72小时。使用海马XF24测量线粒体呼吸参数。通过蛋白质免疫印迹法测量ETC复合体I至V和抗氧化酶的表达。除BMI外，患者的母体临床特征相似。在瘦女性的滋养层细胞中添加褪黑素后，线粒体呼吸没有显著改善。然而，在肥胖女性的滋养层细胞中，与未处理的对照组相比，褪黑素（10和100 μmol/L）显著增加了最大呼吸（分别为P = 0.01和P = 0.009）和备用容量（分别为P = 0.02和P = 0.003）。在用褪黑素处理的滋养层细胞中，未检测到ETC复合体以及超氧化物歧化酶1或2的表达差异。与瘦女性的滋养层细胞相比，肥胖女性的滋养层细胞中谷胱甘肽过氧化物酶的表达显著更高（P < 0.05），添加褪黑素后其表达降低至瘦女性的滋养层细胞中的水平（P = 0.02）。改善的备用呼吸容量，即细胞储备，可在不利的子宫内环境中或应对额外应激源时对胎盘和胎儿起到保护作用。
