Both obesity and gestational diabetes mellitus (GDM) lead to poor maternal and fetal outcomes, including pregnancy complications, fetal growth issues, stillbirth, and developmental programming of adult-onset disease in the offspring. Increased placental oxidative/nitrative stress and reduced placental (trophoblast) mitochondrial respiration occur in association with the altered maternal metabolic milieu of obesity and GDM. The effect is particularly evident when the fetus is male, suggesting a sexually dimorphic influence on the placenta. In addition, obesity and GDM are associated with inflexibility in trophoblast, limiting the ability to switch between usage of glucose, fatty acids, and glutamine as substrates for oxidative phosphorylation, again in a sexually dimorphic manner. Here we review mechanisms underlying placental mitochondrial dysfunction: its relationship to maternal and fetal outcomes and the influence of fetal sex. Prevention of placental oxidative stress and mitochondrial dysfunction may improve pregnancy outcomes. We outline pathways to ameliorate deficient mitochondrial respiration, particularly the benefits and pitfalls of mitochondria-targeted antioxidants.

肥胖和妊娠糖尿病 (GDM) 都会导致母婴结局不佳，包括妊娠并发症、胎儿生长问题、死产和后代成人发病的发育程序。胎盘氧化/硝化应激增加和胎盘（滋养层）线粒体呼吸减少与肥胖和 GDM 母体代谢环境的改变有关。当胎儿是男性时，这种影响尤其明显，这表明对胎盘的两性影响。此外，肥胖和 GDM 与滋养层细胞的僵化有关，限制了在使用葡萄糖、脂肪酸和谷氨酰胺作为氧化磷酸化底物之间切换的能力，同样以性别二态性方式。在这里，我们回顾了胎盘线粒体功能障碍的潜在机制：它与母胎结局的关系以及胎儿性别的影响。预防胎盘氧化应激和线粒体功能障碍可能会改善妊娠结局。我们概述了改善线粒体呼吸不足的途径，特别是针对线粒体的抗氧化剂的好处和缺陷。