Pregnancy complications associated with prenatal hypoxia lead to increased placental oxidative stress. Previous studies suggest that prenatal hypoxia can reduce mitochondrial respiratory capacity and mitochondrial fusion, which could lead to placental dysfunction and impaired fetal development. We developed a placenta-targeted treatment strategy using a mitochondrial antioxidant, MitoQ, encapsulated into nanoparticles (nMitoQ) to reduce placental oxidative stress and (indirectly) improve fetal outcomes. We hypothesized that, in a rat model of prenatal hypoxia, nMitoQ improves placental mitochondrial function and promotes mitochondrial fusion in both male and female placentae. Pregnant rats were treated with saline or nMitoQ on gestational day (GD) 15 and exposed to normoxia (21% O2 ) or hypoxia (11% O2 ) from GD15-21. On GD21, male and female placental labyrinth zones were collected for mitochondrial respirometry assessments, mitochondrial content, and markers of mitochondrial biogenesis, fusion and fission. Prenatal hypoxia reduced complex IV activity and fusion in male placentae, while nMitoQ improved complex IV activity in hypoxic male placentae. In female placentae, prenatal hypoxia decreased respiration through the S-pathway (complex II) and increased N-pathway (complex I) respiration, while nMitoQ increased fusion in hypoxic female placentae. No changes in mitochondrial content, biogenesis or fission were found. In conclusion, nMitoQ improved placental mitochondrial function in male and female placentae from fetuses exposed to prenatal hypoxia, which may contribute to improved placental function. However, the mechanisms (ie, changes in mitochondrial respiratory capacity and mitochondrial fusion) were distinct between the sexes. Treatment strategies targeted against placental oxidative stress could improve placental mitochondrial function in complicated pregnancies.

中文翻译：

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纳米颗粒包裹的抗氧化剂在产前缺氧大鼠模型中以性别二态性方式改善胎盘线粒体功能

与产前缺氧相关的妊娠并发症会导致胎盘氧化应激增加。先前的研究表明，产前缺氧会降低线粒体呼吸能力和线粒体融合，从而导致胎盘功能障碍和胎儿发育受损。我们开发了一种胎盘靶向治疗策略，使用线粒体抗氧化剂 MitoQ，将其封装在纳米粒子 (nMitoQ) 中，以减少胎盘氧化应激并（间接）改善胎儿结局。我们假设，在产前缺氧的大鼠模型中，nMitoQ 可改善胎盘线粒体功能并促进男性和女性胎盘的线粒体融合。在妊娠第 15 天 (GD) 用盐水或 nMitoQ 处理怀孕的大鼠，并从 GD15-21 暴露于常氧 (21% O2) 或缺氧 (11% O2)。在 GD21 上，收集雄性和雌性胎盘迷路区用于线粒体呼吸测量评估、线粒体含量以及线粒体生物发生、融合和裂变的标志物。产前缺氧降低了男性胎盘中复合体 IV 的活性和融合，而 nMitoQ 改善了缺氧男性胎盘中的复合体 IV 活性。在女性胎盘中，产前缺氧通过 S 通路（复合物 II）减少呼吸，增加 N 通路（复合物 I）呼吸，而 nMitoQ 增加缺氧女性胎盘中的融合。未发现线粒体含量、生物发生或裂变发生变化。总之，nMitoQ 改善了暴露于产前缺氧的胎儿的男性和女性胎盘的胎盘线粒体功能，这可能有助于改善胎盘功能。然而，机制（即，线粒体呼吸能力和线粒体融合的变化）在两性之间是不同的。针对胎盘氧化应激的治疗策略可以改善复杂妊娠中的胎盘线粒体功能。