Abstract：
Over 35% of reproductive-age women in the US are obese, putting them at increased risk for numerous obstetric complications due to abnormal labor. While the association between maternal obesity and abnormal labor has been well documented, the mechanisms responsible for this remain understudied. The uterine smooth muscle, myometrium, has high energy needs in order to fuel regular uterine contractions during parturition. However, the precise mechanisms by which the myometrium meets its energy demands has not been defined. Here, our objective was to define the effects of obesity on energy utilization in the myometrium during labor. We generated a mouse model of maternal diet-induced obesity (DIO) and found that these mice had a higher rate of dystocia than control chow-fed (CON) mice. Moreover, compared to CON mice, DIO mice at term, both before and during labor had lower in vivo spontaneous uterine contractility. Untargeted transcriptomic and metabolomic analyses suggest that DIO is associated with elevated long-chain fatty acid uptake and utilization in the uterus, but also an accumulation of medium-chain fatty acids. DIO uteri also had an increase in the abundance of long chain-specific β-oxidation enzymes, which may be responsible for the observed increase in long-chain fatty acid utilization. This altered energy substrate utilization may be a contributor to the observed contractile dysfunction.
摘要：
在美国，超过35%的育龄妇女肥胖，由于产程异常，使他们面临许多产科并发症的风险增加。虽然产妇肥胖和异常分娩之间的关联已经有了很好的记录，造成这种情况的机制仍未得到充分研究。子宫平滑肌，子宫肌层,有很高的能量需求，以便在分娩期间定期子宫收缩。然而,子宫肌层满足其能量需求的确切机制尚未确定。这里,我们的目的是明确肥胖对分娩过程中子宫肌层能量利用的影响.我们建立了母亲饮食诱导的肥胖（DIO）的小鼠模型，发现这些小鼠的难产率高于对照食物喂养（CON）小鼠。此外，与CON小鼠相比，足月DIO小鼠，分娩前和分娩期间的体内自发性子宫收缩力均较低。非靶向转录组和代谢组学分析表明，DIO与子宫中长链脂肪酸摄取和利用的升高有关。还有中链脂肪酸的积累.DIO子宫也增加了长链特异性β-氧化酶的丰度，这可能是观察到的长链脂肪酸利用率增加的原因。这种改变的能量底物利用可能是观察到的收缩功能障碍的原因。
