Department of Cell, Developmental & Cancer Biology, Graduate Program in Molecular & Cellular Biosciences, Oregon Health & Science University School of Medicine, Portland, Oregon, USA.
Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon, USA.
JCI Insight. 2021 Feb 22;6(4):138312. doi: 10.1172/jci.insight.138312.
A maternal Western-style diet (WSD) is associated with poor reproductive outcomes, but whether this is from the diet itself or underlying metabolic dysfunction is unknown. Here, we performed a longitudinal study using regularly cycling female rhesus macaques (n = 10) that underwent 2 consecutive in vitro fertilization (IVF) cycles, one while consuming a low-fat diet and another 6-8 months after consuming a high-fat WSD. Metabolic data were collected from the females prior to each IVF cycle. Follicular fluid (FF) and oocytes were assessed for cytokine/steroid levels and IVF potential, respectively. Although transition to a WSD led to weight gain and increased body fat, no difference in insulin levels was observed. A significant decrease in IL-1RA concentration and the ratio of cortisol/cortisone was detected in FF after WSD intake. Despite an increased probability of isolating mature oocytes, a 44% reduction in blastocyst number was observed with WSD consumption, and time-lapse imaging revealed delayed mitotic timing and multipolar divisions. RNA sequencing of blastocysts demonstrated dysregulation of genes involved in RNA binding, protein channel activity, mitochondrial function and pluripotency versus cell differentiation after WSD consumption. Thus, short-term WSD consumption promotes a proinflammatory intrafollicular microenvironment that is associated with impaired preimplantation development in the absence of large-scale metabolic changes.
一种西式的母体饮食(WSD)与不良的生殖结果有关,但这是来自饮食本身还是潜在的代谢功能障碍尚不清楚。在这里,我们对 10 只定期发情的雌性恒河猴进行了一项纵向研究,这些猴子经历了两次连续的体外受精(IVF)周期,一次是在食用低脂肪饮食时,另一次是在食用高脂肪 WSD 6-8 个月后。在每次 IVF 周期之前,我们从雌性动物身上收集代谢数据。对卵泡液(FF)和卵母细胞进行细胞因子/类固醇水平和 IVF 潜力评估。尽管过渡到 WSD 导致体重增加和体脂增加,但胰岛素水平没有差异。在 WSD 摄入后,FF 中的 IL-1RA 浓度和皮质醇/可的松比值显著下降。尽管成熟卵母细胞的分离概率增加,但 WSD 消耗后囊胚数量减少了 44%,时差成像显示有丝分裂时间延迟和多极分裂。囊胚的 RNA 测序表明,WSD 消耗后与 RNA 结合、蛋白通道活性、线粒体功能和多能性与细胞分化相关的基因失调。因此,短期 WSD 消耗会促进卵泡内的促炎微环境,而在没有大规模代谢变化的情况下,与植入前发育受损有关。