Roberts Victoria H J, Lo Jamie O, Lewandowski Katherine S, Blundell Peter, Grove Kevin L, Kroenke Christopher D, Sullivan Elinor L, Roberts Charles T, Frias Antonio E
1 Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.
2 Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR, USA.
Reprod Sci. 2018 Jan;25(1):110-119. doi: 10.1177/1933719117704907. Epub 2017 Apr 26.
Maternal malnutrition during pregnancy impacts fetal growth, with developmental consequences that extend to later life outcomes. In underdeveloped countries, this malnutrition typically takes the form of poor dietary protein content and quality, even if adequate calories are consumed. Here, we report the establishment of a nonhuman primate model of gestational protein restriction (PR) in order to understand how placental function and pregnancy outcomes are affected by protein deficiency. Rhesus macaques were assigned to either a control diet containing 26% protein or switched to a 13% PR diet prior to conception and maintained on this PR diet throughout pregnancy. Standard fetal biometry, Doppler ultrasound of uteroplacental blood flow, ultrasound-guided amniocentesis, and contrast-enhanced ultrasound (CE-US) to assess placental perfusion were performed mid-gestation (gestational day 85 [G85] where term is G168) and in the early third trimester (G135). Our data demonstrate that a 50% reduction in dietary protein throughout gestation results in reduced placental perfusion, fetal growth restriction, and a 50% rate of pregnancy loss. In addition, we demonstrate reduced total protein content and evidence of fetal hypoxia in the amniotic fluid. This report highlights the use of CE-US for in vivo assessment of placental vascular function. The ability to detect placental dysfunction, and thus a compromised pregnancy, early in gestation, may facilitate the development of interventional strategies to optimize clinical care and improve long-term offspring outcomes, which are future areas of study in this new model.
孕期母亲营养不良会影响胎儿生长，其发育后果会延伸至日后的生活结局。在欠发达国家，这种营养不良通常表现为膳食蛋白质含量和质量不佳，即便摄入了足够的热量。在此，我们报告建立了一种妊娠期蛋白质限制（PR）的非人灵长类动物模型，以了解蛋白质缺乏如何影响胎盘功能和妊娠结局。将恒河猴分为两组，一组给予含26%蛋白质的对照饮食，另一组在受孕前改为13%的PR饮食，并在整个孕期维持该PR饮食。在妊娠中期（妊娠第85天[G85]，足月为G168）和孕晚期早期（G135）进行标准胎儿生物测量、子宫胎盘血流的多普勒超声检查、超声引导下羊膜腔穿刺术以及用于评估胎盘灌注的对比增强超声（CE-US）检查。我们的数据表明，整个孕期膳食蛋白质减少50%会导致胎盘灌注减少、胎儿生长受限以及50%的妊娠丢失率。此外，我们还发现羊水总蛋白含量降低以及胎儿缺氧的证据。本报告强调了CE-US在体内评估胎盘血管功能方面的应用。在妊娠早期检测到胎盘功能障碍以及由此导致的妊娠受损，这一能力可能有助于制定干预策略，以优化临床护理并改善后代的长期结局，而这正是这个新模型未来的研究方向。
