Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center (ONPRC), Oregon Health & Science University (OHSU), Portland, OR, USA.
Department of Pathology, OHSU, Portland, OR, USA.
J Dev Orig Health Dis. 2021 Dec;12(6):908-914. doi: 10.1017/S204017442000121X. Epub 2020 Dec 14.
We previously demonstrated decreased placental perfusion, reduced amniotic fluid protein content, and increased pregnancy loss in a nonhuman primate model of gestational protein restriction. Here, our objective was to link these detrimental findings with a functional placental assessment. As blood flow is critical to maternal-fetal exchange, we hypothesized that a protein-restricted diet would impair placental taurine uptake. Pregnant rhesus macaques were maintained on either control chow (CON, n = 5), a 33% protein-restricted diet (PR33, n = 5), or a 50% PR diet (PR50, n = 5) prior to and throughout pregnancy. Animals were delivered on gestational day 135 (G135; term is G168). Taurine activity was determined in fresh placental villous explants. Taurine transporter (TauT) protein expression, placental growth factor (PLGF), and insulin-like growth factor (IGF)-1 and IGF-2 protein concentrations were measured, and histological assessment was performed. Fetal body weights and placental weights were comparable between all three groups at G135. Placental taurine uptake was decreased in PR33- and PR50-fed animals compared to CON, yet TauT expression was unchanged across groups. PLGF was significantly increased in PR50 vs. CON, with no change in IGF-1 or IGF-2 expression in placental homogenate from PR-fed animals. Accelerated villous maturation was observed in all PR50 cases, three of five PR33, and was absent in CON. We demonstrate conserved fetal growth, despite a decrease in placental taurine uptake. Increased expression of PLGF and expansion of the syncytiotrophoblast surface area in the severely protein-restricted animals suggest a compensatory mechanism by the placenta to maintain fetal growth.
我们之前在非人灵长类动物的妊娠蛋白限制模型中证明了胎盘灌注减少、羊水蛋白含量降低和妊娠丢失增加。在这里，我们的目的是将这些有害发现与功能胎盘评估联系起来。由于血液流动对母婴交换至关重要，我们假设限制蛋白的饮食会损害胎盘牛磺酸摄取。妊娠恒河猴在妊娠前和整个妊娠期间分别维持在对照饲料（CON，n = 5）、33%蛋白限制饮食（PR33，n = 5）或 50% PR 饮食（PR50，n = 5）。动物于妊娠第 135 天（G135；足月为 G168）分娩。在新鲜胎盘绒毛外植体中测定牛磺酸活性。测量胎盘生长因子（PLGF）和胰岛素样生长因子（IGF-1 和 IGF-2）蛋白浓度，并进行组织学评估。在 G135 时，所有三组的胎儿体重和胎盘重量均无差异。与 CON 相比，PR33 和 PR50 喂养的动物胎盘牛磺酸摄取减少，但 TauT 表达在各组之间不变。与 CON 相比，PR50 中的 PLGF 显著增加，而 PR 喂养动物的胎盘匀浆中 IGF-1 或 IGF-2 表达无变化。在所有 PR50 病例中均观察到绒毛加速成熟，PR33 的五例中有三例，而 CON 中没有。我们证明了尽管胎盘牛磺酸摄取减少，但胎儿生长仍保持不变。严重限制蛋白的动物中 PLGF 的表达增加和合体滋养层表面积的扩大表明胎盘存在一种代偿机制来维持胎儿生长。
