Placental adaptations in a nonhuman primate model of gestational protein restriction.

Jessica E. Gaffney,Victoria H.J. Roberts,Terry K. Morgan,Antonio E. Frias

doi:10.1017/s204017442000121x

Abstract

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.

Highlights

Maternal malnutrition during pregnancy adversely affects maternal health and fetal development, which may result in intrauterine growth restriction (IUGR) and may be associated with an increased risk of health complications in the offspring during adulthood.[1,2] In underdeveloped countries, malnutrition typically results from low- or poor-quality protein dietary content, leading to overall sufficient calorie intake but inadequate nutrient consumption
In a nonhuman primate (NHP) model of gestational protein restriction (PR), we previously reported the adverse effects of a 50% reduction in maternal dietary protein on pregnancy outcomes
Within the small sample size, we report a modest decrease in blood urea nitrogen (BUN) expression which is a characteristic of protein deficiency (Table 1)

Summary

Introduction

Maternal malnutrition during pregnancy adversely affects maternal health and fetal development, which may result in intrauterine growth restriction (IUGR) and may be associated with an increased risk of health complications in the offspring during adulthood.[1,2] In underdeveloped countries, malnutrition typically results from low- or poor-quality protein dietary content, leading to overall sufficient calorie intake but inadequate nutrient consumption. There was no adverse impact of PR on conception, we demonstrated an increased risk of early pregnancy loss.[3] Upon establishment of this model, maternal consumption, assessed by daily food weighing and monitoring quantified throughout, and for 2 weeks following, the transition from control to 50% protein-reduced chow, showed a maintenance of consumed calories.[4] This NHP model mimics the human scenario of reasonable total intake but significant protein deficiency. It provides the opportunity to examine the consequences of maternal malnutrition on placental nutrient transport and regulation of fetal supply and developmental cues

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