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Adverse Placental Perfusion and Pregnancy Outcomes in a New Nonhuman Primate Model of Gestational Protein Restriction

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Abstract

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 uter-oplacental 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.

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Author information

Authors and Affiliations

  1. Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, 505 NW 185th Ave, Beaverton, OR, 97006, USA

    Victoria H. J. Roberts PhD, Katherine S. Lewandowski BS, Charles T. Roberts Jr PhD & Antonio E. Frias MD

  2. Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR, USA

    Jamie O. Lo MD & Antonio E. Frias MD

  3. Division of Cardiometabolic Health, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA

    Peter Blundell BS, Kevin L. Grove PhD & Charles T. Roberts Jr PhD

  4. Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA

    Christopher D. Kroenke PhD & Elinor L. Sullivan PhD

  5. Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, USA

    Christopher D. Kroenke PhD

  6. Department of Biology, University of Portland, Portland, OR, USA

    Elinor L. Sullivan PhD

Authors
  1. Victoria H. J. Roberts PhD
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  2. Jamie O. Lo MD
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  3. Katherine S. Lewandowski BS
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  7. Elinor L. Sullivan PhD
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  8. Charles T. Roberts Jr PhD
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  9. Antonio E. Frias MD
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Correspondence to Victoria H. J. Roberts PhD.

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Roberts, V.H.J., Lo, J.O., Lewandowski, K.S. et al. Adverse Placental Perfusion and Pregnancy Outcomes in a New Nonhuman Primate Model of Gestational Protein Restriction. Reprod. Sci. 25, 110–119 (2018). https://doi.org/10.1177/1933719117704907

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