Maternal High-Fat Diet Consumption and Chronic Hyperandrogenemia Are Associated with Placental Dysfunction in Female Rhesus Macaques

Kelly Kuo, Victoria H.J. Roberts, Jessica Gaffney, Diana L. Takahashi, Terry Morgan, Jamie O. Lo, Richard L. Stouffer, Antonio E. Frias

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


The risk of adverse perinatal outcomes with maternal polycystic ovary syndrome may differ among hyperandrogenic and nonhyperandrogenic phenotypes and is likely modulated by maternal obesity and diet. The relative contribution of maternal hyperandrogenism and nutritional status to placental dysfunction is unknown. Female rhesus macaques (N = 39) were assigned at puberty to one of four treatment groups: subcutaneous cholesterol implants and a standard chow diet (controls); testosterone (T) implants and a normal diet; cholesterol implants and a high-fat, Western-style diet (WSD); and testosterone implants in combination with a high-fat diet. After 3.5 years of treatment, contrast-enhanced and Doppler ultrasound analyses of placental blood flow were performed for a representative subset of animals from each treatment group during pregnancy, and placental architecture assessed with stereological analysis. Placental growth factors, cellular nutrient sensors, and angiogenic markers were measured with ELISA and Western blotting. WSD consumption was associated with a 30% increase in placental flux rate relative to that in animals receiving a normal diet. T and WSD treatments were each independently associated with increased villous volume, and T also was associated with an ∼40% decrease fetal capillary volume on stereological analysis. T treatment was associated with significantly increased mTOR and SOCS3 expression. WSD consumption was associated with decreased GLUT1 expression and microvillous membrane localization. Hyperandrogenemic and nonhyperandrogenemic phenotypes are associated with altered placental angiogenesis, nutrient sensing, and glucose transport. WSD and T appear to have distinct effects on vascular impedance and capillary angiogenesis.

Original languageEnglish (US)
Article number201900149
Pages (from-to)1937-1949
Number of pages13
Issue number8
StatePublished - Jul 4 2019

ASJC Scopus subject areas

  • Endocrinology


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