Maternal High-Fat Diet Consumption and Chronic Hyperandrogenemia Are Associated With Placental Dysfunction in Female...

Area of Science:

• Reproductive Endocrinology
• Maternal-Fetal Medicine
• Nutritional Science

Background:

• Polycystic ovary syndrome (PCOS) phenotypes, specifically hyperandrogenic and nonhyperandrogenic, may influence perinatal outcomes.
• Maternal obesity and diet are potential modulators of PCOS-related adverse perinatal outcomes.
• The independent and combined effects of maternal hyperandrogenism and nutritional status on placental dysfunction remain unclear.

Purpose of the Study:

• To investigate the relative contributions of maternal hyperandrogenism and diet to placental dysfunction.
• To analyze the impact of testosterone (T) and a Western-style diet (WSD) on placental blood flow, architecture, and molecular markers in a primate model.

Main Methods:

• Female rhesus macaques were assigned to four groups: control (cholesterol implants, standard diet), T implants (normal diet), WSD (cholesterol implants), or combined T and WSD.
• Placental blood flow was assessed using contrast-enhanced and Doppler ultrasound during pregnancy.
• Placental architecture was evaluated via stereological analysis, and placental growth factors, nutrient sensors, and angiogenic markers were quantified.

Main Results:

• WSD consumption increased placental flux rate by 30%.
• Both T and WSD independently increased villous volume; T decreased fetal capillary volume by approximately 40%.
• T treatment elevated mTOR and SOCS3 expression, while WSD decreased GLUT1 expression and microvillous membrane localization.

Conclusions:

• Both hyperandrogenemic and nonhyperandrogenemic phenotypes, influenced by diet, are associated with altered placental angiogenesis, nutrient sensing, and glucose transport.
• Testosterone and WSD exert distinct effects on placental vascular impedance and capillary angiogenesis, potentially impacting fetal development and perinatal outcomes.