Highlights d Single-cell transcriptomic roadmap of NHP ovarian aging d Molecular signatures revealed for NHP oocytes at stepwise developmental stages d Cell-type-specific inactivation of antioxidant genes in aged monkey and human ovaries

ABSTRACT

Abstract-Inhibitors of angiogenic factors are known to be upregulated, and their levels increase in the maternal circulation before the onset of preeclampsia. We reproduced a previously characterized model of preeclampsia by adenoviral overexpression of the soluble vascular endothelial growth factor (VEGF) receptor sFlt-1 (also referred to as sVEGFR-1) in pregnant and nonpregnant Sprague-Dawley rats. Animals were treated with VEGF121 at 0, 100, 200, or 400 g/kg once or twice daily (nϭ8 per group; 64 total) and compared with normal control animals (nϭ4 per group) by examination of systolic blood pressure, urinary albumin and creatinine, renal histopathology, and glomerular gene expression profiling. sFlt-1 expression induced hypertension with proteinuria and glomerular endotheliosis and significant changes in gene expression. VEGF121 treatment alleviated these symptoms and reversed 125 of 268 sFlt-1-induced changes in gene expression. VEGF121 had beneficial effects in this rat model of preeclampsia without apparent harm to the fetus. Further study of VEGF121 as a potential therapeutic agent for preeclampsia is warranted.

This research suggests that aspects of the built environment are determinants of child weight status, ostensibly by influencing physical activity and dietary behaviors.