Catalyst Awardee

Project Description

Effects of maternal obesity on oocyte aging in female offspring of the BPH/5 preeclamptic-like mouse

Jenny L. Sones, DVM, PhD, Diplomate ACT | Louisiana State University School of Veterinary Medicine; Fiona Herzog, DVM | Louisiana State University School of Veterinary Medicine
Competition Sponsor: US National Academy of Medicine
Awardee Year: 2022


The majority of adults in the United States are overweight or obese often with concurrent cardiovascular disease. The genesis of the cardiometabolic epidemic likely begins with in utero development. Hypertensive pregnancies, as in preeclampsia (PE), greatly increase offspring risk of cardiometabolic diseases later in life. The precise mechanism of this is unknown and the long-term effects on offspring are unclear. To study the transgenerational effect of PE, we utilize the obese female BPH/5 mouse which spontaneously phenocopies PE as seen in women. Our overarching hypothesis is BPH/5 oocytes have premature aging that contribute to cardiometabolic disease in offspring which can be reversed with maternal weight loss before pregnancy. Adult female BPH5 mice are obese with leptin resistance, increased blood pressure, and altered estrogen signaling before pregnancy compared to age-matched lean normotensive control mice. First, oocytes will be evaluated in a time course for signs of reactive oxygen species (ROS), mitochondrial dysfunction, and markers of aging in adult BPH/5 female mice. Our aims are designed to test if BPH/5 female weight loss via pair-feeding before conception would improve offspring cardiometabolic disease by reversing premature oocyte aging. Preliminary data supports our approach that attenuation of BPH/5 maternal obesity via weight loss reduces pregnancy hypertension and in utero fetal death. In the future, we will investigate the epigenetic and in utero programming of maternal weight loss on oocyte markers as predictors of cardiometabolic disease. The findings of this proposal are necessary to understand the effects of PE on offspring into adulthood.


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