Author ORCID Identifier
Document Type
Dissertation
Date of Award
2025
Degree Name
Doctor of Philosophy (PhD)
Department
Basic Biomedical Science
First Advisor
Michelle L Baack, Pilar de la Puente
Abstract
The typical American diet exceeds dietary fat recommendations, contributing to the rising rates of obesity. This negatively impacts fertility, pregnancy and fetal growth, and lifelong offspring health. During pregnancy, this also increases risk of co-morbidities like gestational diabetes. Despite this, lipids are not screened during pregnancy and limited research exists evaluating these co-exposures on offspring health. Our lab used a rat model of maternal high fat (HF) diet with late-gestation diabetes (DM) to demonstrate that mitochondrial dysfunction and oxidative stress incite lifelong cardiometabolic disease risk in offspring. To determine the timing of damage, we hypothesized that maternal overnutrition incites mitochondrial dysfunction, oxidative stress, and transcriptomic dysregulation at the preimplantation embryo to impact reproduction and embryonic development for not only one, but multiple generations. Additionally, periconceptual reduction of dietary fat with Coenzyme Q10 supplementation (HF-S,CoQ) will mitigate consequences. F0 HF+DM dams were used to produce F1 embryos, then F1 and F2 dam offspring were fed control diet and grown to produce F2 and F3 embryos. HF diet mediated subfertility in F0 dams. The F1 embryo, which was only exposed to HF, displayed mitochondrial dysfunction and oxidative stress which increased transcriptomic changes including apoptosis pathways, resulting in lowered cell number. HF+DM exposed F2 embryos also displayed mitochondrial dysfunction and oxidative stress. However, there was an increase in epigenetic and cell fate pathways and higher cell number, consistent with advanced ageing. HF+DM exposed F3 embryos, which had no direct exposure, demonstrated a transcriptomic response to damage including an increased mitochondria abundance and lower oxidative stress. However, this was accompanied by a lower cell number, suggesting delayed maturation or increased cellular senescence. HF-S,CoQ in the F0 dam rescued subfertility. Mitochondrial function and oxidative stress improved in the F1 embryo; however, apoptosis pathways and low cell number persisted. Overall, this dissertation demonstrates the impact of a high fat diet and diabetes exposure on the preimplantation embryo, which can be seen across three generations. Ongoing work is investigating lifelong offspring health as well as dietary interventions during pregnancy to determine the best approach to improve generational health related to the obesity epidemic.
Subject Categories
Biology | Genetics
Keywords
Embryo Generational Mitochondria Overnutrition Oxidative stress Reproduction
Number of Pages
259
Publisher
University of South Dakota
Recommended Citation
Klein, Abigail, "Periconceptual Nutrition and the Preimplantation Embryo: Approaches for Intervention and Generational Health" (2025). Dissertations and Theses. 384.
https://red.library.usd.edu/diss-thesis/384