Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Pathology and Laboratory Medicine

Collaborative Specialization

Developmental Biology

Supervisor

Kiser, Patti K.

2nd Supervisor

Regnault, Timothy R.H.

Co-Supervisor

Abstract

Independent of body mass index (BMI), a “Western Diet” (WD) high in refined sugars and saturated fats contributes to poor metabolic health. Maternal WD is associated with adverse pregnancy outcomes—including altered placental development. A scoping review revealed a literature gap in lifelong WD studies using non-obese animal models. To elucidate the BMI-independent effects of WD on fetoplacental development, we utilized a non-obese WD guinea pig pregnancy model. We hypothesized that maternal WD would alter placental metabolomics in conjunction with impaired placental vascularization. Multivariate analysis revealed 98 differentially abundant metabolites between WD and control placentae, with 3 commonly down at both mid- and late-gestation: stearidonic acid, 9-cis-retinoic acid, and geranic acid. Pathway analysis showed altered arachidonic acid and linoleic acid metabolism. WD pregnancies exhibited decreased fetal-placental weight ratios with a compensatory increase in maternal blood space. Our work highlights the importance of maternal diet and metabolic health independent of BMI.

Summary for Lay Audience

The modern pandemics of metabolic dysfunction and obesity are driven by our “Westernized” diets (WD)—high in processed sugars and saturated fats. While WD is historically associated with high body mass index (BMI), there is mounting evidence that WD consumption directly impacts metabolic health. For example, ~20% of normal-weight individuals are metabolically unhealthy, with WD a contributing factor. Pre-pregnancy metabolic health is a key determinant in a successful pregnancy, yet little is known about the pregnancy risks of maternal WD.

This study sought to investigate the impact of maternal WD on placental development, and we used a non-obese guinea pig model of pregnancy to specifically examine diet-related effects independent of BMI. The study diets were maintained from weaning and throughout pregnancy. Our control group received a “Mediterranean” style diet with complex carbohydrates and polyunsaturated fatty acids, while the WD group received a high-fat and high-sugar diet. Maternal weights remained unchanged, but WD sows had fatty livers. We found the placentae of WD pregnancies were inefficient, with enlarged maternal blood spaces but smaller than normal fetuses. These changes were associated with enriched omega-6 metabolite pathways in WD placentae. WD fetuses also had fatty livers, predisposing them to future poor metabolic health.

In summary, WD consumption before and during pregnancy may adversely affect a mother’s metabolic health. This can lead to adverse consequences for the development and growth of the placenta and fetus. Our findings show that efforts should be placed on pre-pregnancy optimization of maternal health to promote a healthy life-course for offspring. Therefore, our work links to the United Nations Sustainable Development Goals 3.1 and 3.4: to reduce noncommunicable disease and maternal mortality. Achieving these goals will require concerted efforts to reform current dietary habits and perspectives on metabolic health. It is our hope that health policy and education will shift focus to the roots of metabolic health, such as dietary factors, which transcend categories of BMI. Ultimately, our work highlights the roles that maternal diet and metabolic health play in placental development—with lasting consequences for the life-course trajectories of future generations.

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Available for download on Thursday, May 01, 2025

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