Electronic Thesis and Dissertation Repository

Thesis Format



Master of Science


Physiology and Pharmacology


Regnault, Timothy RH


Both metabolic and cognitive dysfunction can originate from fetal reprogramming precipitating from adverse conditions experienced in utero. Of note is the western diet (WD), which is associated with maternal energy imbalances that may hinder fetal development through altered placental function. Brain-derived neurotrophic factor (BDNF), a growth factor that supports the placenta and developing brain, is responsive to such energy imbalances. This study sought to investigate the impact of lifelong maternal WD consumption on fetoplacental development, focusing on relations between placental changes, and fetal growth and neurodevelopment in a guinea pig model. Maternal WD consumption resulting in a lean metabolically unhealthy maternal phenotype was associated with lean fetal hepatic steatosis. Placentae of these fetuses were large yet inefficient and showed reduced BDNF expression. Similar reductions in BDNF were noted in fetal brains, coinciding with decreased cell density. Such cellular changes may convey long-term cognitive deficits, although their consequences remain unknown.

Summary for Lay Audience

Over the last century, rates of metabolic disease and mental illness have risen. While once thought to possess distinct pathologies, metabolic and cognitive dysfunction show commonalities in their etiology; both may originate from adversity experienced in utero through the process of fetal reprogramming. Adverse intrauterine conditions can lead to changes in the development of the placenta, a critical organ with diverse function that exists to support the developing fetus. Abnormal placental function translates to altered fetal development, predisposing the child to later disease. As such, optimizing the maternal environment to foster healthy placental development is critical to minimizing the child’s risk of disease. While obesity has been identified as a risk factor to fetal development, it is difficult to distinguish between detriments caused by obesity, versus the lifestyle factors which precede its development. Of note is the Western Diet (WD); rich in saturated fat and added sugar, the WD is associated with the onset of metabolic and neurological dysfunction. Despite its prevalence, little is understood about the risks associated with habitual WD consumption before and during pregnancy. This study sought to investigate how lifelong maternal WD consumption would impact the development of the placenta and fetus, focusing on fetal growth and brain development in a guinea pig model. Both maternal and fetal populations exposed to the WD developed fatty livers yet maintained lean body compositions. The placentae of these animals were oversized, inefficient, and showed significant tissue damage. In addition, these placentae showed lower levels of a growth factor essential for placental and fetal brain development. Similar reductions in the growth factor were noted in the fetal brain of those born to WD-fed mothers, which coincided with reduced brain cell density. Taken together, habitual WD consumption before and during pregnancy may convey both metabolic and neurological complications to the fetus, possibly through alterations in growth factor production. The significance of these findings is magnified by their occurrence in a “lean” model, which emphasizes that evaluating lifestyle factors such as dietary patterns in parallel with markers of maternal metabolic health is potentially more pertinent to assessing pregnancy risk than BMI alone.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.