Maternal Obesity is Associated with Altered Regulation of Placental Development

Authors

• Petra A. Rose, University of Nebraska-LincolnFollow

First Advisor

Jennifer R. Wood

Committee Members

Andrea Cupp, Lynda Harris

Date of this Version

5-2026

Document Type

Thesis

Citation

A thesis presented to the faculty of the Graduate College at the University of Nebraska in partial fulfillment of requirements for the degree of Master of Science

Major: Animal Science

Under the supervision of Professor Jennifer R. Wood

Lincoln, Nebraska, May 2026

Comments

Copyright 2026, Petra A. Rose. Used by permission

Abstract

Maternal obesity is a global epidemic with increasing prevalence starting during peak reproductive years. It is strongly associated with pregnancy complications such as intrauterine growth restriction, miscarriage, and preeclampsia, many of which stem from impaired placenta development. Preeclampsia, in particular, is characterized by inefficient spiral artery remodelling and poor placenta perfusion as a consequence of reduced trophoblast (TE) migration and invasion. However, the mechanisms underlying this impaired TE essential function remain unclear. To identify placenta gene pathways disrupted by an obesogenic environment, we analyzed existing RNA-sequencing data which identified a cluster of transcription factors associated with epithelial-mesenchymal transition (EMT) that were decreased in mid-gestation placentas from obese compared to lean mouse dams. Using a diet-induced maternal obesity model, we microdissected mid-gestation e12.5 placentas into the labyrinth (LAB) and junctional zone (JNC), extracted RNA, and performed quantitative real-time PCR (qPCR) to validate the differential expression of EMT-associated transcription factors. Most EMT-associated genes were specifically downregulated in the JNC, the region enriched with invasive TE populations, but remained unchanged in the LAB. These data suggest that maternal obesity restricts EMT progression and thereby limits TE invasive capacity. To explore potential regulatory mechanisms, we examined the role of N6-methyladenosine (m6A), a predominate post-transcriptional RNA modification in mammals. Human trophoblast-like JAR cells were treated with inhibitors of the m6A methyltransferase complex (STM2457) or the demethylase complex (FB23-2) for 24 hours and performed immunofluorescence, qPCR, and western blot analysis. Inhibition of methylation (STM2457) increased RNA and protein abundance of EMT markers, whereas inhibition of demethylation (FB23-2) decreased protein abundance indicating that m6A either directly or indirectly regulates EMT gene expression in TE cells. Although, immunofluorescence showed no significant changes in structural EMT proteins E-cadherin or Vimentin at this time point. Collectively, our data indicated EMT is a tightly regulated process disrupted by maternal obesity and regulated, in part, through m6A mediated mechanisms. Understanding how obesogenic environments alter placental developmental pathways is critical for developing therapeutic strategies to reduce adverse outcomes like preeclampsia.

Advisor: Jennifer R. Wood