Acute TNFα exposure leads to Differential mRNA Expression and Protein Phosphorylation in Primary Follicles

Authors

Heidi B. Miller, University of Nebraska-LincolnFollow
Kelsey A. Timme, University of Nebraska-LincolnFollow
Jennifer R. Wood, University of Nebraska-LincolnFollow

Date of this Version

Spring 5-2018

Document Type

Thesis

Citation

Miller, H. B., Timme, K. A., Wood, J. R. (2018). Acute TNFα exposure leads to Differential mRNA Expression and Protein Phosphorylation in Primary Follicles.

Comments

Copyright Heidi B. Miller 2018

Abstract

Obesity is the condition of having an excessive amount of body fat, which allows several acute stressors such as TNFα and H₂O₂ to exert their function. TNFα is a cytokine released by adipose cells that is involved in cellular inflammation. H₂O₂ is a reactive oxygen species (ROS) and oxidative stressor, further contributing to cellular inflammation. The more adipose tissue present in bodies, the more oxidative stress and inflammation cells experience. In healthy individuals, cellular mechanisms are present to remove excess ROS, however, with the high proportion of adipose tissue this system is overwhelmed. This growing epidemic is affecting all ages of life from children to adults. The Center of Disease Control and Prevention (CDC) estimate that more than one third of United States adults are obese, costing the nation approximately $147 billion dollars. Additionally, childhood obesity affects nearly 17% of adolescents across the nation. This is likely due to the high fat, high sugar diets being consumed on a daily basis. In addition to several health issues, obesity can cause alternative issues for pregnant women and the fetus. According to the Mayo Clinic, obesity has the potential to decrease fertility as a result of abnormal ovulation, increase likelihood of pregnancy complications, infections, and pregnancy loss. This study addresses the hypothesis that the presence of acute stressors such as TNFα and H₂O₂ of leads to a change in the expression of oocyte-specific proteins. For this study, primary follicles will be collected from 12-day old mice and exposed to treatments of 10 pg TNFα and 0, 25, 50, and 100 μM H₂O₂,inducing acute stress. In pilot studies, this concentration of H₂O₂ increased not only the abundance of Dppa3 and Pou5f1 transcripts in the matured oocytes, but also the amount of protein synthesized from these transcripts. This study will address the role of acute stressors such as TNFα and H₂O₂ induced oxidative stress on oocyte quality and developmental competence of the oocyte. This is important because of the increased ovarian oxidative stress in obese animals and presumably women.