Date of Award

Spring 5-6-2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Biochemistry & Molecular Biology

First Advisor

John S. Davis

Abstract

This dissertation describes a study of the mechanisms regulating the genesis and subsequent involution of the temporary endocrine structure, the corpus luteum (CL), through the use of a bovine model. The CL is essential for maintaining a suitable uterine environment for embryo implantation and early development through secretion of the steroid hormone progesterone. The “Rise and Fall” of the CL occurs within each estrous cycle whereby the CL must form from the ruptured follicle, secrete sufficient progesterone for uterine maturation, and at the end of the cycle (or pregnancy) regress to allow new follicular development. During the rise of the CL, the composition and regulation of lipid droplets (LDs) were studied and it was determined that LDs are a common luteal cell structure formed by day 3 post-ovulation, and store both cholesteryl esters and triglycerides. Additionally, the LD-associated proteome was examined and established that steroidogenic enzymes are enriched in purified LD fractions. Demonstrating that luteal LDs may serve as critical mediators of steroidogenesis by storing steroid precursors in close association with steroidogenic enzymes. At the fall of the CL, alterations in the luteal transcriptome revealed changes consistent with early activation of cytokine signaling. One such cytokine, C-X-C motif chemokine ligand 8 (previously IL-8), was assessed for its ability to regulate luteal cell function. CXCL8 expression was determined to be induced in bovine luteal cells via p38 and JNK signaling and could induce bovine neutrophil migration. However, neutrophils had no effect on progesterone secretion unlike activated peripheral blood mononuclear cells which could inhibit luteal cell progesterone secretion. In total, the studies described herein indicate that both LDs and cytokines play important roles in CL development, function, and regression.

2016.11.14 Intro Chapter Permissions.pdf (160 kB)
Springer License

2016.08.18 IL8 paper permissions.pdf (86 kB)
Bioscientifica License

Available for download on Wednesday, October 25, 2017

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