Graduation Date

Spring 5-4-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Interdisciplinary Graduate Program in Biomedical Sciences

First Advisor

John S. Davis

Abstract

The corpus luteum is a transient endocrine gland that produces progesterone, a steroid hormone needed for pregnancy. It is a heterogenous gland containing many different cell types: small and large steroidogenic cells, endothelial cells, immune cells, and fibroblasts. At the end of a non-fecund reproductive cycle, the corpus luteum undergoes cyclic regression, a process which is divided into two processes: 1) functional regression, in which progesterone production rapidly declines and 2) structural regression, in which the tissue undergoes rapid remodeling into a fibrotic scar called a corpus albicans. Although fibroblasts are well-known for their role in tissue remodeling, very little is known about the role of fibroblasts in the bovine corpus luteum. In this study, we have isolated bovine luteal fibroblasts and treated them with factors that are elevated in luteal regression. We observed that luteal fibroblasts contribute to inflammation of the corpus luteum by release of the luteolysin prostaglandin F2α (PGF2α) in response to inflammatory cytokines. We also observed that luteal fibroblasts proliferate and produce more collagen in response to fibroblast growth factor 2 (FGF2). RNA sequencing data of bovine luteal tissue identified FGF2 to be elevated in response to PGF2α-induced regression, thereby contributing to the fibrotic phenotype of the regressed corpus luteum. This research has determined that although they are a small population in the corpus luteum, fibroblasts are responsive to growth factors and cytokines during luteal regression and that they can release factors into the luteal microenvironment that contribute to luteal demise. To study the luteal microenvironment in vitro in a way that better reflects the tissue, we have created a three-dimensional (3D) culture system utilizing primary bovine luteal cells. We have found that this system retains the appropriate cell types, is responsive to luteinizing hormone, and produces more progesterone compared to two-dimensional (2D) cultures. Therefore, we have identified a new role for fibroblasts in the corpus luteum and created a new culture system to better study the corpus luteum, which can aid in the search for therapies to improve women’s health and fertility in not just women, but also farm animals.

Comments

2024 Copyright, the authors

Download

Share

COinS