Date of Award
Master of Science
Aileen F. Keating
The ovary is responsible for production of steroid hormones and gametes in the female. It is endowed with a finite pool of primordial follicles, established in utero, that serve as the source of oocytes during a female’s reproductive lifespan. Alterations to ovarian function and signaling can result in disruptions to steroid hormone production, follicle activation, and oocyte quality. The degree of disruption is dependent on the developmental or estrous cycle stage of the animal as well as the duration of the perturbation. Inflammation can have deleterious effects on ovarian signaling and function, and can arise from multiple sources, such as endotoxemia, or increased levels of lipopolysaccharide (LPS) in blood. One major source of LPS is the intestine, where stresses such as hypoxia due to heat stress, high fat diets, or obesity can induce increased intestinal permeability and allow passage of LPS from the intestinal lumen into circulation. LPS signaling via its receptor, toll-like receptor 4 (TLR4), may induce inflammation in the ovary, potentially compromising oocyte and follicular quality, resulting in reduced fertility. This thesis investigated the central hypothesis that increases in circulating LPS would alter ovarian signaling and function as evidenced by activation of the TLR4, phosphatidylinositol 3 kinase (PI3K), and steroidogenic pathways. To test this hypothesis, we utilized three animal model-LPS exposure schemes in pigs: post-pubertal chronic LPS infusion, post-pubertal heat stress (HS), and pre-pubertal high fat diet (HFD). We analyzed ovarian protein and mRNA abundance via western blotting and qRT-PCR, as well as quantification of 17β-estradiol, progesterone, and LPS binding protein concentrations via ELISAs. Overall, our findings demonstrate that the ovary is responsive to LPS as demonstrated by increased ovarian TLR4 in an LPS infusion but not HFD model. We also discovered alterations to the PI3K and steroidogenic pathways in our HFD model not seen with the other exposure paradigms, indicating a potential effect of developmental age or an alternate effector mechanism in these pigs. Taken together, these data demonstrate the alterations in ovarian function due to different exposures to LPS in isolation or combination with other physiological changes. This understanding is vital to the development of amelioration strategies to reduce infertility.
Katie Lee Bidne
Bidne, Katie Lee, "Investigating the ovarian response to endotoxemia" (2017). Graduate Theses and Dissertations. 16506.