Impact of endotoxemia on ovarian signaling and function

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Dickson, Mackenzie
Major Professor
Lance H. Baumgard
Aileen F. Keating
Committee Member
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The ovary is the female reproductive organ responsible for producing gametes and sex steroid hormones. There are many stages throughout the estrous cycle at which perturbations could affect quality of the oocyte. Heat stress (HS) is detrimental to fertility, and swine are inherently susceptible due to lack of functional sweat glands. During times of HS, blood flow is redirected to the periphery, creating a hypoxic environment within the gastrointestinal tract, culminating in compromised intestinal integrity and the influx of lipopolysaccharide (LPS) into circulation. This influx of LPS into circulation is known as endotoxemia and can arise from a myriad of physiological states, such as HS, and off-feed events, as well as obesity, diabetes, and alcoholism. Alterations to follicular growth and development incurred during endotoxemia could delay or inhibit ovulation of a viable oocyte, thus compromising potential future embryos. We hypothesized that the ovary is responsive to circulating LPS and that endotoxemia upregulates toll-like receptor 4 (TLR4) pathways, as well disrupt insulin signaling and steroidogenesis in the ovary. To test this central hypothesis, various animal models; pre- and post-pubertal gilts, as well as lactating cows, were exposed to HS and/or LPS to perturb intestinal integrity and/or mimic chronic endotoxemia. We analyzed mRNA and protein abundance in hepatic and ovarian tissue via qRT-PCR, western blotting, and immunohistochemistry, as well as quantification of insulin and LPS-binding protein, 17β-estradiol, and progesterone via ELISAs. Overall, our data demonstrates that the TLR4 pathway is activated by endotoxin in both gilts and lactating cows, and could be partially culpable for infertility that arises as a consequence of HS or infection. Interestingly, lactating cows become tolerant to exponentially increasing exposures to LPS in terms of dominant follicular growth and development. Taken together, our discoveries further delineate effects of LPS on ovarian signaling and function. These alterations, or lack thereof, are important to understand in order to facilitate development of mitigation strategies to ameliorate infertility in the future.

Sun Jan 01 00:00:00 UTC 2017