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Reproductive performance in cattle is influenced by many factors, including genetics, environment, nutrition, and overall physiological health. The immune system plays a critical role in this as well. Chronic, low-grade inflammation may influence fertility in cattle. In this study, we identify a population of cows within the UNL physiology herd that have increased circulating concentrations of TNFa (High-TNFa), a pro-inflammatory cytokine. Cow classified as High TNFa also had elevated concentrations of pro-inflammatory cytokines compared to Control cows, indicating a systemic inflammatory response. The objective of the study was to evaluate how systemic inflammation may contribute to metabolic disorders, such as insulin resistance, and ovarian function in cattle. While there were no differences in glucose and insulin levels between Control and High TNFa cows, concentrations of androstenedione (A4) were significantly decreased in the follicular fluid of small and large follicles. Additionally, mature cows classified as High TNFa tended to have delayed attainment of puberty and decreased reproductive performance. Cows in this study that were not cycling at the time of first breeding had increased insulin:glucose ratio, compared to cows that cycled, suggesting decreased insulin sensitivity. Together, these results indicate that cows with delayed attainment of puberty may be more susceptible to environment factors that may contribute to chronic, low-grade inflammation later in life. Collectively, these factors could be contributing to altered ovarian androgen synthesis and decreased fertility in cattle. Future studies will focus on determining the effect of systemic inflammation on ovarian somatic cell immune and steroidogenic function. Advisor: Jennifer R. Wood

Abstract: Pig follicle development is a complex but poorly understood process involving both gonadotrophins and local ovarian factors. A series of studies sought to investigate these intrafollicular cell-to-cell interactions. Microarray analysis combined with gene ontology revealed that the oocyte, granulosa and theca cells each expressed more than 650 potential secreted factors and receptors, including members of the TGF-β, IGF1, EGF and FGF families. Using a well-defined in vivo experimental paradigm that generates follicles and oocytes of different quality, the temporal expression of several growth factors in the oocyte, granulosa and theca cells collected from sows during the recruitment and mid-selection phases, as well as the final selection of the preovulatory follicle population before and after the LH surge was studied. IGF1 expression patterns indicated its potential for modulating granulosa and theca cell function during the selection stages, and an involvement in creating differences in follicular quality between the first and second preovulatory wave post-weaning. Transient up-regulation of AREG and EREG mRNA around the LH surge, suggested their involvement in ovulation. Results of a second study investigating TGF-β superfamily expression, suggested a role for GDF9 in follicle selection through the up-regulation of TGFBR1 expression, while BMP15 could be involved in ovulation through the up-regulation of BMPR1B. Expression of angiogenesis-related genes during follicle development was also investigated. During mid-selection, ANGPT2 may allow VEGFA and similar factors to stimulate vascular development or destabilize the vasculature and cause follicular atresia, while ANGPT1 may be required in the preovulatory follicle population. Associations among the transcription factor HIF1A, VEGFA and ANGPT1, suggested interactions between the ligands in regulation of angiogenesis. Finally, the effects of the pig oocyte on cumulus cell function was assessed by co-culturing cumulus cell complexes with or without denuded oocytes isolated from large oestrogenic follicles. Presence of oocytes decreased FSHR and increased HSD3B expression, potentially stimulating progesterone while attenuating oestradiol production. In conclusion, oocytes were shown to control cumulus cell function in a way that reflects their specific environment and further evidence was obtained for a complex network of growth factors and receptors in the follicle and their involvement in regulation of pig follicle development.