Bacterial contamination of the female genital tract after parturition is common and subsequent infections are associated with infertility. Infections of the uterus or mammary gland in cattle perturb ovarian function, with decreased dominant follicle growth rate and delayed ovulation. Granulosa cells that line ovarian follicles express the molecular machinery necessary to respond to common bacterial pathogen-associated molecular patterns (PAMPs), suggesting that granulosa cells may play a role in ovarian innate immunity. In the present thesis, the effect of bacterial PAMPs on ovarian follicle cells was examined during follicular growth, from emergence through dominance, and the early stages of embryogenesis. Granulosa cells from emerged or dominant bovine follicles increased production of inflammatory mediators, such as IL-6 and IL-8, through Toll-like receptor (TLR)-dependent pathways in response to the PAMPs lipopolysaccharide and the synthetic triacylated lipopeptide Pam3CSK4. The requirement for TLR2 and TLR4 was confirmed by using siRNA, showing activation of MAPK intracellular pathways and inhibiting key signals (p38, MEK or NFkB) in TLR pathways. The endocrine function of granulosa cells was perturbed by PAMPs, with decreased oestradiol and progesterone output. In addition, the endocrine environment affected granulosa cellular responses, with high EGF increasing the cellular response to PAMPs. Bacterial PAMPs also perturbed the oocyte, with increased cumulus expansion and parthenote cleavage rate, as well as changes in key genes involved in oocyte maturation. Finally, a human granulosa cell line was used to examine if PAMPs perturb human as well as bovine ovarian health. Indeed, human cells also expressed TLRs and mounted a cellular response to PAMPs at the mRNA level. This thesis provides a molecular mechanism for the perturbation of ovarian function by an infection at a site distal to the ovary.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:678500 |
| Date | January 2013 |
| Creators | Price, Jennifer Claire |
| Publisher | Swansea University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://cronfa.swan.ac.uk/Record/cronfa42833 |
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