1090 Lipopolysaccharide exposure in swine alters ovarian toll-like receptor 4 expression

Abstract

Heat stress (HS) is associated with decreased fertility and endotoxemia as evidenced by increased systemic lipopolysaccharide (LPS) arising from decreased intestinal integrity. Across multiple species, LPS is associated with reduced female fecundity; phenotypic responses similar to HS-induced infertility, including spontaneous abortion and increased wean-to-estrus interval length. LPS binds to toll-like receptor 4 (TLR4), a membrane bound receptor, to initiate a signaling cascade culminating in the phosphorylation of nuclear factor kappa-B (pNFκB) and pro-inflammatory cytokine production. Acyloxyacyl hydrolase (AOAH) participates in LPS detoxification by cleaving the lipid A moiety, rendering the deacylated LPS unable to effectively bind TLR4. We hypothesized that endotoxemia could impact ovarian function in swine. Post-pubertal gilts were synchronized to the follicular phase of their estrous cycle using Matrix® administered orally for 14 d. Immediately following Matrix® removal, gilts were treated with vehicle control (CT; 3 mL sterile saline; n = 6) or LPS (0.1 μg/kg BW; E. coli 055:B5; n = 6) via jugular catheter four times daily (0000, 0600, 1200, 1800 h) for 5 d during the follicular phase preceding estrus. Six hours after the final LPS infusion, animals were euthanized and ovaries collected. Whole ovarian protein homogenates were prepared and western blotting performed to quantify abundance of TLR4 and AOAH protein. Relative to CT, ovaries from LPS treated gilts had reduced (P < 0.05) abundance of TLR4 protein. No effect (P > 0.05) of LPS infusion on AOAH abundance was observed. These data demonstrate that the ovary to be responsive to chronic, low-level LPS exposure, and that endotoxemia potentially contributes to seasonal infertility in swine. Funded by the Global Food Security Consortium.