Abstract #T311

# T311
Effects of lipopolysaccharide (LPS)-induced inflammatory response on early embryo survival in ewes.
M. R. Graham*1, E. C. Bowdridge1, S. A. Bowdridge1, I. Holásková1, T. H. Elsasser2, R. A. Dailey1, 1West Virginia University, Morgantown, WV, 2United States Department of Agriculture-Agricultural Research Service (USDA-ARS), Beltsville Agricultural Research Center (BARC), Beltsville, MD.

The effects of proinflammatory pathway triggers on pregnancy success was assessed in early pregnant ewes. Effects of endogenous cytokine activation (via LPS), direct exogenous tumor necrosis factor-α (TNF-a) and TNF-a+Dexamethasone (TNF-a+Dex) administration were compared in regard to pregnancy rate. Dorset × Texel ewes (n = 38) were synchronized for estrus and bred to fertile rams (d 0). On d 6, ewes were assigned to receive via the jugular 2.5 mL containing either PBS (n = 9), 2.5 µg/kg LPS (n = 9), 1 µg/kg TNF-a (n = 10) at 0 and 30min, or 2.5 µg/kg of LPS after 3.5 mL containing 0.14 mg/kg BW im Dex (n = 10) at −12h and 0h. Behavioral changes and rectal temperatures (BT) were recorded before challenge and hourly for 12 h. Jugular blood was collected before challenge, every 30 min for 3 h, hourly until 12 h, at 24, 36, and 48 h, and on d 10 and d 26 for progesterone. At d 26, pregnancy was examined using ultrasonography. The proportion of ewes pregnant was analyzed by Chi-squared and Fisher’s exact test with preplanned contrasts. Other data were analyzed by repeated measures ANOVA. Treatment with LPS resulted in peak BT at 4 h (40°C; control 38°C; P < 0.05), increased lethargy, mucosal response, white blood cell (WBC) count (9.8 × 106; control 9.1 × 106; P < 0.05), serum TNF-a (0.9 ng/mL; control 0.2 ng/mL; P < 0.05). Treatment with LPS+Dex resulted in peak BT at 4 h (39°C), but was blunted by Dex. Additionally, Dex blocked mucosal and lethargic responses and attenuated LPS-induced increases in TNF-a and did not improve pregnancy rate compared with LPS alone (P > 0.05). TNF-a treatment increased BT at 1 h (39°C), did not induce lethargy; 5/10 ewes showed a mucosal response; and WBC counts did not change but high concentrations of TNF-a were not sustained. More control and TNF-a ewes (15/19) were pregnant than LPS or LPS+Dex ewes (9/19; P = 0.045). In summary, an inflammatory response was elicited by LPS and resulted in reduced proportion of ewes pregnant regardless of Dex administration. Treatment with TNF-a did not affect proportion of ewes pregnant, perhaps due to low serum TNF- a levels or different pathway components stimulated by LPS. These data show that a sustained inflammatory response to LPS decreased pregnancy rate and may involve a complex cascade of inflammatory mediators elicited by LPS.

Key Words: LPS, embryonic loss, sheep