Implications of Repeated Subacute Lipopolysaccharide Exposure During Synchronized Estrous

Abstract Acute inflammation induced by chronic infection or a single intravenous administration of the bacterial endotoxin, lipopolysaccharide (LPS) induces immune responses capable of depressing female fertility. However, the effect of dose and repeated endotoxin exposure during the estrous cycle on immune response and reproductive performance has yet to be investigated. To investigate the effects of varying doses of LPS delivered at distinct stages of follicular maturation, thirty-six Ramboulliet ewes (68.2 ± 1.1 kg; age 3 to 7 yr) were stratified by weight and age and randomly assigned to vehicle (n = 12), low (n = 12) or high (n = 12) LPS-treated groups to evaluate febrile response, serum progesterone and cortisol concentrations, and reproductive performance. Ewes received subcutaneous injections of saline (CON), 1.5 µg/kg BW LPS (LOW), or 3.0 µg/kg BW LPS (HIGH) on d 5, 10, and 15 after onset of synchronized estrus. Estrous synchronization was determined by serum progesterone (P4) analysis. All ewes demonstrated similar P4 profiles, but HIGH-LPS ewes tended to have elevated values (P = 0.1). On treatment d 5 and 15, blood samples and rectal temperature were collected before and intermittently throughout the duration of the trial. Lipopolysaccharide increased rectal temperature of LOW and HIGH groups at 2, 3, and 6 h, respectively after initial LPS challenge (d 5) when compared with vehicle-treated controls (0.67, and 0.70 °C, P < 0.05), but no significance was observed at d 10 or 15. Serum concentrations of cortisol were similar among treatment groups at 0 h (P > 0.05). However, a rapid and sustained cortisol increase was demonstrated within 1 h of LPS exposure in both LPS-treatment groups compared with controls (P = 0.001). A similar pattern of cortisol release among treatment groups was demonstrated on d 15 (P < 0.05). While there was no significant difference in services per cycle by treatment, there was a marked difference (16.67%) in remarks during the second cycle for HIGH and LOW groups (P = 0.23) as compared with controls. Control ewes had d 100 pregnancy rate of 90.91%, while low and high LPS-treated groups had pregnancy rates of 91.67% (P = 0.96) and 83.33% (P = 0.59) respectively. The administration of LPS resulted in significant increases in serum cortisol in treated ewes, and serum progesterone was significantly increased in LOW LPS-treated ewes compared with CON or HIGH LPS-treated ewes. Thus, alterations of temperature, steroid hormone concentration, and time to estrus in response to LPS may ultimately implicate female fertility and prevent economic losses for producers.