Infectious disease caused by exposure to Gram-negative bacterial endotoxin lipopolysaccharide (LPS) is recognized to suppress female fertility. However, the effect of varying low dose endotoxin exposure during distinct stages of follicle development on immune response, reproductive performance and lamb performance has yet to be elucidated. Therefore, the objective of this study was to evaluate acute phase response, mRNA abundance of inflammatory markers, reproductive performance and lamb growth characteristics of ewes challenged with subclinical doses of LPS. Rambouillet ewes (n = 36; 68.2 ± 1.1 kg; age 3 to 7 yr) stratified by body weight and age were assigned to treatment groups. Ewes received subcutaneous injections of saline (CON, n = 12), 1.5 μg/kg BW LPS (LOW, n = 12), or 3.0 μg/kg BW LPS (HIGH, n = 12) on d 5, 10, and 15 of a synchronized follicular wave. Ewes were subsequently placed with a raddle-painted ram on d 16 for a 35-d breeding season. On treatment d 5 and 15, blood samples, peripheral blood leukocytes, and rectal temperature were collected before and at regular intervals for 12 h after LPS challenge. Immune response to LPS was confirmed by increased temperature and serum cortisol concentrations on d 5 and 15. Endotoxin increased circulating plasma concentration of the acute phase protein, haptoglobin by greater than 15%, in both LPS-treated groups on d 5 and 15 at 12 h compared with control (P ≤ 0.05). Pro- and anti-inflammatory mRNA gene expression demonstrated no differences in expression for tumor necrosis factor α or peroxisome proliferator-activated receptor gamma among treatment groups (P > 0.10). Likewise, toll-like receptor 4 (TLR4), interleukin-8 (IL-8), and superoxide dismutase 2 (SOD2) expression was similar among treatment groups on d 5. However, ewes challenged with LPS on d 15 displayed greater mRNA expression for TLR4 from 2 to 6 h (P < 0.05), a 7-fold increase for IL-8 from 1.5 to 2.5 h (P < 0.05), and 8-fold induction for SOD2 from 2 to 6 h (P < 0.05) as compared with controls. First service conception rates were 90% for control ewes and 75% for both treated groups (P = 0.84). Treated ewes demonstrated a reduction in lamb birth weight compared with controls (P ≤ 0.05) and a tendency for reduction of 60-d adjusted weaning weight (P = 0.09). Data suggest that subacute endotoxin exposure aligning with key follicle and oocyte maturation events results in detrimental growth performance of the subsequent lamb.

中文翻译：

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反复脂多糖内毒素攻击对种母羊免疫反应和随后的羔羊生产性能的影响


暴露于革兰氏阴性细菌内毒素脂多糖 （LPS） 引起的传染病被认为会抑制女性的生育能力。然而，在卵泡发育的不同阶段改变低剂量内毒素暴露对免疫反应、繁殖性能和羔羊生产性能的影响尚未阐明。因此，本研究的目的是评估亚临床剂量 LPS 攻击的母羊的急性期反应、炎症标志物的 mRNA 丰度、繁殖性能和羔羊生长特性。按体重和年龄分层的朗布依埃母羊（n = 36;68.2 ± 1.1 kg;年龄 3 至 7 岁）被分配到处理组。母羊在同步卵泡波的第 5 天、第 10 天和第 15 天接受皮下注射生理盐水 （CON，n = 12）、1.5 μg/kg BW LPS （LOW，n = 12） 或 3.0 μg/kg BW LPS （HIGH，n = 12）。随后，母羊在 16 日与胎盘彩绘的公羊一起进行 35 天的繁殖季节。在处理第 5 天和第 15 天，在 LPS 攻击前 12 小时之前和定期收集血样、外周血白细胞和直肠温度。第 5 天和第 15 天温度和血清皮质醇浓度升高证实了对 LPS 的免疫反应。与对照组相比，在第 5 天和第 15 天，LPS 处理组在 12 小时时内毒素使急性期蛋白结合珠蛋白的循环血浆浓度增加了 15% 以上 （P ≤ 0.05）。促炎和抗炎 mRNA 基因表达显示治疗组间肿瘤坏死因子 α 或过氧化物酶体增殖物激活受体 γ 的表达无差异 （P > 0.10）。同样，第 5 天治疗组之间的 toll 样受体 4 （TLR4 ）、白细胞介素 8 （IL-8） 和超氧化物歧化酶 2 （SOD2） 表达相似。 然而，与对照组相比，第 15 天 LPS 攻击的母羊在 2 至 6 小时表现出更高的 TLR4 mRNA 表达 （P < 0.05），从 1.5 到 2.5 小时，IL-8 增加 7 倍 （P < 0.05），在 2 至 6 小时诱导 SOD2 8 倍 （P < 0.05）。对照母羊的首次服务受孕率为 90%，两个治疗组的首次服务受孕率为 75% （P = 0.84）。与对照组相比，经处理的母羊羔出生体重降低 （P ≤ 0.05） 和调整后断奶体重减少 60 天的趋势 （P = 0.09）。数据表明，亚急性内毒素暴露与关键卵泡和卵母细胞成熟事件一致，会导致后续羔羊的生长性能受到不利影响。