Spray-dried plasma attenuates inflammation and lethargic behaviors of pregnant mice caused by lipopolysaccharide

Abstract

This study evaluated whether dietary spray-dried plasma (SDP) can ameliorate inflammation, lethargic behaviors, and impairment of reproduction caused by lipopolysaccharide (LPS) challenge during late pregnancy. Two experiments were conducted with 125 mated female mice (C57BL/6 strain) in each experiment. All mice were shipped from a vendor on the gestation day (GD) 1 and arrived at the laboratory on GD 3. Mice were randomly assigned to dietary treatments with or without 8% SDP in the diet. On GD 17, mice determined pregnant by BW and abdomen shape were randomly assigned to intraperitoneal injections with or without 2 μg LPS. In experiment 1, 17 mice (26.7 ± 1.7 g BW) were identified pregnant and euthanized 6 h after the LPS challenge to measure inflammatory responses in uterus and placenta. In experiment 2, 44 mice (26.0 ± 1.6 g BW) were identified pregnant and euthanized 24 h after the LPS challenge to assess behavior and late-term pregnancy loss. Growth performance and reproductive responses, such as loss of pregnancy, percentage of fetal death, and etc., were measured in all pregnant mice. The LPS challenge increased (P < 0.05) uterine and placental tumor necrosis factor-α and interferon-γ, late-term pregnancy loss, and lethargy score, and decreased (P < 0.05) uterine transforming growth factor-β1, moving time and number of rearing, and growth and feed intake. The SDP decreased (P < 0.05) concentrations of both pro-inflammatory and anti-inflammatory cytokines in one or both tissues, and the lethargy score, and increased (P < 0.05) moving time and number of rearing, growth of pregnant mice, and fetal weight. However, the SDP did not affect late-term pregnancy loss caused by the LPS challenge. Consequently, dietary SDP attenuated acute inflammation and lethargic behaviors of pregnant mice caused by the LPS challenge, but did not affect late-term pregnancy loss after the acute inflammation.

Fig 1

Pro-inflammatory (A and B) and anti-inflammatory (C and D) cytokines in gestational tissues of pregnant mice as affected by dietary SDP and LPS challenge. Values are means ± SE, n = 3, 4, 5, and 5 for CON-PBS (control diet + intraperitoneal injection of phosphate-buffered saline on GD 17), CON-LPS (control diet + intraperitoneal injection of lipopolysaccharides on GD 17), SDP-PBS (8% spray-dried plasma diet + intraperitoneal injection of phosphate-buffered saline on GD 17), and SDP-LPS (8% spray-dried plasma diet + intraperitoneal injection of lipopolysaccharide on GD 17), respectively. D, diet; L, LPS; D × L, interaction between diet and LPS. *Different from CON within a challenge treatment, P < 0.05.

Fig 2. Behaviors of pregnant mice under acute inflammation by LPS challenge during 5 min.

Values are means ± SE, n = 3, 4, 13, and 10 for CON-PBS (control diet + intraperitoneal injection of phosphate-buffered saline on GD 17), CON-LPS (control diet + intraperitoneal injection of lipopolysaccharides on GD 17), SDP-PBS (8% spray-dried plasma diet + intraperitoneal injection of phosphate-buffered saline on GD 17), and SDP-LPS (8% spray-dried plasma diet + intraperitoneal injection of lipopolysaccharide on GD 17), respectively. (A) Moving time, (B) Number of rearing, (C) Lethargy score (0 = normal activity, 1 = slightly reduced exploration, 2 = reduced exploration with short intervals without activity, 3 = longer intervals without activity, 4 = strongly reduced activity and huddling, 5 = huddling and lethargy but reaction to environmental stimulus, and 6 = no reaction to environmental stimulus). D, diet; L, LPS; T, time; D × L, interaction between diet and LPS; D × T, interaction between diet and time; L × T, interaction between LPS and time; D × L × T, interaction among diet, LPS, and time. *Different from CON within a challenge treatment at each time point, P < 0.05.