Changes of febrile response and placental pathological inflammation in pregnant rats after intrauterine infection in late gestation

Abstract

Objective To explore the febrile response and placental pathological inflammation of pregnant rats exposed to intrauterine infection in late gestation. Methods Pregnant Sprague–Dawley rats at gestational day 18 were randomly divided into control group and intrauterine–infected group with six rats in each. The intrauterine–infected group was intraperitoneally injected with 350 μg/kg lipopolysaccharide to establish a rat model of intrauterine infection, while the control group was injected with sterile saline of the same dose. Core temperature was measured every 1 h after intraperitoneal injection of lipopolysaccharide or saline for 8 h. At gestational day 19, after anesthesia, the placentas were taken and stained with HE. The expression levels of tumor necrosis factor–α, interleukin–6, and interleukin–1β in the placenta were determined by enzyme linked immunosorbent assay. Student t test was used for statistical analysis. Results (1) There was no temperature difference between the two groups before experimental treatment (P>0.05). Core temperature was increased 1 h after the lipopolysaccharide injection, reaching (37.67±0.08) ℃. The increase of temperature was significant compared with the control group [(37.13±0.08) ℃, t=10.178, P<0.01] . Fever was lowered 2 h later and the rats became hypothermic with body temperature below 37 ℃ in the intrauterine–infected group. The body temperature in the intrauterine–infected group after 2–6 h was (37.70±0.10), (37.23±0.05), (36.57±0.06), (36.60±0.10) and (36.57±0.08) ℃, respectively, compared with the control group [(36.83±0.12), (36.63±0.12), (36.71±0.07), (36.87±0.12), and (36.77±0.08) ℃, respectively], the differences being all statistically significant (t=11.402, 11.163, –4.025, –4.000 and –4.243, all P<0.01). (2) HE staining revealed large amounts of neutrophils infiltration, vascular enlargement and congestion in the placenta of the intrauterine–infected rats. No inflammatory cell infiltration was observed in the control placentas. (3) The expression levels of proinflammatory cytokine tumor necrosis factor–α [(0.62±0.02) ng/g], interleukin–6 [(66.12±5.11) ng/g], and interleukin–1β [(7.09±1.23) ng/g] in the intrauterine–infected group were higher than those in the control group [(0.27±0.01), (16.71±1.55) and (2.86±0.38) ng/g, respectively]. The differences were all statistically significant (t=–26.608, –18.749 and –5.714, all P<0.01). Conclusion After exposure to lipopolysaccharide in late gestation, pregnant rats show significant inflammatory response in the placenta, with suppression of febrile response and presence of hypothermia. Key words: Pregnancy complications, infectious; Fever; Hypothermia; Placenta; Cytokines; Pregnancy trimester, third; Lipopolysaccharides; Disease models, animal