Effects of low-grade inflammation on fetal health and pregnancy outcome in mice
Friday, February 14, 2020
4:45 PM – 5:00 PM
Location: Max Bell - MB251
Introduction: Low-grade inflammation associates with many pregnancy disorders. However, the processes affected by low-grade inflammation in pregnancy are not well understood. To gain insight into possible mechanism(s) underlying harmful low-grade inflammation, we generated a model of maternal inflammation. Specifically, we set out to test the hypothesis that exposure to low-levels of bacterial endotoxin reproduce inflammatory processes and pregnancy outcomes consistent with that of low-grade inflammation.
Methods: Syngeneic (C57BL/6 x C57BL/6) and allogeneic (C57BL/6 x DBA/2J) mouse crosses were used to test the impact of genetic similarity/dissimilarity on lipopolysaccharide (LPS) inflammation. Two LPS doses, (50 ug/Kg; n=8, 200 ug/Kg; n=8) and saline control (n=8) were administered i.p. to pregnant mice on embryonic day (E)7.5. The effects of low and high levels of LPS on systemic inflammation (WBC counts) and pregnancy outcome (fetal viability) were assessed on E9.5.
Results: High-dose LPS altered peripheral immune cell composition by elevating lymphocyte/monocyte ratios in the allogeneic cross (1.5x +/- 6.833), and elevating neutrophil/lymphocyte ratios in the both crosses (2.1x +/- 0.13, syngeneic, and 16.7x +/- 7.45, allogeneic). In contrast, exposure to low-dose LPS in the allogeneic model elevated monocyte/lymphocyte ratios (12x +/- 3.37) and lymphocyte/neutrophil ratios (466x +/- 0.26) but had no effect in the syngeneic model. Unsurprisingly, high-dose LPS resulted in fetal demise at E9.5 (100% +/- 0, syngeneic; 85.7% +/- 37, allogeneic). In syngeneic pregnancies, low-dose LPS resulted in 76% fetal demise (+/- 43), however exposure to low-dose LPS within the allogeneic background resulted in moderately lower (25% +/- 50) fetal resorption rates.
Conclusion: Low-dose LPS exposure in early pregnancy generates inflammatory readouts that are consistent with low-grade inflammation. Notably, the effects of LPS were most pronounced in syngeneic pregnancies, suggesting that lowered heterogeneity in male antigen potentiates the effect of low-grade inflammation on compromising fetal and pregnancy health.