The decidua of preeclamptic-like BPH/5 mice exhibits an exaggerated inflammatory response during early pregnancy. (April 2017)

• Record Type: Journal Article
• Authors: Heyward, C.Y.; Sones, J.L.; Lob, H.E.; Yuen, L.C.; Abbott, K.E.; Huang, W.; Begun, Z.R.; Butler, S.D.; August, A.; Leifer, C.A.; Davisson, R.L.
• Is Part Of: Journal of reproductive immunology. Volume 120(2017)
• Page Start: 27
• Page End: 33
• Publication Date: 2017-04
• Subjects: Macrophages -- T cells -- iNOS -- IL-10 -- Tolerance; CSF-1 Colony stimulating factor -- Cox-2 Cyclooxygenase-2 -- DAPI 4′, 6-diamidino-2-phenylindole -- dMØ Decidual macrophages -- e embryonic day -- iNos inducible nitric oxide synthase -- NK Natural Killer cells -- NKr1 regulatory natural killer cells -- PGE2 Prostaglandin E2 -- UPP Reduced Uterine Perfusion Pressure -- Tr1 type 1 regulatory T cells -- VEGF vascular endothelial growth factor; Reproduction -- Immunological aspects -- Periodicals; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Reproduction -- Periodicals; Reproduction -- Immunologie -- Périodiques; Immunologie -- Périodiques; Immunology; Reproduction -- Immunological aspects; Periodicals; Electronic journals; Electronic journals; 615.766
• DOI: 10.1016/j.jri.2017.04.002
• Languages: English
• ISSNs: 0165-0378

Abstract

Highlights: The BPH/5 preeclamptic-like mouse exhibits an overall reduction in decidual macrophages. Loss of decidual macrophages is concurrent with a decrease in the immunosuppressive cytokine IL-10 and increased iNOS. Loss of immune suppression in BPH/5 decidua is associated with increases in activated T cells. Abstract: Preeclampsia is a devastating complication of pregnancy characterized by late-gestation hypertension and proteinuria. Because the only definitive treatment is delivery of the fetus and placenta, preeclampsia contributes to increased morbidity and mortality of both mother and fetus. The BPH/5 mouse model, which spontaneously develops a syndrome strikingly similar to preeclampsia, displays excessive inflammation and suppression of inflammation improves pregnancy outcomes. During early pregnancy, decidual macrophages play an important role in promoting maternal tolerance to fetal antigens and regulating tissue remodeling, two functions that are critical for normal placental development. BPH/5 pregnancies are characterized by abnormal placentation; therefore, we hypothesized that macrophage localization and/or function is altered during early pregnancy at the site of placental formation (the decidua) compared to C57BL/6 controls. At early gestation time points, before the onset of maternal hypertension or proteinuria, there was a reduction in the number of macrophages in BPH/5 decidua and a concomitant increase in activated T cells compared with C57BL/6. BPH/5 decidua also exhibited decreased expression of the immunosuppressive cytokine, IL-10, and increased expression of pro-inflammatory, inducible nitric oxide synthase. Together, these data suggest that a reduction in decidual macrophages during pregnancy is associated with immune activation in BPH/5 mice, inadequate placental development and may contribute to adverse pregnancy outcomes in this model.