Differential roles of inflammation and apoptosis in initiation of mid-gestational abortion in malaria-infected C57BL/6 and A/J mice. Issue 7 (July 2015)

• Record Type: Journal Article
• Authors: Sarr, D.; Bracken, T.C.; Owino, S.O.; Cooper, C.A.; Smith, G.M.; Nagy, T.; Moore, J.M.
• Is Part Of: Placenta. Volume 36:Issue 7(2015:Jul.)
• Page Start: 738
• Page End: 749
• Publication Date: 2015-07
• Subjects: Placental malaria -- Apoptosis -- Inflammation -- Pregnancy -- Abortion -- Plasmodium chabaudi AS; PM placental malaria -- iRBC infected red blood cell -- ED experiment day -- IP infected pregnant -- TUNEL terminal uridine deoxynucleotidyl transferase dUTP nick-end labeling -- UP uninfected pregnant -- cPARP cleaved poly (ADP-ribose) polymerase -- CASP3 total caspase 3 -- cCASP3 cleaved caspase 3 -- IP-A infected pregnant aborting -- IP-NA infected pregnant non-aborting; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2015.04.007
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Introduction: Plasmodium chabaudi AS-infection in pregnant A/J and C57BL/6J mice results in mid-gestational pregnancy loss. Although associated with increased systemic and placental pro-inflammatory responses and coagulopathy, the molecular mechanisms that underlie poor pregnancy outcomes in these mice are not yet fully understood. This study investigates the relationships between inflammation, apoptosis and malaria-induced pregnancy loss. Methods: Infection with P. chabaudi AS in early murine pregnancy and term human placental tissues from an endemic setting were assessed by histology, immunohistochemistry, TUNEL staining, real-time PCR, flow cytometry, western blot, and ELISA. Results: Quantitative PCR reveals accumulation of lymphocytes and monocytes and upregulation of chemokines that attract these cell types in malaria-exposed mid-gestational A/J conceptuses. Monocyte accumulation is confirmed by flow cytometry and placental immunohistochemistry. Concurrent with initiation of malaria-induced abortion, markers of apoptosis are evident in the junctional zone, but not the labyrinth, of A/J placentae. In contrast, mid-gestation conceptuses in infected C57BL/6J lack evidence for monocyte accumulation, exhibiting low or no in situ placental staining despite trophoblast immunoreactivity for the monokine, CCL2. Additionally, placental apoptosis is not consistently observed, and when evident, appears after malaria-induced abortion typically initiates. Similarly, trophoblast apoptosis in term human placental malaria is not observed. Of those studied, a sole common feature of malaria-induced abortion in A/J and C57BL/6J mice is elevation of plasma tumor necrosis factor. Discussion: Consistent with our previous observations, tumor necrosis factor is likely to be a central driver of malaria-induced pregnancy loss in both strains, but likely operates through mechanisms distinct from placental apoptosis in C57BL/6J mice. Highlights: Early Plasmodium chabaudi AS-infection in pregnant mice is associated with mid-gestational pregnancy loss. Transcripts of leucocytes are upregulated in conceptuses and monocytes accumulate. Mid-gestational trophoblast apoptosis is only observed in the Junctional zone but not the labyrinth. Apoptosis is only observed in infiltrating leucocytes in term human placental malaria.