title: Differential roles of inflammation and apoptosis in initiation of mid-gestational abortion in malaria-infected C57BL/6 and A/J mice.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Tropical and Emerging Global Diseases and Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA. Electronic address: dsarr1@uga.edu.
authors.forename: D
authors.initials: D
authors.lastname: Sarr
authors.affiliation: Center for Tropical and Emerging Global Diseases and Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Bracken
authors.affiliation: Center for Tropical and Emerging Global Diseases and Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
authors.forename: S O
authors.initials: SO
authors.lastname: Owino
authors.affiliation: Center for Tropical and Emerging Global Diseases and Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Cooper
authors.affiliation: Center for Tropical and Emerging Global Diseases and Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Smith
authors.affiliation: Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
authors.forename: T
authors.initials: T
authors.lastname: Nagy
authors.affiliation: Center for Tropical and Emerging Global Diseases and Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Moore
mesh_terms: D000022:Abortion, Spontaneous / Q000469:parasitology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D018932:Chemokine CCL2 / Q000097:blood; D018925:Chemokines / Q000032:analysis; D005260:Female; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D007962:Leukocytes / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D008288:Malaria / Q000150:complications*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000473:pathology; D010920:Placenta / Q000737:chemistry / Q000469:parasitology / Q000473:pathology; D016788:Plasmodium chabaudi; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000473:pathology / Q000503:physiopathology*; D014327:Trophoblasts / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000097:blood
chemical_list: D018932:Chemokine CCL2; D018925:Chemokines; D014409:Tumor Necrosis Factor-alpha
keywords: Abortion; Apoptosis; Inflammation; Placental malaria; Plasmodium chabaudi AS; Pregnancy