PMID- 25819809
OWN - NLM
STAT- MEDLINE
DCOM- 20160225
LR  - 20161125
IS  - 1532-3102 (Electronic)
IS  - 0143-4004 (Linking)
VI  - 36
IP  - 6
DP  - 2015 Jun
TI  - Involvement of hypoxia and inflammation in early pregnancy loss mediated by Shiga 
      toxin type 2.
PG  - 674-80
LID - S0143-4004(15)00862-0 [pii]
LID - 10.1016/j.placenta.2015.03.005 [doi]
AB  - INTRODUCTION: Symptomatic or asymptomatic Shiga toxin producing Escherichia coli 
      (STEC) infections during early pregnancy may cause maternal or fetal damage 
      mediated by Shiga toxin type 2 (Stx2). The aim of this study is to elucidate the 
      mechanisms responsible for early pregnancy loss in rats treated with Stx2. 
      METHODS: Sprague Dawley pregnant rats were intraperitoneally injected at day 8 of 
      gestation with a sublethal dose (0.5 ng of Stx2/g of total body weight, 250 mul) 
      of purified Stx2. Control rats were injected with the same volume of PBS. The 
      expression of globotriaosylceramide (Gb3) glycosphingolipid receptor for Stx2 was 
      evaluated by thin-layer chromatography (TLC). Regions of hypoxia in decidual 
      tissue were determined by pimonidazole immunohistochemistry and vascular 
      endothelial growth factor (VEGF) expression by Western blot and 
      immunohistochemistry. Tumor necrosis factor-alpha (TNF-alpha) levels in serum and 
      decidual tissue were evaluated by ELISA. Serum progesterone levels were 
      determined by RIA. RESULTS: Decidual tissue from both, control and Stx2-treated 
      rats showed similar expression of Gb3 receptor. Intrauterine growth restriction 
      was observed in Stx2-treated rats, associated with hypoxia and an increase of 
      decidual TNF-alpha levels. Decrease of serum progesterone levels and decidual VEGF 
      expression were also demonstrated. DISCUSSION: Our findings indicate that Stx2 
      reaches the uteroplacental unit, binds Gb3 and triggers damage in decidual 
      tissue. Poor oxygen supply accompanied with damage in the uteroplacental unit and 
      inflammation could be responsible for the early pregnancy loss. Decrease in the 
      pregnancy protective factors, serum progesterone and local VEGF, may contribute 
      to the pregnancy loss.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Sacerdoti, F
AU  - Sacerdoti F
AD  - Laboratorio de Fisiopatogenia, Departamento de Fisiologia, Instituto de 
      Fisiologia y Biofisica Bernardo Houssay (IFIBIO Houssay-CONICET), Facultad de 
      Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
FAU - Amaral, M M
AU  - Amaral MM
AD  - Laboratorio de Fisiopatogenia, Departamento de Fisiologia, Instituto de 
      Fisiologia y Biofisica Bernardo Houssay (IFIBIO Houssay-CONICET), Facultad de 
      Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
FAU - Aisemberg, J
AU  - Aisemberg J
AD  - CEFYBO-CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.
FAU - Cymeryng, C B
AU  - Cymeryng CB
AD  - CEFYBO-CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.
FAU - Franchi, A M
AU  - Franchi AM
AD  - CEFYBO-CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.
FAU - Ibarra, C
AU  - Ibarra C
AD  - Laboratorio de Fisiopatogenia, Departamento de Fisiologia, Instituto de 
      Fisiologia y Biofisica Bernardo Houssay (IFIBIO Houssay-CONICET), Facultad de 
      Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. Electronic 
      address: ibarra@fmed.uba.ar.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150314
PL  - Netherlands
TA  - Placenta
JT  - Placenta
JID - 8006349
RN  - 0 (Shiga Toxin 2)
RN  - 0 (Trihexosylceramides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 71965-57-6 (globotriaosylceramide)
SB  - IM
MH  - Abortion, Spontaneous/chemically induced/metabolism/*pathology
MH  - Animals
MH  - Female
MH  - Hypoxia/metabolism/*pathology
MH  - Inflammation/metabolism/*pathology
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Shiga Toxin 2
MH  - Trihexosylceramides/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Vascular Endothelial Growth Factor A/metabolism
OTO - NOTNLM
OT  - Hypoxia
OT  - Inflammation
OT  - Pregnancy loss
OT  - STEC
OT  - Stx2
EDAT- 2015/03/31 06:00
MHDA- 2016/02/26 06:00
CRDT- 2015/03/31 06:00
PHST- 2015/01/26 00:00 [received]
PHST- 2015/03/04 00:00 [revised]
PHST- 2015/03/06 00:00 [accepted]
PHST- 2015/03/31 06:00 [entrez]
PHST- 2015/03/31 06:00 [pubmed]
PHST- 2016/02/26 06:00 [medline]
AID - S0143-4004(15)00862-0 [pii]
AID - 10.1016/j.placenta.2015.03.005 [doi]
PST - ppublish
SO  - Placenta. 2015 Jun;36(6):674-80. doi: 10.1016/j.placenta.2015.03.005. Epub 2015 
      Mar 14.