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Loss of maternal annexin A5 increases the likelihood of placental platelet thrombosis and foetal loss.

ABSTRACT: Antiphospholipid syndrome is associated with an increased risk of thrombosis and pregnancy loss. Annexin A5 (Anxa5) is a candidate autoantigen. It is not known, however, whether endogenous Anxa5 prevents foetal loss during normal pregnancy. We found significant reductions in litter size and foetal weight in Anxa5-null mice (Anxa5-KO). These changes occurred even when only the mother was Anxa5-KO. A small amount of placental fibrin deposition was observed in the decidual tissues, but did not noticeably differ between wild-type and Anxa5-KO mice. However, immunoreactivity for integrin beta 3/CD61, a platelet marker, was demonstrated within thrombi in the arterial canals only in Anxa5-KO mothers. Subcutaneous administration of the anticoagulant heparin to pregnant Anxa5-KO mice significantly reduced pregnancy loss, suggesting that maternal Anxa5 is crucial for maintaining intact placental circulation. Hence, the presence of maternal Anxa5 minimises the risk of thrombosis in the placental circulation and reduces the risk of foetal loss.

SUBMITTER: Ueki H

PROVIDER: S-EPMC3494014 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Loss of maternal annexin A5 increases the likelihood of placental platelet thrombosis and foetal loss.

Ueki Hiroshi H Mizushina Tomona T Laoharatchatathanin Titaree T Terashima Ryota R Nishimura Yasuhiro Y Rieanrakwong Duangjai D Yonezawa Tomohiro T Kurusu Shiro S Hasegawa Yoshihisa Y Brachvogel Bent B Pöschl Ernst E Kawaminami Mitsumori M

Scientific reports 20121109

Antiphospholipid syndrome is associated with an increased risk of thrombosis and pregnancy loss. Annexin A5 (Anxa5) is a candidate autoantigen. It is not known, however, whether endogenous Anxa5 prevents foetal loss during normal pregnancy. We found significant reductions in litter size and foetal weight in Anxa5-null mice (Anxa5-KO). These changes occurred even when only the mother was Anxa5-KO. A small amount of placental fibrin deposition was observed in the decidual tissues, but did not noti ...[more]

PMID: 23145320

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Project description:Annexin A5 (ANXA5), which is known as a protein with anticoagulative function, may play a role in triglyceride biosynthesis. Triglycerides are involved in lipid and energy metabolism, which are important in the elucidation of obesity. To investigate the association between single-nucleotide polymorphisms (SNPs) of ANXA5 and obesity in a Korean population, 372 participants (213 overweight/obese individuals and 159 control subjects) were enrolled from the Kyung Hee University Medical Center and Keimyung University Dongsan Medical Center. The genotypes of five SNPs (rs12510548, rs4240260, rs3756281, rs13136094 and rs6534313) were evaluated in ANXA5 using the multiple logistic regression analysis with the codominant 1, codominant 2, dominant, recessive and log-additive models. The genotype and allele frequencies of the five investigated SNPs exhibited significant differences between the control and the overweight/obese groups: rs12510548 (P=0.004 in the codominant 2 model, P=0.0019 in the recessive model, P=0.027 in the log-additive model and P=0.026 in allele frequencies); rs4240260 (P=0.002 and Fisher's exact P=0.0006 in the codominant 2 model, P=0.0007 and Fisher's exact P=0.0007 in the recessive model, P=0.020 and Fisher's exact P=0.0019 in the log-additive model and P=0.020 in allele frequencies); rs3756281 (P=0.016 in the codominant 2 model and P=0.0094 in the recessive model); rs13136094 (P=0.0030 and Fisher's exact P=0.0011 in the codominant 2 model, P=0.0012 and Fisher's exact P=0.0013 in the recessive model, P=0.034 and Fisher's exact P=0.0035 in the log-additive model and P=0.024 in allele frequencies); and rs6534313 (P=0.0010 and Fisher's exact P=0.0003 in the codominant 2 model, P=0.0003 and Fisher's exact P=0.0003 in the recessive model, P=0.0075 and Fisher's exact P=0.0010 in the log-additive model and P=0.005 in allele frequencies). Two haplotypes were weakly associated with obesity (GGATG, P=0.037 and CAGCC, P=0.020). Results of the present study suggested that ANXA5 may be associated with the development of obesity in a Korean population.

Dataset Information

Loss of maternal annexin A5 increases the likelihood of placental platelet thrombosis and foetal loss.

Publications

Loss of maternal annexin A5 increases the likelihood of placental platelet thrombosis and foetal loss.

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