Multiple injections of anti-mouse 尾2glycoprotein 1 antibody induce FcR纬-dependent fetal growth restriction (FGR) in mice

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• 作者：R. Kawaguchi^a ; ^{kawaguchi-rie@jikei.ac.jp} ; S. Nunomura^b ; N. Umehara^a ; T. Nikaido^c ; B. Huppertz^d ; T. Tanaka^a ; C. Ra^b
• 关键词：Antiphospholipid antibody syndrome (APS) ; Fetal growth restriction (FGR) ; Mouse model ; Anti-尾2 glycoprotein I (a尾2GPI) antibody ; FcR纬 deficient mice
• 刊名：Placenta
• 出版年：2012
• 期刊代码：260_01434004
• 类别：med
• 出版时间：July, 2012
• 卷：33
• 期：7
• 页码：540-547
• 文件大小：1632 K

摘要

Objectives

The antiphospholipid syndrome (APS) is characterized by the presence of circulating antiphospholipid antibodies (aPLs), is a leading cause for thromboembolic events, repeated miscarriage, fetal loss and is a major risk factor for fetal growth restriction (FGR) and preeclampsia. In human, anti-尾2 glycoprotein I (a尾2GPI) antibody is one of the aPLs and considered to be a specific and important marker for APS. However, pathophysiological changes induced by a尾2GPI antibodies in FGR are largely unknown.

Methods

In the present study, we developed a murine FGR model induced by multiple injections of WBCAL-1, a well-characterized mouse a尾2GPI monoclonal antibody.

Results

Administration of WBCAL-1, but not the isotype control antibody and saline, into pregnant mice specifically decreased the size of fetuses and placentas without affecting the number of delivered pups. Also, a significant increase in urinary albumin and electron microscopic changes, such as splitting layers of basal membranes in the placental labyrinth and rearrangement of pores in glomerular endothelial cells, were observed in WBCAL-1 treated mice. WBCAL-1 injection did not induce any changes in blood pressure and typical parameters of blood thromboembolic symptoms. Furthermore, FcR纬 deficiency protected the fetuses from a尾2GPI antibody-induced injuries.

Conclusions

Our present findings suggest that proteinuria is a symptom associated with APS-related FGR with placental and renal tissue injuries, and that FcR纬 might be a molecular target for prevention of a尾2GPI antibody-mediated obstetrical pathologies.