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Mol. Hum. Reprod. Advance Access originally published online on August 31, 2007
Molecular Human Reproduction 2007 13(11):807-814; doi:10.1093/molehr/gam061
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Administration of high-dose intact immunoglobulin has an anti-resorption effect in a mouse model of reproductive failure

Masamitsu Takeda1,2, Hideto Yamada2, Kazuya Iwabuchi1, Shigeki Shimada2,3, Makoto Naito4, Noriaki Sakuragi2, Hisanori Minakami2 and Kazunori Onoé1,5

1Division of Immunobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, Hokkaido, Japan 2Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan 3 The Scripps Research Institute, La Jolla, CA, USA 4Division of Cellular and Molecular Pathology, Department of Cellular Function, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

5 Correspondence address. Tel: +81-11-706-5532; Fax: +81-11-706-7545; E-mail: kazunori{at}igm.hokudai.ac.jp

Administration of high-dose intact human immunoglobulin (IH-Ig) has been applied to treat a variety of inflammatory and autoimmune diseases, and is expected to have beneficial effects on human fecundity. In the present study, we investigated whether Ig had anti-resorption effects using polyinosinic-polycytidylic acid sodium salt [poly (I:C)]-induced enhancement of fetal resorption in the mating of CBA/J x DBA/2J resorption-prone mouse model. Furthermore, we investigated the mechanism of the effect by examining the mRNA expression of interferon (IFN)-{gamma}, tumor necrosis factor (TNF)-{alpha}, IL-10, IL-4 and TGF-ß1 in spleens and placentas from the resorption-prone model treated with IH-Ig, by reverse transcription (RT)–polymerase chain reaction (PCR). Administration of high-dose IH-Ig significantly reduced the fetal resorption rate from 55% to 10%. This anti-resorption effect, however, was not detected in mice administered with Fab fragments of human Ig. We then performed adoptive transfer experiments to examine whether cellular components could transfer the effect. A remarkable anti-resorption effect was seen in poly (I:C)-injected pregnant recipients transferred with spleen cells from IH-Ig-treated donor mice. The RT–PCR study showed that IH-Ig reduced the expression of IFN-{gamma} and TNF-{alpha} mRNA in placentas of poly (I:C)-injected pregnant mice. The present findings demonstrate that intact Ig, particularly its Fc portion, possesses anti-resorption activity. The effect might be attributed to the suppressed production of pro-inflammatory cytokines at the maternofetal interface.

Key words: immunoglobulin/fetal resorption/spleen/mouse model

Submitted on July 3, 2007; resubmitted on August 14, 2007; accepted on August 21, 2007.


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