The embryotoxicity of sera from patients with autoimmune diseases on post-implantation rat embryos in culture persists during remission and is not related to oxidative stress

Author:

Ergaz Z.1,Mevorach D.2,Goldzweig G.3,Cohen A.2,Patlas N.4,Yaffe P.4,Blank M.5,Shoenfeld Y.5,Ornoy A.4

Affiliation:

1. Laboratory of Teratology, Israel Canada Institute of Medical Research, Hebrew University Hadassah Medical School, Jerusalem, Israel, Department of Neonatology, Hadassah-Hebrew University Hospital, Mount Scopus, Jerusalem, Israel,

2. Laboratory for Cellular and Molecular Immunology, Department of Medicine, Hebrew University Hadassah Medical School, Jerusalem, Israel

3. The Clinical Psychology Division, School of Behavioral Sciences, The Academic College Tel-Aviv-Yaffo, Israel

4. Laboratory of Teratology, Israel Canada Institute of Medical Research, Hebrew University Hadassah Medical School, Jerusalem, Israel

5. The Autoimmune Disease Center, Department of Medicine, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Israel

Abstract

We evaluated the embryolethality and embryotoxicity of sera from patients suffering from autoimmune diseases during remission on post-implantation rat embryos cultured on these sera and determined the association between the patients’ clinical history, high blood levels of specific antibodies, medications, and oxidative stress parameters. One hundred and eighty, 10.5-day-old rat embryos were cultured in their yolk sacs in 33 sera of systemic lupus erythematosus (SLE)/antiphospholipid syndrome (APS) patients, and compared with 84 embryos cultured in rat sera and 88 embryos cultured in control human sera. The sera proved to be lethal and embryotoxic but not teratogenic resulting in smaller yolk sacs and embryos, lower protein level and lower developmental score. Significantly less embryos cultured in ‘toxic’ SLE/APS sera had peak 2 of low molecular weight antioxidants (LMWA) wave, implying a delayed maturation of the antioxidant defense. Lower peak 1 of LMWA correlated with a history of recurrent abortions. Embryonic levels of superoxide dismutase (SOD) and catalase (CAT) did not correlate with sera toxicity, patients’ clinical history or specific antibodies. We conclude that SLE/APS patients’ clinical remission did not prevent death or developmental delay accompanied by later appearance of peak 2 of LMWA in post-implantation rat embryo cultures. The normal levels of the antioxidant enzymes evaluated may indicate that sera toxicity is not related to oxidative stress. Lupus (2010) 19, 1623—1631.

Publisher

SAGE Publications

Subject

Rheumatology

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