Interferon-induced class II expression at the spongiotrophoblastic zone of the murine placenta is linked to fetal rejection and developmental abnormalities.
Type II interferon is known to induce a plethora of gene expression involved in the humoral and cellular immunity. One of the multiple sites of action of gamma-IFN is the fetoplacental unit, where its role has not yet been clearly defined. We have previously shown in vitro that gamma-IFN may induce expression of class II MHC antigens on the spongiotrophoblast layer of the murine placenta, which under physiological conditions is negative for these antigens. Indeed, the absence of class II antigens from the placenta could be part of a mechanism evoked by fetal tissues to escape a host vs. graft reaction. In the present study we show that intraperitoneal in vivo administration of low doses of recombinant gamma-IFN to pregnant females specifically induces class II antigens on the spongiotrophoblast zone, increases fetal abortion, causes retardation of eye development in the fetuses and decreases fetal weight. This treatment also affects the maternal pathology as we witness a prominent hypersplenism in the mother accompanied by low levels of haematocrit, elevated IgG production and decreased granulocytic and thrombocytic counts. These results are specifically linked to the pregnant state of the mother, since virgin females do not develop any of the above abnormalities. Our results not only point to a new dimension in gamma-IFN's role during pregnancy, but may be of clinical importance for prophylaxis since administration of gamma-IFN to a pregnant female may lead to abortion, fetal abnormalities or cause haematologic disorders to the mother.
Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.
S
S
Vassiliadis
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D
Tsoukatos
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I
Athanassakis
D000014:Abnormalities, Drug-Induced; D000034:Abortion, Veterinary / Q000139:chemically induced*; D000740:Anemia / Q000139:chemically induced; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001772:Blood Cell Count / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D010920:Placenta / Q000276:immunology*; D011247:Pregnancy; D013163:Splenomegaly / Q000139:chemically induced; D014327:Trophoblasts / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007371:Interferon-gamma