Nonspecific stimulation of the maternal immune system. I. Effects on teratogen-induced fetal malformations

Background: Maternal immune stimulation has reported, but unconfirmed, effi cacy for reducing chemical-induced morphologic defects in mice. Methods: Teratogenic chemicals (2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD], ethyl carbamate [urethane], methylnitrosourea [MNU], or valproic acid [VA] ) were given to pregnant mice to induce cleft palate (TCDD, urethane), digi tal defects (urethane, MNU), or exencephaly (VA). Before teratogen administ ration, the immune system of female mice was stimulated by intraperitoneal (IP) administration of pyran copolymer or attenuated bacillus Calmette Guer in (BCG), or by footpad injection with Freund's complete adjuvant (FCA). Results: Fetal defects caused by all four chemicals studied were reduced by maternal immunostimulation, sometimes dramatically. In addition to reducin g VA-induced exencephaly, immunostimulation with FCA resulted in fetal mice displaying anury (absence of tails). Activated maternal immune cells could not be detected in fetal circulation using flow cytometry and a fluorescen t cell-tracking probe. Conclusions: For the chemicals tested, maternal immune stimulation has effi cacy in reducing fetal defects. Immune protection against teratogenesis may be an indirect effect of maternal immune cell activation. (C) 2000 Wiley-L iss, Inc.