Nonspecific stimulation of the maternal immune system. I. Effects On teratogen-induced fetal malformations.
BACKGROUND
Maternal immune stimulation has reported, but unconfirmed, efficacy 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), digital defects (urethane, MNU), or exencephaly (VA). Before teratogen administration, the immune system of female mice was stimulated by intraperitoneal (IP) administration of pyran copolymer or attenuated bacillus Calmette Guérin (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 reducing 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 fluorescent cell-tracking probe.


CONCLUSIONS
For the chemicals tested, maternal immune stimulation has efficacy in reducing fetal defects. Immune protection against teratogenesis may be an indirect effect of maternal immune cell activation.
Holladay
S D
SD
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061-0442, USA. holladay@vt.edu
Sharova
L
L
Smith
B J
BJ
Gogal
R M
RM
Ward
D L
DL
Blaylock
B L
BL
D000014:Abnormalities, Drug-Induced / Q000196:embryology / Q000209:etiology / Q000517:prevention & control*; D000015:Abnormalities, Multiple / Q000196:embryology / Q000209:etiology / Q000517:prevention & control*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D002972:Cleft Palate / Q000139:chemically induced / Q000517:prevention & control; D003433:Crosses, Genetic; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D005528:Foot; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D007267:Injections; D007274:Injections, Intraperitoneal; D017880:Limb Deformities, Congenital / Q000139:chemically induced / Q000517:prevention & control; D008431:Maternal-Fetal Exchange; D008770:Methylnitrosourea / Q000633:toxicity*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009436:Neural Tube Defects / Q000139:chemically induced / Q000517:prevention & control; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy / Q000276:immunology*; D011713:Pyran Copolymer / Q000008:administration & dosage / Q000627:therapeutic use*; D013723:Teratogens / Q000633:toxicity*; D014520:Urethane / Q000633:toxicity*; D014635:Valproic Acid / Q000633:toxicity*
D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D000072317:Polychlorinated Dibenzodioxins; D013723:Teratogens; D011713:Pyran Copolymer; D014520:Urethane; D014635:Valproic Acid; D008770:Methylnitrosourea; D005620:Freund's Adjuvant