Placental improvement and reduced distal limb defects by maternal interferon-gamma injection in methylnitrosourea-exposed mice.

Background: Methylnitrosourea (MNU), an alkylating agent derived from creatinine metabolism, is cytotoxic, genotoxic, and mutagenic. Mid-gestational exposure to MNU leads to distal limb defects in mice. Previous studies have shown that nonspecific maternal immune stimulation protects against MNU-induced teratogenesis.

Reduced birth defects caused by maternal immune stimulation in methylnitrosourea-exposed mice: association with placental improvement.

Background: Methylnitrosourea (MNU) is a potent carcinogen and teratogen that is associated with central nervous system, craniofacial, skeletal, ocular, and appendicular birth defects following transplacental exposure at critical time points during development, and preliminary studies have suggested that nonspecific maternal immunostimulation may offer protection against development of these birth defects.

Methods: Our study examined morphologic alterations in fetal limb and digital development and placental integrity following maternal exposure to MNU on GD 9 in CD-1 mice, and characterized the improvement in placental integrity and abrogation of fetal defects following maternal immune stimulation with interferon-gamma (IFN-gamma) on GD 7.

Results: Fetal limbs were significantly shortened (p < 0.