Abstract

Immunostimulation reduces murine teratogen-induced birth defects. It is unclear if placental improvement contributes to this outcome. The current study examined murine placental ultrastructure and fetal limb development following maternal methylnitrosourea (MNU) exposure, +/-Freund's complete adjuvant (FCA) immunostimulation. Two murine strains (CD-1, C57BL/6N) were administered MNU on gestation day 9 (GD9), FCA pre-breeding, or FCA + MNU. Fetal limb and placental development were examined on GD14. MNU decreased placental weight and reduced placental cellular viability; FCA reversed these effects. MNU shortened fetal limbs and increased digital defects in both strains. Placentas were less damaged in C57BL/6N versus CD-1 mice, and distal limb malformations improved only in CD-1 mice. FCA immunostimulation also increased pregnancy rate. Improved fetal outcome from immune-stimulated mice may not be dependent on improved placental morphology. However, placental function and morphology in immune-stimulated mice may not directly correlate, thus functional improvements should be examined for possible relationship to reduced birth defects.

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