Prebreeding Maternal Immunostimulation with Freund's Complete Adjuvant Reduces Placental Damage and Distal Limb Defects Caused by Methylnitrosourea

Authors

  • Mary Renee Prater,

    1. Department of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Blacksburg, VA;
    2. Department Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, VA Tech, Blacksburg, VA, USA
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  • Kurt L. Zimmerman,

    1. Department Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, VA Tech, Blacksburg, VA, USA
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  • Chelsea L. Laudermilch,

    1. Department Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, VA Tech, Blacksburg, VA, USA
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  • Steven D. Holladay

    1. Department Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, VA Tech, Blacksburg, VA, USA
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M. Renee Prater, Assistant Professor, The Edward Via Virginia College of Osteopathic Medicine, Department of Biomedical Sciences, 2265 Kraft Drive, Blacksburg, VA 24060, USA.
E-mail: mrprater@vt.edu

Abstract

Problem  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.

Method of study  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.

Results  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.

Conclusion  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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