Developmental retardation in neonates of aldehyde reductase (AKR1A)-deficient mice is associated with low ascorbic acid and high corticosterone levels

J Nutr Biochem. 2021 May;91:108604. doi: 10.1016/j.jnutbio.2021.108604. Epub 2021 Feb 4.

Abstract

Aldehyde reductase encoded by the Akr1a gene catalyzes the NADPH-dependent reduction of a variety of aldehyde compounds, and it plays a role in the biosynthesis of ascorbic acid (AsA) by converting D-glucuronate to L-gulonate. Although supplementing drinking water with AsA (1.5 mg/mL) ameliorates the fertility of Akr1a-/- (KO) female mice, litter sizes in the KO mice are typically smaller than those for Akr1a+/+ (WT) mice, and about one-third of the neonates have a reduced stature. Half of the neonates in the smallest, developmentally retarded group died before weaning, and the remaining half (less than 6 g in weight) also barely grew to adulthood. While no difference was found in the number of fetuses between the KO and WT mice at 14.5-embryonic days, the sizes of the KO fetuses had already diverged. Among the organs of these retarded KO neonates at 30 d, the spleen and thymus were characteristically small. While an examination of spleen cells showed the normal proportion of immune cells, apoptotic cell death was increased in the thymus, which would lead to thymic atrophy in the retarded KO neonates. Plasma AsA levels were lower in the small neonates despite the fact that their mothers had received sufficient AsA supplementation, and the corticosterone levels were inversely higher compared to wild-type mice. Thus, insufficient AsA contents together with a defect in corticosterone metabolism might be the cause of the retarded growth of the AKR1A-deficient mice embryos and neonates.

Keywords: Akr1a; Ascorbic acid; Corticosterone; Growth retardation; Knockout mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Reductase / genetics*
  • Animals
  • Animals, Newborn
  • Ascorbic Acid / blood*
  • Blood Cell Count
  • Corticosterone / blood*
  • Female
  • Fetal Growth Retardation / blood
  • Fetal Growth Retardation / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pregnancy

Substances

  • Akr1a1 protein, mouse
  • Aldehyde Reductase
  • Ascorbic Acid
  • Corticosterone