【关键词】  retinoids

    the Institute of Laboratory Medicine, Department of Clinical Chemistry, Lund University, Lund, Sweden.

    ABSTRACT

    Background: Retinoids are vital for embryonic development; both excesses and deficiencies of vitamin A are known to give similar patterns of birth defects. Concentrations of retinol in newborns and in pregnant women have been investigated, but concentrations of the biologically active metabolite all-trans retinoic acid and its isomer 13-cis retinoic acid have not.

    Objective: We measured serum concentrations of these retinoid derivatives in newborns and their mothers and in women in the first trimester of pregnancy, when embryonic differentiation (organogenesis) takes place.

    Design: In this descriptive study, 10 newborns from normal deliveries and their mothers and 16 healthy women in their first trimester of pregnancy were studied. Seventeen healthy women served as control subjects. all-trans and 13-cis Retinoic acid and retinol concentrations were measured by HPLC.

    Results: The newborns had significantly lower retinol concentrations (1.0 μmol/L) than did their mothers (1.7 μmol/L; P = 0.013). Serum all-trans retinoic acid was also significantly lower in the newborns (3.4 nmol/L) than in their mothers (5.8 nmol/L; P = 0.008). In addition, serum concentrations of 13-cis retinoic acid were significantly lower in the newborns (2.0 nmol/L) than in their mothers (2.6 nmol/L; P = 0.005). The serum concentrations of all-trans retinoic acid and retinol did not correlate in any group.

    Conclusion: Retinol concentrations do not accurately reflect the concentrations of the biologically active derivative all-trans retinoic acid.

    Key Words: 13-cis Retinoic acid  all-trans retinoic acid  retinoids  vitamin A  newborns  pregnancy  mothers  maternal-fetal exchange  teratogens

    INTRODUCTION

    Vitamin A is a group of substances that have vitamin A activity. The most important of these substances are retinol (the precursor of the metabolically active derivatives) and the active metabolites all-trans retinoic acid, 9-cis retinoic acid, and retinal. The most abundant retinoids in serum are retinol and all-trans, 4-oxo-13-cis and 13-cis (inactive metabolite) retinoic acids. Retinoids are vital for vision, the immune system, reproduction, the differentiation and proliferation of cells, and embryonic development. The mechanism involved in embryonic development probably involves the retinoid nuclear receptors, which bind all-trans retinoic acid, 9-cis retinoic acid, or both retinoic acids. This interaction activates or represses the transcription of retinoic acid responsive genes.

    Both excess and deficiency of vitamin A are known to give similar patterns of birth defects (14). Evidence suggests that 13-cis retinoic acid is involved in teratogenicity (5), probably by isomerization to all-trans retinoic acid (6). Different species are sensitive in different ways to such teratogenic effects (7), possibly as a result of differences in