Vitamin A Deficiency During Rat Pregnancy Alters Placental TNF-α Signalling and Apoptosis

Authors

  • CHRISTOS ANTIPATIS,

    1. CHRISTOS ANTIPATIS
      CHERYL J. ASHWORTH
      LISA HANNAH
      NIGEL HOGGARD
      RICHARD G. LEA
      The Rowett Research Institute, Bucksburn, Aberdeen, Scotland, UK,
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  • CHERYL J. ASHWORTH,

    1. CHRISTOS ANTIPATIS
      CHERYL J. ASHWORTH
      LISA HANNAH
      NIGEL HOGGARD
      RICHARD G. LEA
      The Rowett Research Institute, Bucksburn, Aberdeen, Scotland, UK,
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  • SIMON C. RILEY,

    1. SIMON C. RILEY
      Department of Obstetrics and Gynaecology, Centre for Reproductive Biology, University of Edinburgh, Edinburgh, UK
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  • LISA HANNAH,

    1. CHRISTOS ANTIPATIS
      CHERYL J. ASHWORTH
      LISA HANNAH
      NIGEL HOGGARD
      RICHARD G. LEA
      The Rowett Research Institute, Bucksburn, Aberdeen, Scotland, UK,
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  • NIGEL HOGGARD,

    1. CHRISTOS ANTIPATIS
      CHERYL J. ASHWORTH
      LISA HANNAH
      NIGEL HOGGARD
      RICHARD G. LEA
      The Rowett Research Institute, Bucksburn, Aberdeen, Scotland, UK,
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  • RICHARD G. LEA

    1. CHRISTOS ANTIPATIS
      CHERYL J. ASHWORTH
      LISA HANNAH
      NIGEL HOGGARD
      RICHARD G. LEA
      The Rowett Research Institute, Bucksburn, Aberdeen, Scotland, UK,
    Search for more papers by this author

Address reprint requests to Richard G. Lea, Ovine Pregnancy Group, Division of Integrative and Developmental Biology, Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB, Scotland, UK. E-mail: R.Lea@rri.sari.ac.uk

Abstract

PROBLEM: Vitamin A is important for immune function and deficiency is associated with adverse pregnancy outcome. In the rat, vitamin A deficiency reduces both foetal number and neonatal survival. The role of the placenta is uncertain. The effects of maternal vitamin A deficiency on placental cytokines and apoptosis have been investigated.

METHOD OF STUDY: Pregnant rats were fed either control or vitamin A free (VAF) diets (n=4/group) from 8 weeks prior to and throughout pregnancy. Day 20 placentas from viable foetuses were examined for immunoexpression of (a) cytokines: tumour necrosis factor-α (TNF-α), TNFR1 receptor (p55), leptin and leptin receptor, (b) apoptosis: TdT-mediated dUTP nick end-labelling (TUNEL) positive cells, bax and bcl-2.

RESULTS: Placentas from VAF rats, but not controls, exhibited an infiltrate of neutrophils positive for TNF-α and leptin. The number of TNFR1 (p55) and TUNEL positive trophoblast cells was increased specifically in areas of neutrophil infiltration. Trophoblast giant cells in VAF placentas exhibited reduced bax but no change in bcl-2.

CONCLUSIONS: Maternal vitamin A deficiency is associated with abnormal placental apoptosis induced by neutrophil derived TNF-α acting through the TNFR1 (p55) and/or a change in the bcl-2/bax ratio in the trophoblast giant cells. These changes may underlie the effects of vitamin A deficiency on foetal development.

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