Vitamin A deficiency during rat pregnancy alters placental TNF-alpha signalling and apoptosis.
OBJECTIVE
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.


METHODS
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-alpha (TNF-alpha), 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-alpha 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-alpha 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.
Antipatis
Christos
C
The Rowett Research Institute, Bucksburn, Aberdeen, Scotland, UK.
Ashworth
Cheryl J
CJ
Riley
Simon C
SC
Hannah
Lisa
L
Hoggard
Nigel
N
Lea
Richard G
RG
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis; D005260:Female; D007150:Immunohistochemistry; D020738:Leptin / Q000032:analysis; D009504:Neutrophils / Q000737:chemistry / Q000502:physiology*; D010920:Placenta / Q000473:pathology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D011956:Receptors, Cell Surface / Q000032:analysis; D054411:Receptors, Leptin; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology*; D014802:Vitamin A Deficiency / Q000378:metabolism* / Q000473:pathology; D051028:bcl-2-Associated X Protein
D015703:Antigens, CD; C494828:Bax protein, rat; D020738:Leptin; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein