Biology Reference
In-Depth Information
Chapter 9
Reduced Placental Taurine Transporter (TauT)
Activity in Pregnancies Complicated
by Pre-eclampsia and Maternal Obesity
Michelle Desforges , Andrea Ditch fi eld , Chloe R. Hirst , Claire Pegorie ,
Kathryn Martyn-Smith , Colin P. Sibley , and Susan L. Greenwood
Abstract
Taurine is an important nutrient in intrauterine life, being required for
fetal organ development and cellular renewal of syncytiotrophoblast (STB), the
nutrient transport epithelium of the placenta. As taurine is conditionally essential in
human pregnancy, the fetal and placental demand for taurine is met by uptake from
maternal blood into STB through the activity of TauT. Pre-eclampsia (PE) and
maternal obesity are serious complications of pregnancy, associated with fetal
growth restriction (FGR) and abnormal renewal of STB, and maternal obesity is a
major risk factor for PE. Here we test the hypothesis that STB TauT activity is
reduced in maternal obesity and PE compared to normal pregnancy.
STB TauT activity, measured in fragments of placental tissue, was negatively
related to maternal BMI over the range 18-46 kg/m
2
in both the first trimester (7-12
weeks gestation) and at term (
p
< 0.01; linear regression). Neither TauT activity nor
expression in the first trimester differed to normal pregnancy at term. STB TauT
activity was significantly lower in PE than normal pregnancy (
p
< 0.01). Neuropeptide
Y (NPY), a protein kinase C (PKC) activator which is elevated in PE and obesity,
reduced STB TauT activity by 20% (50 pM-50 nM: 2 h) (
p
< 0.03). Activation of
PKC by phorbol 12-myristate-13-acetate (1 mM) reduced TauT activity by 18%
(
p
< 0.05). As TauT activity is inhibited by phosphorylation, we propose that NPY
activates PKC in the STB which phosphorylates TauT in PE and maternal obesity.
Reduced TauT activity could contribute to dysregulated renewal of STB and
FGR that are common to PE and maternal obesity.
M. Desforges A. Ditch fi eld C. R. Hirst C. Pegorie
K. Martyn-Smith C. P. Sibley S. L. Greenwood (
*
)
Maternal and Fetal Health Research Centre, Institute of Human Development,
Manchester Academic Health Sciences Centre, University of Manchester,
Manchester M13 9WL , UK
e-mail: susan.greenwood@manchester.ac.uk
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