Biology Reference
In-Depth Information
Pre-eclampsia (PE) is a serious condition affecting 5% of pregnancies worldwide
and is the leading cause of maternal and fetal mortality (Hibbard and Milner
1994
;
CESDI
1998
). Those fetuses that survive are at increased risk of FGR and associated
morbidities. The aetiology of the disease is complex but its origin lies in abnormal
placental development and function (Roberts and Gammill
2005
) and the only treat-
ment for PE is premature delivery of the placenta and baby. The incidence of PE rises
with increasing maternal body mass index (BMI) and is four times higher in mor-
bidly obese women compared to their ideal weight counterparts (Mbah et al.
2010
) .
The reason that maternal obesity is a major risk factor for developing PE is not
understood but as obesity, and in particular morbid obesity, is increasing in women
of reproductive age (Heslehurst et al.
2010
; Mbah et al.
2010
) the incidence of PE is
likely to rise in parallel. Maternal obesity is itself associated with abnormal fetal
growth, increasing the risk of stillbirth with FGR fivefold compared to mothers of
ideal weight (Nohr et al.
2005
) .
As normal fetal growth and development depend on the appropriate supply of
taurine by the placenta we hypothesised that, in common with idiopathic FGR, a
reduction in STB TauT activity in maternal obesity and PE could contribute to the
increased risk of FGR evident in these conditions. We determined STB TauT activ-
ity in placental villous tissue isolated from first trimester and term pregnancies and
related activity to maternal BMI at booking. In separate studies we compared STB
TauT activity in PE with normal pregnancy. As TauT activity in renal cells is inhib-
ited by protein kinase C (PKC)-induced phosphorylation (Han et al.
2006
) , we
explored the possibility that TauT activity is modulated by neuropeptide Y (NPY),
a hypothalamic peptide that activates PKC in STB (Robidoux et al.
1998
) , is ele-
vated in obese individuals (Baltazi et al.
2011
), and is higher in maternal plasma in
PE compared to normal pregnancy (Khatun et al.
2000
) .
9.2
Methods
9.2.1
Tissue Acquisition and Ethical Approval
Placentas were obtained with written informed consent as approved by the Central
Manchester Research Ethics Committee. First trimester placentas (7-13 weeks ges-
tation) were obtained following elective medical or surgical termination of preg-
nancy. Gestational age was estimated from the date of last menstrual period and
confirmed by ultrasound dating. Term placentas (38-40 weeks gestation) were col-
lected following caesarean section or vaginal delivery from uncomplicated single-
ton pregnancies. Maternal BMI was determined either at admission (studies of first
trimester placentas) or at booking (~12 weeks: studies of term placentas) and women
defined as ideal weight (BMI 18.5-24.9), overweight (25-29.9), or obese (>30).
Placentas were also collected from women (BMI <30) with PE (defined as hyper-
tension >140/90 mmHg in previously normotensive women plus proteinuria
>300 mg/L in a 24-h urine collection after 20 weeks gestation).
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