Reduced Placental Taurine Transporter (TauT) Activity in Pregnancies Complicated by Pre-eclampsia and Maternal Obesity - Advances in Experimental Medicine and Biology - page 85

cytotrophoblast cells followed by differentiation, fusion, and incorporation of
their nuclei into the STB (Huppertz et al. 2006 ; Heazell and Crocker 2008 ) . STB
volume is maintained by the deportation of aged nuclei into maternal blood.
Coordination of STB renewal is critical for normal pregnancy and cellular turn-
over is dysregulated in PE (Crocker et al. 2003 ; Heazell and Crocker 2008 ) and
maternal obesity (Higgins et al. 2011 ). This dysregulation causes the release of
toxic material from STB into maternal blood which can initiate a widespread
inflammatory response in the mother and trigger PE (Roberts and Gammill 2005 ) .
Using cytotrophoblast cells in vitro, we showed that knocking down TauT expres-
sion with siRNA inhibited TauT activity, reduced intracellular taurine, and inhib-
ited the differentiation and fusion of cells to form multinucleate syncytia (Parsons
et al. 2009 ). In addition, TauT knockdown increased apoptosis in response to
TNFa (Desforges et al. 2010 ), a cytokine that is elevated in PE (Tosun et al.
2010 ) and maternal obesity (Challier et al. 2008 ). Thus, the reduction in TauT
activity and intracellular taurine in PE could impair STB renewal and lower cyto-
protection to damaging cytokines, leading to reduced nutrient delivery to the
fetus and the release of necrotic material to the mother. The fall in STB TauT
activity with increasing maternal BMI, particularly in the first trimester, could
predispose to abnormal STB renewal later in pregnancy and might in part explain
the increased incidence of PE in obese mothers.
The reduction in STB TauT activity in FGR is not associated with a change in
expression (Roos et al. 2004 ) and our preliminary data show that TauT protein
expression is also unaffected by PE (Hirst et al. 2012 ) or morbid obesity (unpub-
lished observation). This suggests that the low STB TauT activity in these conditions
of pregnancy is due to post-translational down-regulation of transporter activity.
Regulation of TauT activity has not been studied extensively in placenta but in com-
mon with other tissues, activity in trophoblast-derived choriocarcinoma cells (JAr)
shows adaptive regulation in response to altered taurine concentration (Jayanthi et al.
1995 ). As maternal plasma taurine concentration is higher in the first trimester of
pregnancies that subsequently develop FGR, compared to those that proceed nor-
mally (Di Giulio et al. 2004 ), adaptive down-regulation could contribute to the
reduced STB TauT activity in FGR. However, the reduction in STB TauT activity in
FGR has been demonstrated at 32-39 weeks (Norberg et al. 1998 ) and at this later
stage of gestation maternal plasma taurine concentration is reported to be unchanged
(Economides et al. 1989 ) or significantly lower (Cetin et al. 1990 ) in FGR than nor-
mal pregnancy. In PE without FGR, maternal plasma taurine does not differ from
normal (Evans et al. 2003 ) and, although it has yet to be measured in obese mothers
in late pregnancy, plasma taurine levels are lower in obese individuals in the general
population compared to their ideal weight counterparts (Zhang et al. 2004 ) . Therefore
it is unlikely that the reduced STB TauT activity in PE and obesity is caused by adap-
tive down-regulation. It is of interest that, following labour, the taurine concentration
in umbilical blood of normally grown fetuses is reported to be higher in PE than
normal pregnancy (Evans et al. 2003 ). Bearing in mind that STB TauT activity was
shown to be reduced in PE in the current study, it is possible that higher umbilical
plasma taurine arises from altered fetal metabolism and/or reduced uptake of taurine