Reduced Placental Taurine Transporter (TauT) Activity in Pregnancies Complicated by Pre-eclampsia and Maternal Obesity - Advances in Experimental Medicine and Biology - page 86

from fetus to placenta in PE. STB basal membrane expresses TauT (Roos et al. 2004 )
and vesicle studies show that the activity of TauT in this membrane is not affected by
FGR (Norberg et al. 1998 ). In situ, TauT on the BM would transport taurine from the
fetus into STB but the influence of BM TauT activity on net maternal-fetal taurine
flux has not been determined in normal or compromised pregnancy. Studies of mater-
nal, placental, and fetal taurine levels in PE and maternal obesity following caesarian
section delivery, as well as taurine uptake and efflux mechanisms on STB MVM and
BM, are required to gain a better understanding of the relationships beween taurine
concentration, TauT activity, and delivery of taurine to the fetus.
In renal epithelial cells, TauT activity is down-regulated by PKC-induced phos-
phorylation of the transporter (Han et al. 2006 ) and activation of PKC in JAr cells
inhibits TauT activity (Kulanthaivel et al. 1991 ). STB expresses several PKC iso-
forms (Tertrin-Clary et al. 1990 ; Ruzycky et al. 1996 ), and these can be activated in
cytotrophoblast cells in vitro by NPY, a hyopthalamic peptide that is also produced
by STB, through activation of Y1 and Y3 receptors on the MVM (Robidoux et al.
1998 ). As NPY levels in maternal serum are higher in PE than normal pregnancy
(Khatun et al. 2000 ), and elevated in obese compared to ideal-weight individuals in
the general population (Baltazi et al. 2011 ), we investigated whether NPY could
downregulate TauT activity in STB. NPY treatment of villous tissue (2 h) induced a
small but significant reduction in TauT activity at pathophysiologically relevant
concentrations (Petraglia et al. 1989 ). We also confirmed previous reports that the
PKC activator PMA reduces STB TauT activity (Roos et al. 2004 ). It is possible that
NPY is a modulator of TauT activity that is common to both PE and obesity and
future work will address whether PCK is activated in PE and obesity and whether
there is an increase in phosphorylated TauT compared to normal pregnancy.

9.5 Conclusion

STB TauT activity is lower in placentas of obese mothers compared to mothers of ideal
weight and inversely related to maternal BMI in both the first trimester and at term.
STB TauT activity is also lower in PE compared to normal pregnancy. We propose that
this reduction in TauT activity lowers STB taurine concentration which impairs STB
renewal and reduces taurine transfer to the fetus, contributing to the increased risk of
FGR in these conditions. The fall in STB TauT activity with increasing maternal BMI
in the first trimester could predispose to abnormal STB renewal and development of PE
later in pregnancy. The PKC activator, NPY, caused a small but significant reduction in
TauT activity and could downregulate TauT in both PE and obesity. Determining the
reasons for, and consequences of, reduced placental TauT activity could lead to strate-
gies to improve pregnancy outcome and fetal growth in obesity and PE.

Acknowledgements The authors thank the midwives and nursing staff of St. Mary's Hospital for
their assistance in obtaining placentas. The research was funded by The Wellcome Trust, Action
Medical Research, and Tommy's (Let's Talk Baby).