Amino Acid and Lipid

Placenta Nutrient Transport

Rina Gustuti
Changes in placenta nutrients transport  directly contribute to the
development of abnormal fetal growth  detail information on the
mechanism by which placental nutrients transporter are regulated 
help us to better understand how pregnancy complication develop 
for designing novel intervention strategies
Factors influence transport across the placenta :
 Uteroplacental and umbilical blood flows
 Placental metabolism
 Activity/expression of specific transporter proteins in the placental
barier
 Factors Regulating Placental Nutrient Transporters

The syncytiotrophoblast represent the primary barrier

for transfer of nutrients from mother to the fetus
Placental function is regulated by  factors
of fetal , maternal and placental origin
Fetal fc fetal signals affecting
placental function ; Fetal IGF II level
are reduced in IUGR fetuses , and
higher in LGA fetuses  ex; Fetal
PTHrp level regulates activity of the
calcium pump in the BM
Maternal fc adipokines, hormones,
nutrients  have been investigated in
various models
Placental fac placental signaling pathway
Schematic of major transfer mechanism across the MVM (Micro vilous
Membran) and BM (Basal Membran)
 Amino Acid across the placenta
 Amino acid uptake across cellular membranes   Fetal amino acid concentration are generally
accumulative transporter and exchangers higher than maternal levels  active transport
 Accumulative transporters mediating up take mechanism across the placenta
against their concentration gradients usually by
cotransporting extracellular sodium
 Exchanger  exchanging amino acids between
the intracellular and extracellular compartements
 The human placenta express more than 20
different amino acid transporters

Amino acid transpoters :

1. System A
Regulation of placental System A activity?
2. System L
Regulation of placental System L activity?
3. Taurine
Regulation of placental Taurine transport?
 System A amino acid transporter
Facilitate uptake of small non essential neutral
amino acids such as alanin, glycine and serine
System A activity is thus important for placental
transport of both non essential and essential
amino acids.
Human first and third placenta express three
isoform of system A : SNAT1, SNAT2 and SNAT4
System A activity  increased with advancing
gestation
IUGR Placenta system A transporter activity
is reduced
Regulation of placental system A activity 
cytokines and hormones
Insulin, IL-6, TNF stimulate activity of System
A transposter
Placental signaling pathway regulating
system A activity  m TOR is a
integrator of maternal, fetal and
placental signaling molecules (hormones,
growth factor and nutrient levels)
 IUGR mTOR signaling reduced
 Dexametason stimulates system A
activity increased SNAT2 expression
 Leptin stimulate system A
 Insulun stimulate system A in third
trimester preganancy
 Reduced system A  hypoxia, IL 1ß,
CRH
 System L amino acid transporter
 The system L transporter is a sodium
independent obligatory exchanger of neutral
amino acids.
Non-essential amino acids are exchanged for
predominantly essential amino acids (leucine and
phenylalanine)
The system L transporter consists of LAT1 ,
LAT2, LAT3, LAT4, 4F2hc/CD98 (SLC3A2), TAT1
LAT1 cellular localization >> MVM
LAT2  cellular localization >>BM
 System L higher activity in the MVM  if
decrease  reduced fetal growth
 Regulation of placental system L activity IL6,
TNFalfa,adiponectin ???
 Insulin  increased system L activity
 M TOR signaling  positive regulator
of system L
 mTOR inhibitor  prevented increase
in leucine uptake
 Activation of protein kinase C 
increased intracellular calcium level 
increase expression of 4F2hc and
LAT1 stimulate system L
 Cocain, nicotine use during
pregnancy reduced fetal maternal
transport of amino acid by system L,
system A  fetal lower birth weight
 Taurine
 Taurine is regarded as essential for the fetus
because the ability to synthesize this amino acid
is low or absent during fetal life.
The taurine transporter (system β, TauT;
SLC6A6) mediates cellular taurine uptake against
its concentration gradient energized by
cotransport with sodium and chloride
The taurine transporter is more active in the
MVM compared to the BM
 Activity of the taurine transporter has been
reported as reduced in MVM, but not BM,
isolated from IUGR placentas
Regulation of Placental Taurine
Transport Uptake of taurine in villous
tissue from human placenta is not
affected by cytokines or hormones, such
as IGF-I and II, IL-1β, IL-6, GH, leptin, TNF-
α , inhibiting mTOR
mTOR positive regulator of taurine
transport in cultured trophoblast cells
High glucose levels decrease taurine
uptake in cultured trophoblast cells.
 Lipid and Fatty Acids across the placenta
• During uncomplicated gestation, the maternal
lipid profile shifts from an anabolic to a catabolic
state results gestational hyperlipidemia
• The human fetus at delivery has ’12–15% fat, the
remainder being fat-free (lean body) mass.
• Research overgrowth and undergrowth
associated with GDM and FGR are the result of
changes in fat mass and not in lean body mass.
• This indicates that alterations in fetal fat are key
processes underlying the fetal phenotype in
GDM and FGR.
• Whereas fetal fat-free mass is mostly regulated
by genetic factors, fetal fat accretion appears to
be determined by the intrauterine environment
Mechanisms involved in the uptake of circulating
maternal fatty acids by placental tissue
Placental tissue takes up maternal circulating free fatty
acids (FFAs) that cross the placenta passive diffusion
Placental lipoprotein lipase is an enzyme thought to
hydrolyze maternal plasma triglycerides into FFA for
placental uptake and transfer
Endothelial lipase in human placenta at term high
phospholipase activity, which implies that not only
triglycerides but also phospholipids may provide fatty
acids for placental transfer to the fetus
human placental tissue expresses receptors to very-
low-density lipoprotein, LDL, and HDL which could
provide fatty acids to the placenta for fetal transfer once
they are released by phospholipase A2 and intracellular
lipase
Different proteins that transport fatty acids have been
identified: fatty acid translocase, fatty acid transport
protein (FATP) which is composed of 6 different proteins
(FATP-1, -2, -3, -4, -5 and -6), and the plasma membrane
fatty acid-binding protein (FABPpm)
 Lipid and Fatty Acids across the placenta
long-chain polyunsaturated fatty acids (LC-PUFAs), particularly
arachidonic acid and docosahexaenoic acid (DHA, 22:6n–3), are
deposited in fetal tissues during pregnancy this process is
facilitated by placental delivery.
Studies have shown a significantly higher ratio of 13C-DHA in cord to
maternal plasma compared with other fatty acids higher placental
DHA transfer.
The materno-fetal transfer of fatty acids is a slow process that
requires 12 h.
DHA in cord blood lipids correlates with placental messenger RNA
expression of fatty acid transport protein (FATP)-4
Impaired materno-fetal LC-PUFA transport has been proposed in
pregnancies complicated by abnormal placental function (eg, due to
gestational diabetes mellitus or intrauterine growth restriction)
Given that placental DHA transfer is important for child outcomes,
elucidation of its potential modulation by transport mechanisms,
maternal diet, and disease appears to be important.
 Lipid and Fatty Acids across the placenta
• Human brain structure is composed of lipids (’50–60% of dry matter) and includes
high proportions of long-chain polyunsaturated fatty acids (LC-PUFAs), especially
docosahexaenoic acid (DHA)and arachidonic acid
• DHA and AA are highly concentrated in cell membranes of the retina and brain, and
they are important modulators of membrane function, neurogenesis, photoreceptor
differentiation, activation of the visual pigment rhodopsin, protection against
oxidative stress, the activity of several enzymes, the function of ion channels, and
the concentrations and metabolism of neurotransmitters and eicosanoids
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