Screening, Identification and Preliminary Investigation of Target Transporters in Pregnancy Pathologies

Huang, Xiao; Ontsouka, Edgar; Lüthi, Michael; Hediger, Matthias; Jain, Arjun; Baumann, Marc Ulrich; Surbek, Daniel; Anderle, Pascale; Albrecht, Christiane (March 2014). Screening, Identification and Preliminary Investigation of Target Transporters in Pregnancy Pathologies. Reproductive sciences, 21(3), 183A-183A. Sage

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Screening, Identification and Preliminary Investigation of Target
Transporters in Pregnancy Pathologies.
INTRODUCTION: Pre-eclampsia (PE), intrauterine growth restriction
(IUGR) and gestational diabetes mellitus (GDM) are major sources of
clinical morbidity and mortality in pregnant women worldwide. The
mechanisms underlying these gestational diseases are complex and not
yet fully understood, but one factor contributing to their development is
impaired maternal-fetal nutrient transport. Therefore, we aimed to identify
candidate membrane transporters involved in transplacental nutrient
transfer associated with PE/IUGR or GDM.
METHODS: Using in silico strategies, we analysed various gene
expression data sets generated on different platforms focusing on
solute carriers, ABC transporters and TRP channels in order to identify
transporters that are differently expressed between patients and gestational
age-matched controls. These bioinformatic analyses were combined with
literature data to define a catalogue of target transporters that could be
involved in the development of PE/IUGR or GDM. Transporters of interest
were then analysed for gene expression using qRT-PCR in placental
tissues of patients and controls. For validating the results on protein and
functional level, we started to establish an in vitro assay using freshly
isolated primary cytotrophoblast cells polarized on the Transwell® system.
RESULTS: Using bioinformatics approaches, we initially identified
37 target membrane proteins which were mainly associated with the
transport of amino acids, vitamins, and trace elements. At the current state
of analysis, the amino acid transporters SLC7A7, SLC38A2, SLC38A5,
and the thiamine transporter SLC19A3 showed significant differences in
placental mRNA expression between controls and patients affected by
PE and/or IUGR. Subsequent gene expression analysis in our in-house
GDM placental tissue bank is still ongoing.
CONCLUSIONS: Based on our in silico analyses, literature data and
first follow-up in vitro validations, we were able to define potentially
interesting candidate transporters implicated in PE/IUGR or GDM. To
date, additional newly defined candidate targets are being analysed on
mRNA level in PE/IUGR and GDM. Subsequent analyses on protein and
functional level will reveal whether these targets could be of diagnostic
or therapeutical interest in these pregnancy pathologies.

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