Pregnancy-Induced Metabolic
Phenotype Variations in Maternal Plasma
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Abstract
Metabolic
variations occur during normal pregnancy to provide the growing fetus
with a supply of nutrients required for its development and to ensure
the health of the woman during gestation. Mass spectrometry-based
metabolomics was employed to study the metabolic phenotype variations
in the maternal plasma that are induced by pregnancy in each of its
three trimesters. Nontargeted metabolomics analysis showed that pregnancy
significantly altered the profile of metabolites in maternal plasma.
The levels of six metabolites were found to change significantly throughout
pregnancy, with related metabolic pathway variations observed in biopterin
metabolism, phospholipid metabolism, amino acid derivatives, and fatty
acid oxidation. In particular, there was a pronounced elevation of
dihydrobiopterin (BH<sub>2</sub>), a compound produced in the synthesis
of dopa, dopamine, norepinephrine, and epinephrine, in the second
trimester, whereas it was markedly decreased in the third trimester.
The turnover of BH<sub>2</sub> and tryptophan catabolites indicated
that the fluctuations of neurotransmitters throughout pregnancy might
reveal the metabolic adaption in the maternal body for the growth
of the fetus. Furthermore, 11 lipid classes and 41 carnitine species
were also determined and this showed variations in the presence of
long-chain acylcarnitines and lysophospholipids in later pregnancy,
suggesting changes of acylcarnitines and lysophospholipids to meet
the energy demands in pregnant women. To our knowledge, this work
is the first report of dynamic metabolic signatures and proposed related
metabolic pathways in the maternal plasma for normal pregnancies and
provided the basis for time-dependent metabolic trajectory against
which disease-related disorders may be contrasted