Elevated maternal plasma concentrations of homocysteine (Hcy) are associated with pregnancy complications and adverse neonatal outcomes. The postulate that we wish to advance here is that placental transport of Hcy, by competing with endogenous amino acids for transporter activity, may account for some of the damaging impacts of Hcy on placental metabolism and function as well as fetal development. In this article, we provide an overview of some recent studies characterising the transport mechanisms for Hcy across the microvillous plasma membrane (MVM) of the syncytiotrophoblast, the transporting epithelium of human placenta. Three Hcy transport systems have been identified, systems L, A and y(+)L. This was accomplished using a strategy of competitive inhibition to investigate the effects of Hcy on the uptake of well-characterised radiolabelled substrates for each transport system into isolated MVM vesicles. The reverse experiments were also performed, examining the effects of model substrates on [³⁵S]L-Hcy uptake. This article describes the evidence for systems L, A and y(+)L involvement in placental Hcy transport and discusses the physiological implications of these findings with respect to placental function and fetal development.
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http://dx.doi.org/10.1007/s10545-010-9141-3 | DOI Listing |
J Nutr
December 2024
Division of Reproductive Sciences, Department of Obstetrics & Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States; Section of Neonatology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, United States. Electronic address:
Background: Pregnancies complicated by maternal obesity are characterized by metabolic differences affecting placental nutrient transport and fetal development. Docosahexaenoic acid (DHA) is critical for fetal brain development and is primarily incorporated into phosphatidylcholine (PC). Recent evidence suggests that choline may enhance PC-DHA synthesis; however, data on the impact of maternal plasma choline on placental phospholipid DHA content in females with obesity are limited.
View Article and Find Full Text PDFClin Sci (Lond)
November 2023
Department of Obstetrics and Gynecology, University of Colorado, Anschutz Medical Campus, Aurora, CO, U.S.A.
The System L amino acid transporter, particularly the isoform Large Neutral Amino Acid Transporter Small Subunit 1 (LAT1) encoded by SLC7A5, is believed to mediate the transfer of essential amino acids in the human placenta. Placental System L amino acid transporter expression and activity is decreased in pregnancies complicated by IUGR and increased in fetal overgrowth. However, it remains unknown if changes in the expression of LAT1 are mechanistically linked to System L amino acid transport activity.
View Article and Find Full Text PDFClin Sci (Lond)
April 2023
Department of Obstetrics & Gynecology, Division of Reproductive Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, U.S.A.
Pregnant women with obesity are more likely to deliver infants who are large for gestational age (LGA). LGA is associated with increased perinatal morbidity and risk of developing metabolic disease later in life. However, the mechanisms underpinning fetal overgrowth remain to be fully established.
View Article and Find Full Text PDFSci Rep
July 2022
Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovskeho 1203, 500 05, Hradec Králové, Czech Republic.
The human placenta represents a unique non-neuronal site of monoamine transporter expression, with pathophysiological relevance during the prenatal period. Monoamines (serotonin, dopamine, norepinephrine) are crucial neuromodulators for proper placenta functions and fetal development, including cell proliferation, differentiation, and neuronal migration. Accumulating evidence suggests that even a transient disruption of monoamine balance during gestation may lead to permanent changes in the fetal brain structures and functions, projecting into adulthood.
View Article and Find Full Text PDFReprod Toxicol
September 2022
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address:
Maternal obesity is associated with an increased risk of adverse pregnancy outcomes including stillbirth, and their etiology is thought to be related to placental and fetal hypoxia. In this study, we sought to investigate the levels of lactate in maternal and umbilical cord blood, a well characterized biomarker for hypoxia, and expression of plasma membrane lactate transporter MCT1 and MCT4 in the placental syncytiotrophoblast (STB), which are responsible for lactate uptake and extrusion, respectively, from pregnant women with a diagnosis of obesity following a Cesarean delivery at term. With use of approaches including immunofluorescence staining, Western blot, RT-qPCR and ELISA, our results revealed that in controls the expression of MCT1 was equally observed between basal (fetal-facing, BM) and microvillous (maternal-facing, MVM) membrane of the STB, whereas MCT4 was predominantly expressed in the MVM but barely detected in the BM.
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