These regions are hypo-methylated upon differentiation in vitro

The system L transporter, a sodium independent transporter, is involved in the transport of branched chain essential amino acids, e.g leucine and phenylalanine. The mTOR and JAK/STAT signalling pathways play a central role in the regulation of placental amino acid transporter activity and are modulated in pregnancy complications associated with altered fetal growth. Decreased placental system A activity accompanied by changes in the mTOR signalling cascade have been illustrated in pregnancies complicated by IUGR, and increased activities in diabetic pregnancies contribute to altered fetal growth patterns. One of the few studies available examining the effect of anticoagulants on amino acid transport reported a decrease in the transport of the amino acid histidine has been reported after ASA treatment of rat intestine. We tested the hypothesis that placental system A and L activity are affected by hypoxic oxygen conditions and that LMWHs or ASA interact with placental villi in a non-anticoagulant Lumefantrine manner to affect placental amino acid transport. Our work supports the hypothesis that hypoxia induces placental Linolenic acid dysfunction and affects placental nutrient transport. In this study we employed an ex vivo placental villous fragment model to explore the hypothesis that hypoxic conditions exert negative effects on placental amino acid transporter activities and that the anticoagulants dalteparin and acetylsalicylic acid are capable of neutralizing negative effects of low oxygen conditions on placental amino acid transport. Our data demonstrate that in a hypoxic environment the activities of the system A and L amino acid transporters are opposingly affected. We observed a significant decrease in villous explant system A activity and an increase in system L activity in response to low levels of oxygen compared to standard culture conditions. An intermediate oxygen level of 8% O2 also enhanced transport of amino acids by system L compared to standard culture conditions. Under hypoxic conditions dalteparin and ASA did not exert a beneficial or rescuing effect on transporter activities. However, under standard culture conditions therapeutic levels of dalteparin interacted with third trimester placental villi in a manner that is predicted to have negative effects upon the placental system A and L transport.

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