Intrauterine Growth Restriction Is Associated with a Reduced Activity of Placental Taurine Transporters

Norberg, Staffan; Powell, Theresa L.; Jansson, Thomas

doi:10.1203/00006450-199808000-00016

Cited by 185 publications

(98 citation statements)

References 36 publications

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“…This is consistent with data reported for singleton IUGR pregnancies (14). A more recent study suggests that reduced plasma taurine concentrations in singleton IUGR fetuses is due to the reduced activity of placental taurine transporters (34). However, the physiologic function of this amino acid remains elusive.…”

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confidence: 81%

Discordant Amino Acid Profiles in Monochorionic Twins with Twin-Twin Transfusion Syndrome

et al. 2000

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To test the hypothesis that discordant growth in monochorionic (MC) twins occurs at least in part due to disparity in placental amino acid transporter function, we measured plasma amino acid levels by HPLC in maternal and fetal blood samples collected at birth from gestational age matched twins with (n ϭ 12) and without (n ϭ 12) twin-twin transfusion syndrome (TTTS). In the donor twin, fetal plasma concentrations and feto-maternal ratios of five essential amino acids-valine (p Ͻ 0.001), leucine (p Ͻ 0.001), iso-leucine (p Ͻ 0.05), histidine (p Ͻ 0.001) and L-arginine (p Ͻ 0.001)-were lower than the recipient and non-TTTS twin pairs. Fetal concentrations of the nonessential amino acids taurine (p Ͻ 0.001), serine (p Ͻ 0.01), glycine (p Ͻ 0.001) and tyrosine (p Ͻ 0.05) were also markedly lower in the donor than the recipient and non-TTTS twin pairs. In contrast, the fetal alanine level in the donor twin was higher than the recipient (664 Ϯ 64 versus 396 Ϯ 23 M; p Ͻ 0.001) and the non-TTTS twin pairs (p Ͻ 0.01). No such differences between amino acid profiles in non-TTTS MC twin pairs were found. Maternal plasma amino acid levels between TTTS and non-TTTS groups were comparable. This study provides the first evidence that certain amino acids in the donor twin of chronic TTTS differ significantly from those of the co-twin while others were comparable between twin pairs. These data, therefore, argue against inter-twin transfusion as the sole cause of growth restriction of the donor twin and suggests instead that impaired placental transport of amino acids may be a likely mechanism. Abbreviations MC, monochorionic F/M, feto-maternal ratio IUGR, intrauterine growth restriction TTTS, twin, twin transfusion syndrome AGA, appropriate for gestational age DC, dichorionic Perinatal death and postnatal handicap are more common in monochorionic (MC) than dichorionic (DC) twins (1). The high perinatal mortality in MC twins has been attributed to the presence of vascular anastomoses in the placenta, which may lead to twin-twin transfusion syndrome (TTTS) (2).Twin-twin transfusion syndrome is a chronic condition that presents in the early mid trimester of pregnancy, with characteristic discordance in fetal growth and amniotic fluid volume (1). Severe polyhydramnios develops in the larger "recipient" twin's sac, while oligohydramnios ensues in the growth restricted "donor" twin's sac. As pregnancy progresses, both fetuses are at a substantial risk of perinatal mortality and morbidity. The donor twin is at risk of the well described complications of severe intrauterine growth retardation, while the recipient twin may develop hydrops, cardiac dilatation, myocardial hypertrophy, tricuspid regurgitation, right ventricular outflow obstruction, and renal failure (3).Despite recent advances in the diagnostic and therapeutic modalities in fetal medicine, the treatment of chronic TTTS remains far from satisfactory (4, 5). This is attributed to the poor understanding of the patho-physiology of this enigmatic condition. Recent vascular anast...

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confidence: 81%

Discordant Amino Acid Profiles in Monochorionic Twins with Twin-Twin Transfusion Syndrome

et al. 2000

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“…In vivo studies of human FGR observed a reduced transport of the essential amino acids, leucine and phenylalanine [123]. Additional in vitro studies using microvillous fractions of human FGR placentas have shown a reduced transport of leucine, lysine, and taurine [124,125].…”

Section: Placental Amino Acid Transfer and Metabolismmentioning

confidence: 99%

The pregnant sheep as a model for human pregnancy

2008

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Successful outcome of human pregnancy not only impacts the quality of infant life and well-being, but considerable evidence now suggests that what happens during fetal development may well impact health and well-being into adulthood. Consequently, a thorough understanding of the developmental events that occur between conception and delivery is needed. For obvious ethical reasons, many of the questions remaining about the progression of human pregnancy can not be answered directly, necessitating the use of appropriate animal models. A variety of animal models exist for the study of both normal and compromised pregnancies, including laboratory rodents, non-human primates and domestic ruminants. While all of these animal models have merit, most suffer from the inability to repetitively sample from both the maternal and fetal side of the placenta, limiting their usefulness in the study of placental or fetal physiology under non-stressed in vivo conditions. No animal model truly recapitulates human pregnancy, yet the pregnant sheep has been used extensively to investigate maternal-fetal interactions. This is due in part to the ability to surgically place and maintain catheters in both the maternal and fetal vasculature, allowing repeated sampling from non-anesthetized pregnancies. Considerable insight has been gained on placental oxygen and nutrient transfer and utilization from use of pregnant sheep. These findings were often confirmed in human pregnancies once appropriate technologies became available. The purpose of this review is to provide an overview of human and sheep pregnancy, with emphasis placed on placental development and function as an organ of nutrient transfer.

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“…Uptake of radio-label was terminated by addition of 2 ml ice-cold PBS after 30 s (MeAIB, MVM), 150 s (MeAIB, BM) (31), or 8 s (all three essential amino acids) (29,30). Subsequently, vesicles were rapidly separated from the substrate medium by filtration on mixed ester filters (0.45 m pore size; Millipore Corporation, Bedford, MA) and washed with 3 ϫ 2 ml PBS.…”

Section: Methodsmentioning

confidence: 99%

“…The activity of the system A transporter was assessed using a modification of the protocol of Mahendran et al (28). The uptake into plasma membrane vesicles of the three essential amino acids L-lysine, L-leucine, and taurine was studied as described (29,30) with minor modifications. Vesicles were preloaded by incubation in 300 mmol/l mannitol and 10 mmol/l HEPES-Tris, pH 7.4, overnight at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Alterations in the Activity of Placental Amino Acid Transporters in Pregnancies Complicated by Diabetes

et al. 2002

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Alterations in placental transport may contribute to accelerated fetal growth in pregnancies complicated by diabetes. We studied the activity of the syncytiotrophoblast amino acid transporter system A and the transport of the essential amino acids leucine, lysine, and taurine. Syncytiotrophoblast microvillous plasma membranes (MVMs) and basal plasma membranes (BMs) were isolated from placentas obtained from normal pregnancies and pregnancies complicated by gestational diabetes mellitus (GDM) and type 1 diabetes, with and without large-for-gestational-age (LGA) fetuses. Amino acid transport was assessed using radio-labeled substrates and rapid filtration techniques. System A activity in MVM was increased (65-80%, P < 0.05) in all groups with diabetes independent of fetal overgrowth. However, MVM system A activity was unaffected in placentas of normal pregnancies with LGA fetuses. MVM leucine transport was increased in the GDM/LGA group. In BMs, amino acid transport was unaffected by diabetes. In conclusion, diabetes in pregnancy is associated with an increased system A activity in MVM, and MVM leucine transport is increased in the GDM/LGA group. We suggest that these changes result in an increased uptake of neutral amino acids across MVM, which may be used in placental metabolism or be delivered to the fetus. The increased MVM leucine uptake in the GDM/LGA group may contribute to accelerated fetal growth in these patients.

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Intrauterine Growth Restriction Is Associated with a Reduced Activity of Placental Taurine Transporters

Cited by 185 publications

References 36 publications

Discordant Amino Acid Profiles in Monochorionic Twins with Twin-Twin Transfusion Syndrome

Discordant Amino Acid Profiles in Monochorionic Twins with Twin-Twin Transfusion Syndrome

The pregnant sheep as a model for human pregnancy

Alterations in the Activity of Placental Amino Acid Transporters in Pregnancies Complicated by Diabetes

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