Placental transporter activity and expression in relation to fetal growth

Sibley, Colin P.; Glazier, Jocelyn D.; D'Souza, S W

doi:10.1113/expphysiol.1997.sp004034

Cited by 79 publications

(62 citation statements)

References 41 publications

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“…It is well established that maternal stress (changes in nutrition or glucocorticoid administration) during pregnancy can restrict fetal growth and induce adult disease. Changes in gross morphology and ultrastructure of the placenta are interrelated and lead to alterations in surface area, vascularity, barrier thickness, and cell composition of the placenta, all of which influence placental transport characteristics (Sibley et al 1997). It is therefore likely that altered placental morphology, growth and/or function underpin the changes in fetal growth and increased disease risk in models of prenatal undernutrition, and/or prenatal glucocorticoid exposure.…”

Section: Discussionmentioning

confidence: 99%

Maternal betamethasone administration reduces binucleate cell number and placental lactogen in sheep

Braun

Li²,

Moss³

et al. 2007

Journal of Endocrinology

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The placenta may mediate glucocorticoid-induced fetal growth restriction. Previous studies have examined effects of fetal cortisol in sheep, which reduces placental binucleate cell (BNC) number; the source of ovine placental lactogen (oPL). The effects of maternal GC are unknown. Therefore, this study examined the effects of maternal betamethasone (BET) administration on BNC number, distribution, placental oPL protein levels, and maternal and fetal plasma oPL levels. Pregnant ewes were randomized to receive injections of saline or one (104 days of gestation; dG), two (104 and 111 dG), or three (104, 111, and 118 dG) doses of BET (0 . 5 mg/kg). Placental tissue was collected before, during, and after the period of BET treatment. Fetal (121-146 dG) and placental (121 dG) weights were decreased after BET when compared with controls. In controls, the mean number of BNCs increased until 132 dG and decreased thereafter. Placental oPL protein levels peaked at 109 dG and remained stable thereafter. Maternal plasma oPL levels in controls increased across gestation; fetal plasma oPL levels decreased. BNCs were reduced by 24% to 47% after BET when compared with controls at all ages studied. Placental oPL protein levels, maternal, and fetal plasma oPL levels were also reduced after BET injections, but recovered to values that were not different to controls near term. BET disrupted the normal distribution of BNCs within the placentome. These data may suggest a placental role in growth restrictive effects of prenatal maternal BET exposure through alterations in placental output of oPL, a key metabolic hormone of pregnancy.

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Section: Discussionmentioning

confidence: 99%

Maternal betamethasone administration reduces binucleate cell number and placental lactogen in sheep

Braun

Li²,

Moss³

et al. 2007

Journal of Endocrinology

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“…The nutrient transfer capacity of the placenta, which is dependent on adequate placental development and growth, plays a critical role in fetal growth trajectory allowing for fetal growth to reach its potential in both humans and animals [49,50]. In humans and other mammals, fetal growth is dependent on the placental supply of oxygen and nutrients which are provided through two main processes, simple diffusion and transporter-mediated transfer, respectively [51]. The major fetal nutrients are glucose (and its metabolic byproduct, lactate) and amino acids [52,53].…”

Section: Placental Transport Of Oxygen and Nutrientsmentioning

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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“…For example, they cannot tell whether the increase is as a result of changed localisation of transporters or of increased transcription or translation. Our data are particularly important given the central role of system A in amino acid transport in the placenta (Sibley et al 1997, Cramer et al 2002 and the fact that it is exquisitely sensitive to changes in fetal growth (or that changes in expression cause changes in fetal growth). The TEER and […”

Section: Discussionmentioning

confidence: 99%

Expression and adaptive regulation of amino acid transport system A in a placental cell line under amino acid restriction

Jones¹,

Ashworth²,

Page³

et al. 2006

Reproduction

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Trans-placental transport of amino acids is vital for the developing fetus. Using the BeWo cell line as a placental model, we investigated the effect of restricting amino acid availability on amino acid transport system type A. BeWo cells were cultured either in amino acid-depleted (without non-essential amino acids) or control media for 1, 3, 5 or 6 h. System A function was analysed using a(methyl-amino)isobutyric acid (MeAIB) transcellular transport studies. Transporter (sodium coupled neutral amino acid transporter (SNAT1/2)) expression was analysed at mRNA and protein level by Northern and Western blotting respectively. Localisation was carried out using immunocytochemistry. MeAIB transcellular transport was significantly (P < 0.05) increased by incubation of the cells in amino acid-depleted medium for 1 h, and longer incubation times caused further increases in the rate of transfer. However, the initial response was not accompanied by an increase in SNAT2 mRNA; this occurred only after 3 h and further increased for the rest of the 6-h incubation. Similarly, it took several hours for a significant increase in SNAT2 protein expression. In contrast, relocalisation of existing SNAT2 transporters occurred within 30 min of amino acid restriction and continued throughout the 6-h incubation. When the cells were incubated in medium with even lower amino acid levels (without non-essential plus 0.5 3 essential amino acids), SNAT2 mRNA levels showed further significant (P < 0.0001) up-regulation. However, incubation of cells in depleted medium for 6 h caused a significant (P 5 0.014) decrease in the expression of SNAT1 mRNA. System L type amino acid transporter 2 (LAT2) expression was not changed by amino acid restriction, indicating that the responses seen in the system A transporters were not a general cell response. These data have shown that placental cells adapt in vitro to nutritional stress and have identified the physiological, biochemical and genomic mechanisms involved. Reproduction (2006) 131 951-960

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Placental transporter activity and expression in relation to fetal growth

Cited by 79 publications

References 41 publications

Maternal betamethasone administration reduces binucleate cell number and placental lactogen in sheep

Maternal betamethasone administration reduces binucleate cell number and placental lactogen in sheep

The pregnant sheep as a model for human pregnancy

Expression and adaptive regulation of amino acid transport system A in a placental cell line under amino acid restriction

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