Placental glucose transporter 3 (GLUT3) is up-regulated in human pregnancies complicated by late-onset intrauterine growth restriction

Janzen, Carla; Lei, Margarida Y. Y.; Cho, John; Sullivan, Peggy; Shin, Bo‐Chul; Devaskar, Sherin U.

doi:10.1016/j.placenta.2013.08.010

Cited by 78 publications

(75 citation statements)

References 48 publications

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“…However, in growth-restricted fetuses similar to what we see in our maternal and paternal obesity in vivo models, both GLUT1 and GLUT3 gene expressions are known to be upregulated in human placentas (33). This has been proposed to occur as an adaptive mechanism to increase nutrient transport in late gestation to try and increase fetal growth (33). In addition, increases in gene expression of the amino acid transporter Slc38a2 is associated with faster-growing fetuses (14).…”

Section: Alterations To Fetal Health From Combined Paternal and Matersupporting

confidence: 65%

“…Glucose is transferred from the maternal blood to the fetus via the placenta through glucose transporters (43). However, in growth-restricted fetuses similar to what we see in our maternal and paternal obesity in vivo models, both GLUT1 and GLUT3 gene expressions are known to be upregulated in human placentas (33). This has been proposed to occur as an adaptive mechanism to increase nutrient transport in late gestation to try and increase fetal growth (33).…”

Section: Alterations To Fetal Health From Combined Paternal and Matersupporting

confidence: 63%

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When two obese parents are worse than one! Impacts on embryo and fetal development

McPherson

Bell

Zander-Fox

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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McPherson NO, Bell VG, Zander-Fox DL, Fullston T, Wu LL, Robker RL, Lane M. When two obese parents are worse than one! Impacts on embryo and fetal development. Am J Physiol Endocrinol Metab 309: E568 -E581, 2015. First published July 21, 2015; doi:10.1152/ajpendo.00230.2015.-The prevalence of overweight and obesity in reproductive-age adults is increasing worldwide. While the effects of either paternal or maternal obesity on gamete health and subsequent fertility and pregnancy have been reported independently, the combination of having both parents overweight/ obese on fecundity and offspring health has received minimal attention. Using a 2 ϫ 2 study design in rodents we established the relative contributions of paternal and maternal obesity on fetal and embryo development and whether combined paternal and maternal obesity had an additive effect. Here, we show that parental obesity reduces fetal and placental weights without altering pregnancy establishment and is not dependent on an in utero exposure to a high-fat diet. Interestingly combined parental obesity seemed to accumulate both the negative influences of paternal and maternal obesity had alone on embryo and fetal health rather than an amplification, manifested as reduced embryo developmental competency, reduced blastocyst cell numbers, impaired mitochondrial function, and alterations to active and repressive embryonic chromatin marks, resulting in aberrant placental gene expression and reduced fetal liver mtDNA copy numbers. Further understanding both the maternal cytoplasmic and paternal genetic interactions during this early developmental time frame will be vital for understanding how developmental programming is regulated and for the proposition of interventions to mitigate their effects. blastocyst; oocyte; sperm; embryo; fertility; infertility; obesity THE PREVALENCE OF OVERWEIGHT and obesity in reproductive-age adults is increasing worldwide (62). For example, in America it is estimated that 70.9% of males and 61.9% of women are classified as overweight/obese (62). The comorbidities associated with obesity have been well defined; however, until recently the impact on pregnancy and fetal development has been less recognized. Although the effects of either paternal or maternal obesity on gamete health and subsequent fertility and pregnancy have been reported independently, the combination of having both parents overweight/obese on fecundity and offspring health has received minimal attention. This information is essential, as the percentage of couples of reproductive age with both partners overweight/ obese is increasing and is the predominant situation in many countries (62).To date, there have only been three studies that have assessed the combined effects of maternal and paternal obesity on pregnancy and fetal health, two in human-assisted reproductive technology (ART) cohorts and one using a rodent high-fat diet model (41,67,76). These studies found no effect of maternal and paternal obesity on pregnancy establishment (41, 67, 76); however, when ...

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Section: Alterations To Fetal Health From Combined Paternal and Matersupporting

confidence: 65%

Section: Alterations To Fetal Health From Combined Paternal and Matersupporting

confidence: 63%

When two obese parents are worse than one! Impacts on embryo and fetal development

McPherson

Bell

Zander-Fox

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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“…; Janzen et al. ). Placental 11 β ‐hydroxysteroid dehydrogenase 2 (11 β HSD2) expression and activity was significantly reduced in deliveries complicated by IUGR compared with term or appropriately grown preterm deliveries, suggesting that increased intraplacental glucocorticoids may contribute to reduced substrate delivery in the IUGR pregnancy (Shams et al.…”

Section: Introductionmentioning

confidence: 99%

“…Placental insulin-like growth factor 2 (IGF2) and IGF1 mRNA expression were also increased at 55 and 90 days of gestation in hyperthermia-induced IUGR pregnancies (de Vrijer et al 2006). In humans, placental glucose transporter 1 (GLUT1) mRNA expression and protein abundance was decreased in the presence of an IUGR fetus, suggesting placental glucose transport capacity is impaired in these pregnancies (Dubova et al 2013;Janzen et al 2013). Placental 11b-hydroxysteroid dehydrogenase 2 (11bHSD2) expression and activity was significantly reduced in deliveries complicated by IUGR compared with term or appropriately grown preterm deliveries, suggesting that increased intraplacental glucocorticoids may contribute to reduced substrate delivery in the IUGR pregnancy (Shams et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Early restriction of placental growth results in placental structural and gene expression changes in late gestation independent of fetal hypoxemia

et al. 2016

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Placental restriction and insufficiency are associated with altered patterns of placental growth, morphology, substrate transport capacity, growth factor expression, and glucocorticoid exposure. We have used a pregnant sheep model in which the intrauterine environment has been perturbed by uterine carunclectomy (Cx). This procedure results in early restriction of placental growth and either the development of chronic fetal hypoxemia (PaO2≤17 mmHg) in late gestation or in compensatory placental growth and the maintenance of fetal normoxemia (PaO2>17 mmHg). Based on fetal PaO2, Cx, and Control ewes were assigned to either a normoxemic fetal group (Nx) or a hypoxemic fetal group (Hx) in late gestation, resulting in 4 groups. Cx resulted in a decrease in the volumes of fetal and maternal connective tissues in the placenta and increased placental mRNA expression of IGF2, vascular endothelial growth factor (VEGF), VEGFR‐2,ANGPT2, and TIE2. There were reduced volumes of trophoblast, maternal epithelium, and maternal connective tissues in the placenta and a decrease in placental GLUT1 and 11βHSD2 mRNA expression in the Hx compared to Nx groups. Our data show that early restriction of placental growth has effects on morphological and functional characteristics of the placenta in late gestation, independent of whether the fetus becomes hypoxemic. Similarly, there is a distinct set of placental changes that are only present in fetuses that were hypoxemic in late gestation, independent of whether Cx occurred. Thus, we provide further understanding of the different placental cellular and molecular mechanisms that are present in early placental restriction and in the emergence of later placental insufficiency.

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“…Human condition of intra-uterine growth restriction revealed no change in placental Glut1 (4) with differing results related to placental Glut3 concentrations (5,6,7). In contrast fetal growth restriction in a mouse caused by prenatal calorie restriction reduced placental Glut3 protein concentrations with diminution of trans-placental glucose transport (8).…”

mentioning

confidence: 92%

Prenatal caloric restriction enhances DNA methylation and MeCP2 recruitment with reduced murine placental glucose transporter isoform 3 expression

Ganguly¹,

Chen²,

Shin³

et al. 2014

The Journal of Nutritional Biochemistry

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Diminished trans-placental glucose transport plays an important role in prenatal calorie restriction induced reduction in fetal growth. Fetal growth restriction (FGR) has an impact in shaping the adult phenotype with trans-generational implications. To understand the mechanisms underlying prenatal calorie restriction induced trans-placental glucose transport, we examined epigenetic regulation of placental glucose transporter (Glut1 and Glut3) expression. We restricted calories by 50% in C57BL6 pregnant mice from gestational day 10 to 19 (CR; n=8) versus controls (CON; n=8) and observed a 50% diminution in placental Glut3 expression (p<0.05) with no effect on Glut1 expression by reverse transcription and quantitative real time PCR. CR enhanced DNA methylation of a CpG island situated ~1000 bp upstream from the transcriptional start site of the glut3 gene, with no such effect on the glut1 gene as assessed by methylation sensitive PCR and bisulfite sequencing. Chromatin immunoprecipitation (ChIP) assays demonstrated enhanced MeCP2 binding to the CpG island of the glut3 gene in response to CR versus CON (p<0.05). Sequential ChIP demonstrated that enhanced MeCP2 binding of the glut3-mCpG island enhanced histone deacetylase 2 (HDAC2) recruitment (p<0.05) but interfered with Sp1 binding (p<0.001) although not affecting Sp3 or Creb/pCreb interaction. We conclude that late gestation CR enhanced DNA methylation of placental glut3 gene. This epigenetic change augmented specific nuclear protein-DNA complex formation that was associated with prenatal CR induced reduction of placental glut3 expression and thereby trans-placental glucose transport. This molecular complex provides novel targets for developing therapeutic interventions aimed at reversing FGR.

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Placental glucose transporter 3 (GLUT3) is up-regulated in human pregnancies complicated by late-onset intrauterine growth restriction

Cited by 78 publications

References 48 publications

When two obese parents are worse than one! Impacts on embryo and fetal development

When two obese parents are worse than one! Impacts on embryo and fetal development

Early restriction of placental growth results in placental structural and gene expression changes in late gestation independent of fetal hypoxemia

Prenatal caloric restriction enhances DNA methylation and MeCP2 recruitment with reduced murine placental glucose transporter isoform 3 expression

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