Mild Gestational Hyperglycemia in Rat Induces Fetal Overgrowth and Modulates Placental Growth Factors and Nutrient Transporters Expression

Cisse, Ouma; Fajardy, I.; Dickes-Coopman, Anne; Moitrot, Emmanuelle; Montel, Valérie; Deloof, Sylvie; Rousseaux, J.; Vieau, Didier; Laborie, Christine

doi:10.1371/journal.pone.0064251

Cited by 12 publications

(8 citation statements)

References 50 publications

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“…Macrosomic GDM offspring display increased body weight, hyperinsulinemia and reduced glucose tolerance as adults (51). Additionally, maternal hyperglycemia has significant effects on placental growth and function (53), which may explain the alterations to birth weight commonly reported in GDM offspring. (Figure 1).…”

Section: Maternal Glucose Levelsmentioning

confidence: 99%

Early life origins of metabolic disease: Developmental programming of hypothalamic pathways controlling energy homeostasis

Dearden

Ozanne

2015

Frontiers in Neuroendocrinology

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A wealth of animal and human studies demonstrate that perinatal exposure to adverse metabolic conditions - be it maternal obesity, diabetes or under-nutrition - results in predisposition of offspring to develop obesity later in life. This mechanism is a contributing factor to the exponential rise in obesity rates. Increased weight gain in offspring exposed to maternal obesity is usually associated with hyperphagia, implicating altered central regulation of energy homeostasis as an underlying cause. Perinatal development of the hypothalamus (a brain region key to metabolic regulation) is plastic and sensitive to metabolic signals during this critical time window. Recent research in non-human primate and rodent models has demonstrated that exposure to adverse maternal environments impairs the development of hypothalamic structure and consequently function, potentially underpinning metabolic phenotypes in later life. This review summarizes our current knowledge of how adverse perinatal environments program hypothalamic development and explores the mechanisms that could mediate these effects.

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Section: Maternal Glucose Levelsmentioning

confidence: 99%

Early life origins of metabolic disease: Developmental programming of hypothalamic pathways controlling energy homeostasis

Dearden

Ozanne

2015

Frontiers in Neuroendocrinology

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“…Placental lipid transport capacity is also increased in rat dams that are diabetic for 1 week prior to pregnancy (increase in placental lipoprotein lipase); however, the expression of Igf2 and the IGF signalling machinery is decreased and the expression of GLUT1/Glut1/Slc2a1 reduced in association with a more minor increase in fetal weight (by 5%) (Cisse et al . ). Genetically inducing maternal insulin insensitivity by a global heterozygous deficiency in PI3K‐p110α signalling capacity in the mouse dam is associated with improved placental Lz development (larger surface area and thinner barrier to diffusion), but reduced glucose transport and expression of nutrient ( GLUT1/Glut1/Slc2a1, SNAT1/Snat1/Slc38a1, SNAT2/Snat2/Slc38a2 ) and prolactin‐related family genes near term (Sferruzzi‐Perri et al .…”

Section: Introductionmentioning

confidence: 97%

Placental phenotype and the insulin‐like growth factors: resource allocation to fetal growth

Sferruzzi‐Perri

Sandovici²,

Constância³

et al. 2017

The Journal of Physiology

140

128

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The placenta is the main determinant of fetal growth and development in utero. It supplies all the nutrients and oxygen required for fetal growth and secretes hormones that facilitate maternal allocation of nutrients to the fetus. Furthermore, the placenta responds to nutritional and metabolic signals in the mother by altering its structural and functional phenotype, which can lead to changes in maternal resource allocation to the fetus. The molecular mechanisms by which the placenta senses and responds to environmental cues are poorly understood. This review discusses the role of the insulin-like growth factors (IGFs) in controlling placental resource allocation to fetal growth, particularly in response to adverse gestational environments. In particular, it assesses the impact of the IGFs and their signalling machinery on placental morphogenesis, substrate transport and hormone secretion, primarily in the laboratory species, although it draws on data from human and other species where relevant. It also considers the role of the IGFs as environmental signals in linking resource availability to fetal growth through changes in the morphological and functional phenotype of the placenta. As altered fetal growth is associated with increased perinatal morbidity and mortality and a greater risk of developing adult-onset diseases in later life, understanding the role of IGFs during pregnancy in regulating placental resource allocation to fetal growth is important for identifying the mechanisms underlying the developmental programming of offspring phenotype by suboptimal intrauterine growth.

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“…However, placental expression of amino acid transporters was unchanged in both female and male fetuses in aged, compared to young dams. Furthermore, in both female and male fetuses, placental expression of glucose transporters ( Slc2a1 and Slc2a3 ) was not compromised by advanced maternal age, unlike other adverse maternal conditions in rodents and women, such as excess glucocorticoids, malnutrition, obesity, hyperglycemia and hypoxia 41–47 . Interestingly, placental abundance of VEGF was diminished in both female and male pups from aged dams.…”

Section: Discussionmentioning

confidence: 96%

Advanced maternal age compromises fetal growth and induces sex-specific changes in placental phenotype in rats

Napso

Hung

Davidge

et al. 2019

Sci Rep

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Advanced maternal age is associated with an increased risk of pregnancy complications. It programmes sex-specific cardiovascular dysfunction in rat offspring, however the intrauterine mechanisms involved remain unknown. This study in the rat assessed the impact of advanced maternal age on placental phenotype in relation to the growth of female and male fetuses. We show that relative to young (3–4 months) dams, advanced maternal age (9.5–10 months) compromises growth of both female and male fetuses but affects the placental phenotype sex-specifically. In placentas from aged versus young dams, the size of the placental transport and endocrine zones were increased and expression of Igf2 (+41%) and placental lactogen (Prl3b1: +59%) genes were upregulated in female, but not male fetuses. Placental abundance of IGF2 protein also decreased in the placenta of males only (−95%). Moreover, in placentas from aged versus young dams, glucocorticoid metabolism (11β-hsd2: +63% and 11β-hsd1: −33%) was higher in females, but lower in males (11β-hsd2: −50% and 11β-hsd1: unaltered). There was however, no change in the placental abundance of 11β-HSD2 protein in aged versus young dams regardless of fetal sex. Levels of oxidative stress in the placenta were increased in female and male fetuses (+57% and +90%, respectively) and apoptosis increased specifically in the placenta of males from aged rat dams (+700%). Thus, advanced maternal age alters placental phenotype in a sex-specific fashion. These sexually-divergent changes may play a role in determining health outcomes of female and male offspring of aged mothers.

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Mild Gestational Hyperglycemia in Rat Induces Fetal Overgrowth and Modulates Placental Growth Factors and Nutrient Transporters Expression

Cited by 12 publications

References 50 publications

Early life origins of metabolic disease: Developmental programming of hypothalamic pathways controlling energy homeostasis

Early life origins of metabolic disease: Developmental programming of hypothalamic pathways controlling energy homeostasis

Placental phenotype and the insulin‐like growth factors: resource allocation to fetal growth

Advanced maternal age compromises fetal growth and induces sex-specific changes in placental phenotype in rats

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