Pregnancies in Diabetes and Obesity: The Capacity-Load Model of Placental Adaptation

Desoyé, Gernot; Wells, Jonathan C. K.

doi:10.2337/db20-1111

Cited by 17 publications

(13 citation statements)

References 76 publications

(86 reference statements)

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“…The transport of lipids across the placenta requires hydrolysis of maternal lipoproteins into fatty acids via the placental (PLP) and the endothelial (EL) lipases. The presence of GDM and obesity has been shown to increase the expression of EL (Desoye & Wells 2021). After hydrolysis the fatty acids are taken up by the placenta via fatty acid transport proteins 1 and 4, plasma membrane fatty acid binding protein and the fatty acid translocase CD36 (Herrera & Desoye 2016).…”

Section: Lipid Handlingmentioning

confidence: 99%

Programming of cardiometabolic health: the role of maternal and fetal hyperinsulinaemia

Hufnagel

Dearden

Fernandez‐Twinn

et al. 2022

Journal of Endocrinology

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Obesity and gestational diabetes during pregnancy have multiple short- and long-term consequences for both mother and child. One common feature of pregnancies complicated by maternal obesity and gestational diabetes is maternal hyperinsulinaemia, which has effects on the mother and her adaptation to pregnancy. Even though insulin does not cross the placenta insulin can act on the placenta as well affecting placental growth, angiogenesis and lipid metabolism. Obese and gestational diabetic pregnancies are often characterised by maternal hyperglycaemia resulting in exposure of the fetus to high levels of glucose, which freely crosses the placenta. This leads to stimulation of fetal b-cells and insulin secretion in the fetus. Fetal hyperglycaemia/hyperinsulinaemia has been shown to cause multiple complications in fetal development, such as altered growth trajectories, impaired neuronal and cardiac development and early exhaustion of the pancreas. These changes could increase the susceptibility of the offspring to develop cardiometabolic diseases later in life. In this review we aim to summarize and review the mechanisms by which maternal and fetal hyperinsulinaemia impact on (1) maternal health during pregnancy, (2) placental and fetal development, (3) offspring energy homeostasis and long-term cardio-metabolic health and (4) how interventions can alleviate these effects.

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Section: Lipid Handlingmentioning

confidence: 99%

Programming of cardiometabolic health: the role of maternal and fetal hyperinsulinaemia

Hufnagel

Dearden

Fernandez‐Twinn

et al. 2022

Journal of Endocrinology

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“…qPCR revealed significant (~95%) knockdown of Tlr4 in cKO microglia (Fig 3d). Excitingly, we saw significantly increased serotonin in male fetal forebrain and adult midbrain in mHFD No maternal data were available, so we assessed decidual triglyceride accumulation to use as a proxy for maternal weight, given that women with overweight/obesity exhibit triglyceride accumulation in the placenta 44 . Triglyceride levels trended higher in pregnancies with female fetuses, but there was no significant difference between triglyceride accumulation in decidua associated with male or female pregnancies (Extended Data Fig 5b).…”

Section: Mhfd Induces Tlr4-dependent Inflammation Driving Offspring Behavior Changesmentioning

confidence: 99%

Maternal diet disrupts the placenta-brain axis in a sex-specific manner

Ceasrine

Devlin

Bolton

et al. 2021

Preprint

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SUMMARYHigh maternal weight is associated with a number of detrimental outcomes in offspring, including increased susceptibility to neurological disorders such as anxiety, depression, and communicative disorders (e.g. autism spectrum disorders)1–4. Despite widespread acknowledgement of sex-biases in the prevalence, incidence, and age of onset of these disorders, few studies have investigated potential sex-biased mechanisms underlying disorder susceptibility. Here, we use a mouse model to demonstrate how maternal high-fat diet causes perinatal inflammation that influences sex-specific behavioral outcomes in offspring. In male high-fat diet offspring, increased macrophage toll like receptor 4 signaling results in excess phagocytosis of serotonin neurons in the developing dorsal raphe nucleus, decreasing serotonin bioavailability in the fetal and adult brain. Bulk sequencing from a large cohort of matched first trimester human fetal brain, placenta, and maternal decidua samples reveals sex-specific transcriptome-wide changes in placenta and brain tissue. Further, we find that fetal brain serotonin is significantly negatively correlated with maternal triglyceride accumulation (a proxy for dietary fat content) in male pregnancies only. These findings uncover a fundamental mechanism through which maternal diet may increase offspring susceptibility for neuropsychiatric disorder development.

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“…The placenta plays a central role in regulating the fetal environment [ 16 ]. It not only controls the exchange of nutrients, gasses, and wastes between the maternal and fetal circulations, but is also an important source of hormones that regulate fetal development.…”

Section: Introductionmentioning

confidence: 99%

Maternal Metabolic State and Fetal Sex and Genotype Modulate Methylation of the Serotonin Receptor Type 2A Gene (HTR2A) in the Human Placenta

et al. 2022

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The serotonin receptor 2A gene (HTR2A) is a strong candidate for the fetal programming of future behavior and metabolism. Maternal obesity and gestational diabetes mellitus (GDM) have been associated with an increased risk of metabolic and psychological problems in offspring. We tested the hypothesis that maternal metabolic status affects methylation of HTR2A in the placenta. The prospective study included 199 pairs of mothers and healthy full-term newborns. Genomic DNA was extracted from feto-placental samples and analyzed for genotypes of two polymorphisms (rs6311, rs6306) and methylation of four cytosine residues (−1665, −1439, −1421, −1224) in the HTR2A promoter region. Placental HTR2A promoter methylation was higher in male than female placentas and depended on both rs6311 and rs6306 genotypes. A higher maternal pre-gestational body mass index (pBMI) and, to a lesser extent, diagnosis of GDM were associated with reduced HTR2A promoter methylation in female but not male placentas. Higher pBMI was associated with reduced methylation both directly and indirectly through increased GDM incidence. Tobacco use during pregnancy was associated with reduced HTR2A promoter methylation in male but not female placentas. The obtained results suggest that HTR2A is a sexually dimorphic epigenetic target of intrauterine exposures. The findings may contribute to a better understanding of the early developmental origins of neurobehavioral and metabolic disorders associated with altered HTR2A function.

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Pregnancies in Diabetes and Obesity: The Capacity-Load Model of Placental Adaptation

Cited by 17 publications

References 76 publications

Programming of cardiometabolic health: the role of maternal and fetal hyperinsulinaemia

Programming of cardiometabolic health: the role of maternal and fetal hyperinsulinaemia

Maternal diet disrupts the placenta-brain axis in a sex-specific manner

Maternal Metabolic State and Fetal Sex and Genotype Modulate Methylation of the Serotonin Receptor Type 2A Gene (HTR2A) in the Human Placenta

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