Irving Aye

University of Cambridge | Cam · Department of Obstetrics & Gynaecology

Context Stretch of the myometrium promotes its contractility and is believed to contribute to the control of parturition at term and to the increased risk of preterm birth in multiple pregnancies. Objective To determine the effects of the putative oxytocin receptor (OTR) inverse agonist retosiban on (i) the contractility of human myometrial explan...

Significance Obesity and metabolic syndrome may, in part, originate in fetal life. In particular, babies of mothers with obesity and/or gestational diabetes mellitus (GDM) are often large at birth and have increased adiposity, which predisposes them to the development of metabolic disease later in life. Maternal obesity and GDM are typically associ...

Obese pregnant women have increased levels of pro-inflammatory cytokines in maternal circulation and placental tissues. However, the pathways contributing to placental inflammation in obesity are largely unknown. We tested the hypothesis that maternal body mass index (BMI) was associated with elevated pro-inflammatory cytokines in maternal and feta...

Maternal adiponectin levels are inversely correlated with birth weight, and adiponectin infusion in pregnant mice down-regulates placental nutrient transporters and decreases fetal growth. In contrast to the insulin sensitizing effects in adipose tissue and muscle, adiponectin inhibits insulin signaling in the placenta. However the molecular mechan...

Oxidized cholesterol metabolites (oxysterols) promote inflammation in a variety of cell types and are thought to be involved in a number of disease pathologies. Oxysterol concentrations are increased in pregnancy, together with systemic oxidative stress and inflammation. We tested the hypothesis that oxysterols 25-hydroxycholesterol (25-OHC) and 7-...

Context Circulating adiponectin levels are decreased in pregnant women with obesity or gestational diabetes, and this is believed to contribute to the insulin resistance and increased risk of fetal overgrowth associated with these conditions. However, the molecular mechanisms regulating adiponectin secretion from maternal adipose tissues in pregnan...

Fetal sex differences play an important role in the pathophysiology of several placenta related pregnancy complications. We previously reported that the maternal circulating level of a polyamine metabolite was altered in a fetal sex-specific manner, and was associated with pre-eclampsia and fetal growth restriction. Here we show that placental poly...

In pregnancy, adiponectin serves as an endocrine link between maternal adipose tissue, placental function and fetal growth, with low adiponectin promoting placental function and fetal growth. Circulating adiponectin levels are decreased in obese pregnant women and in gestational diabetes, which is believed to contribute to the insulin resistance an...

The placenta is a highly metabolically active organ fulfilling the bioenergetic and biosynthetic needs to support its own rapid growth and that of the fetus. Placental metabolic dysfunction is a common occurrence in preeclampsia although its causal relationship to the pathophysiology is unclear. At the outset, this may simply be seen as an “engine...

Preeclampsia and fetal growth restriction (FGR) are major causes of the more than 5 million perinatal and infant deaths occurring globally each year, and both are associated with placental dysfunction. The risk of perinatal and infant death is greater in males, but the mechanisms are unclear. We studied data and biological samples from the Pregnanc...

Group 2 innate lymphoid cells (ILC2s) adapt to tissue physiology and contribute to immunity, inflammatory pathology and metabolism. We show that mouse uterine ILC2s have a heightened type-2 gene signature and expand during pregnancy. Indeed, maternal ILC2s promote fetal growth and protect against fetal mortality upon systemic endotoxin challenge. A...

Context: Stretch of the myometrium promotes its contractility and is believed to contribute to the control of parturition at term and to the increased risk of preterm birth in multiple pregnancies. Objective: To determine the effects of the putative oxytocin receptor (OTR) inverse agonist retosiban on (i) the contractility of human myometrial expla...

Fetal growth restriction is a major determinant of perinatal morbidity and mortality. Screening for fetal growth restriction is a key element of prenatal care but it is recognized to be problematic. Screening using clinical risk assessment and targeting ultrasound to high-risk women is the standard of care in the United States and United Kingdom, b...

Fetal growth restriction is a major determinant of perinatal morbidity and mortality. Screening for fetal growth restriction is a key element of prenatal care but it is recognized to be problematic. Screening using clinical risk assessment and targeting ultrasound to high-risk women is the standard of care in the United States and United Kingdom, b...

In his Letter to the Editor, Carbillon (1) maintains that our mouse model of maternal obesity leading to fetal overgrowth (2) may not be relevant for the clinical condition because the fetal/placental weight ratio was not decreased, as is sometimes found in obese pregnant women. We disagree with Carbillon’s (1) assessment.

Maternal obesity and gestational diabetes mellitus (GDM) increase the risk of delivering infants that are large for gestational age with greater adiposity, who are prone to the development of metabolic disease in childhood and beyond. These maternal conditions are also associated with increased levels of the proinflammatory cytokine TNF-α in matern...

System L transporters LAT1 (SLC7A5) and LAT2 (SLC7A8) mediate the uptake of large, neutral amino acids in the human placenta. Many System L substrates are essential amino acids, thus representing crucial nutrients for the growing fetus. Both LAT isoforms are expressed in the human placenta, but the relative contribution of LAT1 and LAT2 to placenta...

Maternal obesity increases the risk of health complications in both the mother and the infant.In turn, the offspring of obese mothers are inclined to develop obesity, cardiovascular disease, and type 2 diabetes as adults, establishing a vicious cycle of metabolic disease.Obese mothers exhibit dyslipidemia, inflammation, and insulin resistance, fact...

The human placenta, in addition to its roles as a nutrient transfer and endocrine organ, functions as a selective barrier to protect the fetus against the harmful effects of exogenous and endogenous toxins. Members of the ATP-binding cassette (ABC) family of transport proteins limit the entry of xenobiotics into the fetal circulation via vectorial...

Sphingolipid mediators such as ceramide are pleiotropic regulators of cellular growth, differentiation and apoptosis. We investigated the role of ceramide biosynthesis, metabolism and actions in term human cytotrophoblasts syncytialized over 7 days in culture. Intracellular C16 ceramide levels increased modestly after 3 days in culture, then declin...

Sphingosine and sphingosine-1-phosphate (S1P) are involved in regulating cell differentiation. This study postulated that changes in sphingolipid biosynthesis and metabolism are important in trophoblast syncytialization and therefore examined the production, metabolism and actions of sphingosine and S1P during spontaneous trophoblast differentiatio...

ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 mediate the efflux of cholesterol and other sterols. Both transporters are expressed on the fetal capillaries of the placenta and are involved in maternal-to-fetal cholesterol delivery. In this study, we report that ABCA1 and ABCG1 are also present on the syncytiotrophoblast, the maternal faci...

Members of the ATP-binding cassette (ABC) family of membrane-bound transporters are involved in multiple aspects of transport and redistribution of various lipids and their conjugates. Most ABC transporters localize to the plasma membrane; some are associated with liquid-ordered cholesterol-/sphingolipid-rich microdomains, and to a lesser extent th...

Placental ATP-binding cassette (ABC) transporters limit fetal exposure to xenobiotics by regulating transplacental passage into the fetal circulation; their expression and function in fetal membranes, however, has not been studied. In the present study the expression, localisation and function of ABC transporters in human amnion was examined to exp...