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Molecular heterogeneity of endothelial cells underlies their highly specialized functions during changing physiological conditions within diverse vascular beds. For example, placental spiral arteries (SAs) undergo remarkable remodeling to meet the ever-growing demands of the fetus--a process which is deficient in preeclampsia. The extent to which maternal endothelial cells coordinate with immune cells and pregnancy hormones to promote SA remodeling remains largely unknown. Here we found that remodeled SAs expressed the lymphatic markers PROX1, LYVE1, and VEGFR3, mimicking lymphatic identity. Uterine natural killer (uNK) cells, which are required for SA remodeling and secrete VEGFC, were both sufficient and necessary for VEGFR3 activation in vitro and in mice lacking uNK cells, respectively. Using [Flt4.sup.Chy/+] mice with kinase inactive VEGFR3 and [Vegfc.sup.fl/fl] Vav1-Cre mice, we demonstrated that SA remodeling required VEGFR3 signaling, and that disrupted maternal VEGFR3 signaling contributed to late-gestation fetal growth restriction. Collectively, we identified a novel instance of lymphatic mimicry by which maternal endothelial cells promote SA remodeling, furthering our understanding of the vascular heterogeneity employed for the mitigation of pregnancy complications such as fetal growth restriction and preeclampsia., Introduction Endothelial cells (ECs) lining the vasculature display a large degree of phenotypic variation and molecular heterogeneity, reflecting the vastly different environmental milieus and functions of target end organs (1, [...]

Adequate thiamin levels are crucial for optimal health through maintenance of homeostasis and viability of metabolic enzymes, which require thiamine as a co-factor. Thiamin deficiency occurs during pregnancy when the dietary intake is inadequate or excessive alcohol is consumed. Thiamin deficiency leads to brain dysfunction because thiamin is involved in the synthesis of myelin and neurotransmitters (e.g., acetylcholine, [gamma]-aminobutyric acid, glutamate), and its deficiency increases oxidative stress by decreasing the production of reducing agents. Thiamin deficiency also leads to neural membrane dysfunction, because thiamin is a structural component of mitochondrial and synaptosomal membranes. Similarly, in-utero exposure to alcohol leads to fetal brain dysfunction, resulting in negative effects such as fetal alcohol spectrum disorder (FASD). Thiamin deficiency and prenatal exposure to alcohol could act synergistically to produce negative effects on fetal development; however, this area of research is currently under-studied. This minireview summarizes the evidence for the potential role of thiamin deficiency in fetal brain development, with or without prenatal exposure to alcohol. Such evidence may influence the development of new nutritional strategies for preventing or mitigating the symptoms of FASD. Key words: thiamin, brain, fetus, alcohol, fetal alcohol spectrum disorder. Des niveaux adequats de thiamine sont essentiels a une sante optimale en maintenant l'homeostasie et la viabilite des enzymes metaboliques qui utilisent la thiamine comme cofacteur. La deficience en thiamine durant la grossesse survient lorsque l'apport par la diete est insuffisant ou qu'une quantite excessive d'alcool est consommee. La deficience en thiamine mene a une dysfonction cerebrale a cause de son implication dans la synthese de la myeline et des neurotransmetteurs (p.ex. l'acetylcholine, l'acide 32 [gamma]-aminobutyrique, le glutamate) et elle accroit le stress oxydant en diminuant la production d'agents reducteurs. La deficience mene aussi au dysfonctionnement de la membrane neurale car la thiamine est une composante structurale des membranes mitochondriales et synaptiques. De la meme facon, l'exposition a l'alcool in utero provoque une dysfonction du cerveau foetal qui resulte en des effets indesirables tels les troubles du spectre de l'alcoolisation foetale (TSAF). Les consequences indesirables de la deficience en thiamine et de l'exposition prenatale a l'alcool pourraient resulter de leur action synergique sur le developpement foetal, mais ce domaine de recherche est sous-etudie. Cette synthese resume les preuves du role potentiel de la deficience en thiamine dans le developpement du cerveau foetal avec ou sans exposition prenatale a l'alcool. De telles preuves pourraient influencer le developpement de nouvelles strategies nutritionnelles pour prevenir ou attenuer les symptomes des TSAF. [Traduit par la Redaction] Mots-cles: thiamine, cerveau, foetus, alcool, troubles du spectre de l'alcoolisation foetale., Introduction Maternal abuse of alcohol and its effect on the developing fetus has been widely studied for several decades. Prenatal alcohol consumption is associated with fetal alcohol spectrum disorder (FASD), [...]

Skeletal muscle is critical for mobility and many metabolic functions integral to survival and long-term health. Alcohol can affect skeletal muscle physiology and metabolism, which will have immediate and long-term consequences on health. While skeletal muscle abnormalities, including morphological, biochemical, and functional impairments, are well-documented in adults that excessively consume alcohol, there is a scarcity of information about the skeletal muscle in the offspring prenatally exposed to alcohol ('prenatal alcohol exposure'; PAE). This minireview examines the available studies addressing skeletal muscle abnormalities due to PAE. Growth restriction, fetal alcohol myopathy, and abnormalities in the neuromuscular system, which contribute to deficits in locomotion, are some direct, immediate consequences of PAE on skeletal muscle morphology and function. Long-term health consequences of PAE-related skeletal abnormalities include impaired glucose metabolism in the skeletal muscle, resulting in glucose intolerance and insulin resistance, leading to an increased risk of type 2 diabetes. In general, there is limited information on the morphological, biochemical, and functional features of skeletal abnormalities in PAE offspring. There is a need to understand how PAE affects muscle growth and function at the cellular level during early development to improve the immediate and long-term health of offspring suffering from PAE. Key words: muscle fiber, fetal alcohol myopathy, cytoskeleton proteins, amino acids, insulin resistance. Le muscle squelettique est un element cle de la mobilite et de plusieurs fonctions metaboliques necessaires a la survie et a la sante a long terme. L'alcool peut affecter la physiologie et le metabolisme du muscle squelettique, ce qui aura des consequences immediates et a long terme sur la sante. Alors que les anomalies du muscle squelettique, qui comprennent des deficits morphologiques, biochimiques et fonctionnels, sont bien documentees chez les adultes qui abusent d'alcool, l'information sur le muscle squelettique d'enfants soumis a une exposition prenatale a l'alcool (EPA) est rare. Cette synthese examine les etudes disponibles qui portent sur les anomalies du muscle squelettique provoquees par l'EPA. Le retard de croissance, la myopathie alcoolique foetale et les anomalies du systeme neuromusculaire qui contribuent aux problemes de locomotion constituent quelques unes des consequences directes et immediates de l'EPA sur la morphologie et la fonction du muscle squelettique. Les consequences sur lasante a long terme des anomalies dumuscle squelettique lieesal'EPA comprennent une diminutiondumetabolismedu glucose dans lemuscle, resultantenune intoleranceau glucose etune resistance al'insuline qui menent a un risque accru de developper un diabete de type 2. En general, l'information sur les caracteristiques morphologiques, biochimiques et fonctionnelles des anomalies squelettiques des enfants soumis a une EPA est limitee. Il est necessaire de comprendre comment l'EPA affecte la croissance et la fonction du muscle au niveau cellulaire durant le developpement precoce afin d'ameliorer la sante immediate et a long terme des enfants soumis a une EPA. [Traduit par la Redaction] Mots-cles : fibre musculaire, myopathie alcoolique foetale, proteines du cytosquelette, acides amines, resistance a l'insuline., Introduction Skeletal muscle, comprising about 30% of the body mass in the neonate, is critical for mobility and many metabolic functions integral tosurvival and long-term health (Davis and Fiorotto 2009; [...]

Obesity during pregnancy is a major health problem in the United States. In this issue of the JCI, Most et al. fill an important gap in our understanding of energy homeostasis in pregnancy. The researchers measured energy intake, energy expenditure, and body composition in obese pregnant women. They demonstrated that energy intake need not increase in order for obese women to gain the recommended amounts of weight during pregnancy. Additionally, all of the gestational weight gain scenarios (inadequate, recommended, or excess) resulted in similar maternal and fetal perinatal outcomes. This evidence should guide new recommendations on this important topic., Previous weight gain guidelines The Institute of Medicine (IOM) guidelines, set in 2009, recommended that women with obesity gain 11 to 20 pounds at a rate of 0.5 pounds/week during [...]