Avaliação da concentração de vitamina A materna e de neonatos prematuros e a termo

Vitamin A is an essential nutrient for many physiological processes such as growth and development, so that their adequate nutritional state is essential during pregnancy and lactation. Lactating women and children in breastfeeding are considered risk groups for vitamin A deficiency and some factors may increase the risk of vitamin A deficiency, such as prematurity. The aim of this work was to evaluate the vitamin A concentration in preterm and term lactating women and newborns by determination of retinol in maternal serum, umbilical cord serum and breast milk collected until 72 hours postpartum. 182 mothers were recruited and divided into preterm group (GPT; n = 118) and term group (GT, n = 64). In preterm group were also analyzed transition milk (7th-15th day; n = 68) and mature milk (30th-55th day; n = 46) samples. Retinol was analyzed by high-performance liquid chromatography (HPLC). Maternal retinol concentration in serum was 48.6 ± 12.3 µg/dL in GPT and 42.8 ± 16.3 µg/dL in the GT (p <0.01). Cord serum retinol was 20.4 ± 7.4 µg/dL in GPT and 23.2 ± 7.6 µg/dL in GT (p> 0.05). Among newborns, 43% of premature and 36% of term had low levels of serum retinol in umbilical cord (<20 µg/dL). In colostrum, the retinol in preterm and term groups had an average of 100.8 ± 49.0 µg/dL and 127.5 ± 65.1 µg/dL, respectively (p <0.05). The retinol average in preterm milk increased to 112.5 ± 49.7 µg/dL in transition phase and decreased to 57.2 ± 23.4 µg/dL in mature milk, differing significantly in all stages (p <0.05). When comparing with the recommendation of vitamin A intake (400 µg/day) GT colostrum reached the recommendation for infants, but in GPT the recommendation was not achieved at any stage. Mothers of premature infants had higher serum retinol than mothers at term; however, this was not reflected in serum retinol of umbilical cord, since premature had lower concentration of retinol. Such condition can be explained due to lower maternal physiological hemodilution and placental transfer of retinol to the fetus during preterm gestation. Comparison of retinol in colostrum showed lower concentrations in GPT; however the transition phase there was a significant increase of retinol content released by the mammary gland of preterm mothers. This situation highlights a specific physiological adaptation of prematurity, likely to more contribute to formation of hepatic reserves of retinol in premature infants.

Evidence of positive selection associated with placental loss in tiger sharks

Acknowledgements We thank staff at the Cape Eleuthera Institute for assistance in the field, Dominique Barthelemy and Jean Goasdoue for providing samples, and Helen Hipperson for assistance in the lab.

Placental vascularity and markers of angiogenesis in relation to prenatal growth status in overnourished adolescent ewes

Acknowledgments Supported by the Wellcome Trust project grant 088208 (DJC), Wellbeing of Women research training fellowship 318 (DJC), Scottish Government Work package 4.2 (JMW, JSM and RPA), National Institute for Health Research University College London Hospitals Biomedical Research Centre (ALD) and Hatch ProjectND01748 (DAR).

Developmental and molecular aberrations associated with deterioration of oocytes during FSH-receptor deficiency

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Dysregulation of placental cystathionine-β-synthase promotes fetal growth restriction

Fetal growth restriction (FGR) is characterized by the birth weight and body mass below the tenth percentile for gestational age. FGR is a major cause of perinatal morbidity and mortality and babies born with FGR are prone to develop cardiovascular diseases later in life. The underlying pathology of FGR is inadequate placental transfer of nutrients from mother to fetus, which can be caused by placental insufficiency. Hydrogen sulfide (H2S), a gaseous messenger is produced endogenously by cystathionine-lyase (Cth), cystathionine-β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST), which are present in human placenta. Recently, we demonstrated that the dysregulation of H2S/Cth pathway is associated with preeclampsia and blockade of CSE activity induces preeclampsia-like condition in pregnant mice. We hypothesized that defect in H2S pathways promote FGR and H2S donor restores fetal growth in mice where CBS or CSE activity has been compromised. Western blotting and qPCR revealed that placental CBS expressions were significantly reduced in women with FGR. ELISA analysis showed reduced placental growth factor production (PlGF) from first trimester (8–12 weeks gestation) human placental explants following inhibition of CBS activity by aminooxyacetic acid (AOA). Administration of AOA to pregnant mice had no effects on blood pressure, but caused fetal growth restriction. This was associated with reduced PlGF production. Histological analysis revealed a reduction in the placental junction zone, within which trophoblast giant cells and glycogen cells were less prominent in CBS inhibitor treated mice. These results imply that placental CBS is required for placental development and that dysregulation of CBS activity may contribute to the pathogenesis of FGR but not preeclampsia.

Dysregulation of placental cystathionine-β-synthase impact on fetal growth restriction

INTRODUCTION: Fetal growth restriction (FGR), which causes perinatal morbidity and mortality, is characterized by birth weight and body mass being below 10th percentile for gestational age. FGR babies are prone to develop cardiovascular diseases later in life. Inadequate placental transfer of nutrients from mother to fetus due to placental insufficiency is considered the underlying cause of FGR. Recently, we demonstrated that blockade of cystathionine-γ-lyase (CSE) activity induces preeclampsia-like condition in pregnant mice. We hypothesized that defect in cystathionine-β-synthase (CBS) / H2S pathway may promote FGR. METHODS: Placental CBS expressions were determined in women with FGR (n=9) and normal controls (n=14) by Western blotting and real-time qPCR. ELISA was used to determine angiogenic factors levels in plasma and first-trimester (8–12 weeks gestation) human placental explants. Time pregnant mice were treated with CBS inhibitor, aminooxyacetic acid (AOA). Mean arterial blood pressure (MBP), histological assessments of placenta and embryos were performed. RESULTS: Placental CBS expressions were significantly reduced in women with FGR. Inhibition of CBS activity by AOA reduced PlGF production from first-trimester human placental explants, Administration of AOA to pregnant mice had no effects on blood pressure, but caused fetal growth restriction, which was associated with reduced placental PlGF production. Histological analysis revealed a reduction in the placental junction zone, within which trophoblast giant cells and glycogen cells were less prominent in CBS inhibitor-treated animals. Furthermore, H2S donor GYY4137 treatment restored fetal growth in pregnant mice exposed to high level of sFlt-1. CONCLUSIONS: These results imply that placental CBS is required for placental development and that dysregulation of CBS activity may contribute to the pathogenesis of FGR but not preeclampsia opening up the therapeutic potentials of H2S therapy in this condition.

Placental contribution to the origins of sexual dimorphism in health and diseases: sex chromosomes and epigenetics

Sex differences occur in most non-communicable diseases, including metabolic diseases, hypertension, cardiovascular disease, psychiatric and neurological disorders and cancer. In many cases, the susceptibility to these diseases begins early in development. The observed differences between the sexes may result from genetic and hormonal differences and from differences in responses to and interactions with environmental factors, including infection, diet, drugs and stress. The placenta plays a key role in fetal growth and development and, as such, affects the fetal programming underlying subsequent adult health and accounts, in part for the developmental origin of health and disease (DOHaD). There is accumulating evidence to demonstrate the sex-specific relationships between diverse environmental influences on placental functions and the risk of disease later in life. As one of the few tissues easily collectable in humans, this organ may therefore be seen as an ideal system for studying how male and female placenta sense nutritional and other stresses, such as endocrine disruptors. Sex-specific regulatory pathways controlling sexually dimorphic characteristics in the various organs and the consequences of lifelong differences in sex hormone expression largely account for such responses. However, sex-specific changes in epigenetic marks are generated early after fertilization, thus before adrenal and gonad differentiation in the absence of sex hormones and in response to environmental conditions. Given the abundance of X-linked genes involved in placentogenesis, and the early unequal gene expression by the sex chromosomes between males and females, the role of X- and Y-chromosome-linked genes, and especially those involved in the peculiar placenta-specific epigenetics processes, giving rise to the unusual placenta epigenetic landscapes deserve particular attention. However, even with recent developments in this field, we still know little about the mechanisms underlying the early sex-specific epigenetic marks resulting in sex-biased gene expression of pathways and networks. As a critical messenger between the maternal environment and the fetus, the placenta may play a key role not only in buffering environmental effects transmitted by the mother but also in expressing and modulating effects due to preconceptional exposure of both the mother and the father to stressful conditions.

Developmental and molecular aberrations associated with deterioration of oocytes during FSH-receptor deficiency

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Risk Factors for Maternal Vitamin D Deficiency within the United Arab Emirates

Introduction: Vitamin D deficiency during pregnancy is a public health problem and it has been associated with negative pregnancy outcomes for both mothers and infants. Aim: To estimate the prevalence of vitamin D deficiency in pregnant women in the United Arab Emirates (UAE) and to identify the contribution of risk factors to the 25(OH)D levels. Methods: It is a cross-sectional study in which vitamin D levels of 1088 adult pregnant women were assessed. Information on vitamin D intake was available in a sub-sample of 266 women. Results: The mean serum 25(OH)D was 26.2 nmol/L (95% CI 25.2-27.1 range 5-129.1 nmol/L) with 69% of women being vitamin D deficient (<30 nmol/L). In the bivariate analysis, showed that no predictors could have been indicated as no values exceeded significance (p<0.2). Stepwise multiple linear regression analysis could not be applied to identify predictors of vitamin D levels as no values exceeded p=0.2. Conclusion: Due to the high prevalence of vitamin deficiency in UAE, there is an urge for interventions focusing on supplementation, fortification and diet diversity for preventing health consequences during a critical period of development.

Phosphate Deficiency Induces the Jasmonate Pathway and Enhances Resistance to Insect Herbivory.

During their life cycle, plants are typically confronted by simultaneous biotic and abiotic stresses. Low inorganic phosphate (Pi) is one of the most common nutrient deficiencies limiting plant growth in natural and agricultural ecosystems, while insect herbivory accounts for major losses in plant productivity and impacts ecological and evolutionary changes in plant populations. Here, we report that plants experiencing Pi deficiency induce the jasmonic acid (JA) pathway and enhance their defense against insect herbivory. Pi-deficient Arabidopsis (Arabidopsis thaliana) showed enhanced synthesis of JA and the bioactive conjugate JA-isoleucine, as well as activation of the JA signaling pathway, in both shoots and roots of wild-type plants and in shoots of the Pi-deficient mutant pho1 The kinetics of the induction of the JA signaling pathway by Pi deficiency was influenced by PHOSPHATE STARVATION RESPONSE1, the main transcription factor regulating the expression of Pi starvation-induced genes. Phenotypes of the pho1 mutant typically associated with Pi deficiency, such as high shoot anthocyanin levels and poor shoot growth, were significantly attenuated by blocking the JA biosynthesis or signaling pathway. Wounded pho1 leaves hyperaccumulated JA/JA-isoleucine in comparison with the wild type. The pho1 mutant also showed an increased resistance against the generalist herbivore Spodoptera littoralis that was attenuated in JA biosynthesis and signaling mutants. Pi deficiency also triggered increased resistance to S. littoralis in wild-type Arabidopsis as well as tomato (Solanum lycopersicum) and Nicotiana benthamiana, revealing that the link between Pi deficiency and enhanced herbivory resistance is conserved in a diversity of plants, including crops.

Lymphatic porosity as a consequence of complex vitamin B deficiency in the rat

Lymphatic porosity was produced by feeding rats a diet, lacking from the vitamins of the B group. Coumarintroxerutin (Venalot®) treatment has been found to prevent this abnormality. Pathophysiologic and therapeutic implications of these findings are discussed. © 1973 S. Karger AG, Basel.

Congenital adrenal hyperplasia: focus on the molecular basis of 21-hydroxylase deficiency

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by defects in one of several steroidogenic enzymes involved in the synthesis of cortisol from cholesterol in the adrenal glands. More than 90% of cases are caused by 21-hydroxylase deficiency, and the severity of the resulting clinical symptoms varies according to the level of 21-hydroxylase activity. 21-Hydroxylase deficiency is usually caused by mutations in the CYP21A2 gene, which is located on the RCCX module, a chromosomal region highly prone to genetic recombination events that can result in a wide variety of complex rearrangements, such as gene duplications, gross deletions and gene conversions of variable extensions. Molecular genotyping of CYP21A2 and the RCCX module has proved useful for a more accurate diagnosis of the disease, and prenatal diagnosis. This article summarises the clinical features of 21-hydroxylase deficiency, explains current understanding of the disease at the molecular level, and highlights recent developments, particularly in diagnosis.

Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development.

In the current study, we have developed a magnetic resonance imaging-based method for non-invasive detection of complement activation in placenta and foetal brain in vivo in utero. Using this method, we found that anti-complement C3-targeted ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles bind within the inflamed placenta and foetal brain cortical tissue, causing a shortening of the T2* relaxation time. We used two mouse models of pregnancy complications: a mouse model of obstetrics antiphospholipid syndrome (APS) and a mouse model of preterm birth (PTB). We found that detection of C3 deposition in the placenta in the APS model was associated with placental insufficiency characterised by increased oxidative stress, decreased vascular endothelial growth factor and placental growth factor levels and intrauterine growth restriction. We also found that foetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased neurodegeneration in the mouse model of APS and in the PTB model. In the APS model, foetuses that showed increased C3 in their brains additionally expressed anxiety-related behaviour after birth. Importantly, USPIO did not affect pregnancy outcomes and liver function in the mother and the offspring, suggesting that this method may be useful for detecting complement activation in vivo in utero and predicting placental insufficiency and abnormal foetal neurodevelopment that leads to neuropsychiatric disorders.