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2.
Am J Clin Nutr ; 111(5): 1048-1058, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32282895

RESUMO

BACKGROUND: Findings from previous studies on associations between prepregnancy dietary patterns and preterm birth and low birth weight (LBW) are limited and inconsistent. OBJECTIVES: To examine the association between prepregnancy dietary patterns and the risk of preterm birth and LBW. METHODS: This study included 3422 and 3508 singleton live births from the Australian Longitudinal Study on Women's Health (ALSWH) for the analyses of preterm birth and LBW, respectively. We included women who were nulliparous and nonpregnant at baseline surveys. We used factor analyses and the Healthy Eating Index-2015 (HEI-2015) score to derive maternal dietary patterns. Four dietary patterns were identified with factor analyses: meats and high-fats; prudent diets; sugar, refined grains, and processed foods; and traditional vegetables. Preterm birth and LBW were assessed using maternal reports from ALSWH data between 2003 and 2015. Multivariable logistic regression analyses were used. RESULTS: Greater adherence to the traditional vegetables pattern before pregnancy was associated with a lower risk of preterm birth and spontaneous preterm birth after adjustments for lifestyle factors and pregnancy complications, highest compared with lowest tertile (adjusted OR = 0.72, 95% CI: 0.53, 0.99) and (RR ratio = 0.62, 95% CI: 0.39, 1.00), respectively. However, these associations were attenuated by the prepregnancy BMI. No significant associations were observed between prepregnancy dietary patterns and LBW. CONCLUSION: This study suggests that better adherence to the traditional vegetables pattern before pregnancy is associated with a lower risk of preterm birth, particularly spontaneous preterm birth among nulliparous women. This finding warrants further examination.


Assuntos
Complicações na Gravidez/prevenção & controle , Nascimento Prematuro/prevenção & controle , Saúde da Mulher , Adulto , Austrália/epidemiologia , Estudos de Coortes , Dieta , Feminino , Humanos , Recém-Nascido de Baixo Peso , Estudos Longitudinais , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/metabolismo , Nascimento Prematuro/epidemiologia , Fatores de Risco , Verduras/metabolismo , Adulto Jovem
3.
Clin Sci (Lond) ; 134(8): 961-984, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32313958

RESUMO

Maternal obesity is associated with pregnancy complications and increases the risk for the infant to develop obesity, diabetes and cardiovascular disease later in life. However, the mechanisms linking the maternal obesogenic environment to adverse short- and long-term outcomes remain poorly understood. As compared with pregnant women with normal BMI, women entering pregnancy obese have more pronounced insulin resistance, higher circulating plasma insulin, leptin, IGF-1, lipids and possibly proinflammatory cytokines and lower plasma adiponectin. Importantly, the changes in maternal levels of nutrients, growth factors and hormones in maternal obesity modulate placental function. For example, high insulin, leptin, IGF-1 and low adiponectin in obese pregnant women activate mTOR signaling in the placenta, promoting protein synthesis, mitochondrial function and nutrient transport. These changes are believed to increase fetal nutrient supply and contribute to fetal overgrowth and/or adiposity in offspring, which increases the risk to develop disease later in life. However, the majority of obese women give birth to normal weight infants and these pregnancies are also associated with activation of inflammatory signaling pathways, oxidative stress, decreased oxidative phosphorylation and lipid accumulation in the placenta. Recent bioinformatics approaches have expanded our understanding of how maternal obesity affects the placenta; however, the link between changes in placental function and adverse outcomes in obese women giving birth to normal sized infants is unclear. Interventions that specifically target placental function, such as activation of placental adiponectin receptors, may prevent the transmission of metabolic disease from obese women to the next generation.


Assuntos
Obesidade Materna/metabolismo , Placenta/metabolismo , Complicações na Gravidez/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Adiposidade , Animais , Feminino , Humanos , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Obesidade Materna/genética , Obesidade Materna/psicologia , Gravidez , Complicações na Gravidez/genética , Complicações na Gravidez/fisiopatologia
4.
Subcell Biochem ; 95: 1-26, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32297294

RESUMO

Vitamin A deficiency studies have been carried out since the early 1900s. Initially, these studies led to the identification of fat soluble A as a unique and essential component of the diet of rodents, birds, and humans. Continuing work established that vitamin A deficiency produces biochemical and physiological dysfunction in almost every vertebrate organ system from conception to death. This chapter begins with a review of representative historical and current studies that used the nutritional vitamin A deficiency research model to gain an understanding of the many roles vitamin A plays in prenatal and postnatal development and well-being. This is followed by a discussion of recent studies that show specific effects of vitamin A deficiency on prenatal development and postnatal maintenance of the olfactory epithelium, brain, and heart. Vitamin A deficiency studies have helped define the necessity of vitamin A for the health of all vertebrates, including farm animals, but the breadth of deficient states and their individual effects on health have not been fully determined. Future work is needed to develop tools to assess the complete vitamin A status of an organism and to define the levels of vitamin A that optimally support molecular and systems level processes during all ages and stages of life.


Assuntos
Desenvolvimento Infantil , Dieta , Deficiência de Vitamina A/metabolismo , Vitamina A/fisiologia , Animais , Dieta/veterinária , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações na Gravidez/metabolismo , Vertebrados/crescimento & desenvolvimento , Vertebrados/metabolismo
5.
Subcell Biochem ; 95: 27-55, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32297295

RESUMO

The placenta, a hallmark of mammalian embryogenesis, allows nutrients to be exchanged between the mother and the fetus. Vitamin A (VA), an essential nutrient, cannot be synthesized by the embryo, and must be acquired from the maternal circulation through the placenta. Our understanding of how this transfer is accomplished is still in its infancy. In this chapter, we recapitulate the early studies about the relationship between maternal dietary/supplemental VA intake and fetal VA levels. We then describe how the discovery of retinol-binding protein (RBP or RBP4), the development of labeling and detection techniques, and the advent of knockout mice shifted this field from a macroscopic to a molecular level. The most recent data indicate that VA and its derivatives (retinoids) and the pro-VA carotenoid, ß-carotene, are transferred across the placenta by distinct proteins, some of which overlap with proteins involved in lipoprotein uptake. The VA status and dietary intake of the mother influence the expression of these proteins, creating feedback signals that control the uptake of retinoids and that may also regulate the uptake of lipids, raising the intriguing possibility of crosstalk between micronutrient and macronutrient metabolism. Many questions remain about the temporal and spatial patterns by which these proteins are expressed and transferred throughout gestation. The answers to these questions are highly relevant to human health, considering that those with either limited or excessive intake of retinoids/carotenoids during pregnancy may be at risk of obtaining improper amounts of VA that ultimately impact the development and health of their offspring.


Assuntos
Desenvolvimento Embrionário , Vitamina A/metabolismo , Animais , Feminino , Humanos , Gravidez , Complicações na Gravidez/metabolismo , Proteínas de Ligação ao Retinol/metabolismo , Deficiência de Vitamina A/metabolismo , beta Caroteno/metabolismo
6.
Mutat Res ; 783: 108295, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32192649

RESUMO

Increasing evidence suggests that early-life events can predispose the newborn to a variety of health issues in later life. In adverse pre- and perinatal conditions, oxidative stress appears to play an important role in the development of future pathological outcomes. From a molecular point of view, oxidative stress can result in genome damage and changes in DNA methylation that can in turn prime pathogenic mechanisms. Interestingly, both alterations have been related to a reciprocal regulation of oxidative stress. The aim of this review is to give a brief overview of the complex relationship linking oxidative stress to DNA damage and methylation and to go through the different sources of exposure that a neonate can encounter in utero or shortly after birth. In this context, the setup of methodologies to monitor the extent of oxidative stress, genomic damage and instability or the presence of altered methylation patterns contributes to the understanding on how the complex events occurring in early life can lead to either a healthy status or a pathological condition.


Assuntos
Dano ao DNA , Metilação de DNA , Estresse Oxidativo , Exposição Ambiental/efeitos adversos , Epigênese Genética , Feminino , Humanos , Recém-Nascido , Doenças Metabólicas/genética , Doenças Metabólicas/metabolismo , Gravidez , Complicações na Gravidez/genética , Complicações na Gravidez/metabolismo , Nascimento Prematuro
7.
Am J Obstet Gynecol ; 223(4): 516-524, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32184147

RESUMO

Iron is essential for the function of all cells through its roles in oxygen delivery, electron transport, and enzymatic activity. Cells with high metabolic rates require more iron and are at greater risk for dysfunction during iron deficiency. Iron requirements during pregnancy increase dramatically, as the mother's blood volume expands and the fetus grows and develops. Thus, pregnancy is a condition of impending or existing iron deficiency, which may be difficult to diagnose because of limitations to commonly used biomarkers such as hemoglobin and ferritin concentrations. Iron deficiency is associated with adverse pregnancy outcomes, including increased maternal illness, low birthweight, prematurity, and intrauterine growth restriction. The rapidly developing fetal brain is at particular risk of iron deficiency, which can occur because of maternal iron deficiency, hypertension, smoking, or glucose intolerance. Low maternal gestational iron intake is associated with autism, schizophrenia, and abnormal brain structure in the offspring. Newborns with iron deficiency have compromised recognition memory, slower speed of processing, and poorer bonding that persist despite postnatal iron repletion. Preclinical models of fetal iron deficiency confirm that expected iron-dependent processes such as monoamine neurotransmission, neuronal growth and differentiation, myelination, and gene expression are all compromised acutely and long term into adulthood. This review outlines strategies to diagnose and prevent iron deficiency in pregnancy. It describes the neurocognitive and mental health consequences of fetal iron deficiency. It emphasizes that fetal iron is a key nutrient that influences brain development and function across the lifespan.


Assuntos
Desenvolvimento Fetal/fisiologia , Distúrbios do Metabolismo do Ferro/tratamento farmacológico , Ferro/deficiência , Complicações na Gravidez/tratamento farmacológico , Oligoelementos/uso terapêutico , Encéfalo/embriologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Feminino , Humanos , Ferro/metabolismo , Ferro/fisiologia , Ferro/uso terapêutico , Distúrbios do Metabolismo do Ferro/epidemiologia , Distúrbios do Metabolismo do Ferro/metabolismo , Distúrbios do Metabolismo do Ferro/fisiopatologia , Transtornos Mentais/epidemiologia , Transtornos do Neurodesenvolvimento/epidemiologia , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/metabolismo , Complicações na Gravidez/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia
8.
Psychopharmacology (Berl) ; 237(4): 915-941, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32065252

RESUMO

Perinatal depression is the most common complication of pregnancy and affects the mother, fetus, and infant. Recent preclinical studies and a limited number of clinical studies have suggested an influence of the gut microbiome on the onset and course of mental health disorders. In this review, we examine the current state of knowledge regarding genetics, epigenetics, heritability, and neuro-immuno-endocrine systems biology in perinatal mood disorders, with a particular focus on the interaction between these factors and the gut microbiome, which is mediated via the gut-brain axis. We also provide an overview of experimental and analytical methods that are currently available to researchers interested in elucidating the influence of the gut microbiome on mental health disorders during pregnancy and postpartum.


Assuntos
Transtorno Depressivo Maior/terapia , Microbioma Gastrointestinal/fisiologia , Medicina de Precisão/métodos , Complicações na Gravidez/terapia , Encéfalo/metabolismo , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Lactente , Microbiota/fisiologia , Período Pós-Parto/metabolismo , Período Pós-Parto/psicologia , Medicina de Precisão/psicologia , Gravidez , Complicações na Gravidez/metabolismo , Complicações na Gravidez/psicologia
9.
J Steroid Biochem Mol Biol ; 199: 105611, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32007562

RESUMO

Gestational hypercalcemia is associated with an increased risk of maternal, fetal and neonatal morbidity and mortality. Hypercalcemia may develop during pregnancy in individuals who were previously asymptomatic. The increased sensitivity during pregnancy may be related to physiological, gestational alterations in vitamin D and calcium metabolism and may be influenced by gene variants. The prevalence is unknown. We investigated the prevalence of hypercalcemia in trimester 3 (T3) in a population representative prospective cohort study (n = 1832) in South-West Sweden. Women with serum albumin (Alb) adjusted calcium (CaAlb) ≥ 2.65 mmol/L in T3 (n = 30) were matched to normo-calcemic controls, and markers of calcium and vitamin D metabolism were investigated in trimester 1 (T1) and T3. Serum concentrations of Ca, phosphate (P), Magnesium (Mg), Alb and creatinine (Cr), parathyroid hormone (PTH; T3 only), vitamin D metabolites (total 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, and free 25(OH)D) were analysed in T1 and T3. CaAlb (Payne; inter-laboratory difference: UEA = 0.15 + 0.9*UGOT; UEA 2.54 = UGOT 2.65) and estimated glomerular filtration rate (eGFR; modified 4-variable MDRD) and vitamin D metabolites ratios (VMR) were calculated. Normally and non-normally distributed data were presented as mean (SD) or median (95 %CI). Group differences in relationships between vitamin D metabolites and with PTH were investigated with multiple regression analyses. Hypercalcemia in T3 was found in 1.7 % of women. PTH concentrations suggestive of primary hyperparathyroidism was found in 1 woman and none had 25(OH)D or 24,25(OH)2D concentrations in the toxicity range or suggestive of mutations in the CYP24A1 gene. CaAlb was significantly higher in hypercalcemic cases compared to controls in T1 (2.44 (2.30-2.80) vs 2.37 (2.25-2.49) mmol/L) and T3 (2.63 (2.52-2.78) vs 2.46 (2.31-2.58) mmol/L). Serum P was higher among cases than controls in T3 (1.12 (0.16) vs 1.07 (0.18) mmol/L) but not in T1 (1.12 (0.18) and 1.12 (0.16) mmol/L). PTH in T3 was lower in cases (1.6 (1.6-2.8) vs 2.3 (2.1-2.8) pmol/L) but 1,25(OH)2D concentrations were similar. There were no significant group differences in serum 25(OH)D, free 25(OH)D, 24,25(OH)2D, Mg, Alb, Cr and eGFR. Regression analyses did not show significant differences between cases and controls in relationships between vitamin D metabolites and with PTH, except for the free 25(OH)D-PTH relationship and a higher free:total 25(OH)D ratio in cases at T1. In conclusion, most common causes of hypercalcemia were excluded in the majority of women. Hypercalcemic women had a relatively high serum 1,25(OH)2D concentration despite an appropriately suppressed PTH, suggestive of abnormal gestational adaptions.


Assuntos
Cálcio/sangue , Hipercalcemia/metabolismo , Complicações na Gravidez/metabolismo , Vitamina D/metabolismo , Adulto , Cálcio/metabolismo , Cálcio na Dieta/uso terapêutico , Creatinina/sangue , Feminino , Humanos , Hipercalcemia/sangue , Hipercalcemia/epidemiologia , Magnésio/sangue , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/metabolismo , Fosfatos/sangue , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/epidemiologia , Albumina Sérica/metabolismo , Suécia/epidemiologia , Vitamina D/sangue
10.
Sci Rep ; 10(1): 3660, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32107447

RESUMO

Gestational Diabetes Mellitus (GDM), which is correlated with changes in the gut microbiota, is a risk factor for neonatal inborn errors of metabolism (IEMs). Maternal hyperglycemia exerts epigenetic effects on genes that encode IEM-associated enzymes, resulting in changes in the neonatal blood metabolome. However, the relationship between maternal gut microbiota and the neonatal blood metabolome remains poorly understood. This study aimed at understanding the connections between maternal gut microbiota and the neonatal blood metabolome in GDM. 1H-NMR-based untargeted metabolomics was performed on maternal fecal samples and targeted metabolomics on the matched neonatal dry blood spots from a cohort of 40 pregnant women, including 22 with GDM and 18 controls. Multi-omic association methods (including Co-Inertia Analysis and Procrustes Analysis) were applied to investigate the relationship between maternal fecal metabolome and the neonatal blood metabolome. Both maternal fecal metabolome and the matched neonatal blood metabolome could be separated along the vector of maternal hyperglycemia. A close relationship between the maternal and neonatal metabolomes was observed by multi-omic association approaches. Twelve out of thirty-two maternal fecal metabolites with altered abundances from 872 1H- NMR features (Bonferroni-adjusted P < 0.05) in women with GDM and the controls were identified, among which 8 metabolites contribute (P < 0.05 in a 999-step permutation test) to the close connection between maternal and the neonatal metabolomes in GDM. Four of these eight maternal fecal metabolites, including lysine, putrescine, guanidinoacetate, and hexadecanedioate, were negatively associated (Spearman rank correlation, coefficient value < -0.6, P < 0.05) with maternal hyperglycemia. Biotin metabolism was enriched (Bonferroni-adjusted P < 0.05 in the hypergeometric test) with the four-hyperglycemia associated fecal metabolites. The results of this study suggested that maternal fecal metabolites contribute to the connections between maternal fecal metabolome and the neonatal blood metabolome and may further affect the risk of IEMs.


Assuntos
Diabetes Insípido/metabolismo , Fezes , Metaboloma , Complicações na Gravidez/metabolismo , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez
11.
BMJ Case Rep ; 13(2)2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32041755

RESUMO

In Ecuador, a developing South American country, subjects affected with genetic syndromes of severe short stature are commonly referred to as dwarfs or midgets. Furthermore, and because in earlier studies some patients had evidenced mental retardation, such abnormality is assumed to exist in all affected subjects. Herein, we present two discrete instances in which this type of branding occurs. The first is that of individuals with Laron syndrome who are still called 'dwarfs' and considered as having a degree of mental retardation despite evidence showing otherwise. A similar problem, that of a girl affected with a genetic syndrome of short stature, which might include mental retardation, is also discussed. Considering that stigmatising is a form of discrimination, it concerns us all. Hence, the use of derogatory terms such as midget, dwarf or cretin, that might unintentionally occur even when delivering the best and most devoted medical care, must be eliminated.


Assuntos
Síndrome de Cornélia de Lange/genética , Síndrome de Cornélia de Lange/psicologia , Síndrome de Laron/psicologia , Estereotipagem , Atitude do Pessoal de Saúde , Pré-Escolar , Síndrome de Cornélia de Lange/tratamento farmacológico , Países em Desenvolvimento , Equador , Feminino , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações na Gravidez/metabolismo , Proteínas Repressoras/genética , Terminologia como Assunto
12.
Nitric Oxide ; 96: 1-12, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31911124

RESUMO

The three known gasotransmitters, nitric oxide, carbon monoxide, and hydrogen sulfide are involved in key processes throughout pregnancy. Gasotransmitters are known to impact on smooth muscle tone, regulation of immune responses, and oxidative state of cells and their component molecules. Failure of the systems that tightly regulate gasotransmitter production and downstream effects are thought to contribute to common maternal diseases such as preeclampsia and preterm birth. Normal pregnancy-related changes in uterine blood flow depend heavily on gasotransmitter signaling. In preeclampsia, endothelial dysfunction is a major contributor to aberrant gasotransmitter signaling, resulting in hypertension after 20 weeks gestation. Maintenance of pregnancy to term also requires gasotransmitter-mediated uterine quiescence. As the appropriate signals for parturition occur, regulation of gasotransmitter signaling must work in concert with those endocrine signals in order for appropriate labor and delivery timing. Like preeclampsia, preterm birth may have origins in abnormal gasotransmitter signaling. We review the evidence for the involvement of gasotransmitters in preeclampsia and preterm birth, as well as mechanistic and molecular signaling targets.


Assuntos
Monóxido de Carbono/metabolismo , Gasotransmissores/metabolismo , Sulfeto de Hidrogênio/metabolismo , Óxido Nítrico/metabolismo , Complicações na Gravidez/tratamento farmacológico , Animais , Monóxido de Carbono/fisiologia , Monóxido de Carbono/uso terapêutico , Feminino , Gasotransmissores/fisiologia , Gasotransmissores/uso terapêutico , Humanos , Sulfeto de Hidrogênio/uso terapêutico , Óxido Nítrico/fisiologia , Parto/efeitos dos fármacos , Parto/fisiologia , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/fisiopatologia , Gravidez , Complicações na Gravidez/metabolismo , Complicações na Gravidez/fisiopatologia , Nascimento Prematuro/metabolismo , Nascimento Prematuro/fisiopatologia
13.
Metabolism ; 104: 154142, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31930973

RESUMO

CONTEXT: Maternal obesity is a significant public health concern that contributes to unfavorable outcomes such as inflammation and insulin resistance. Women with obesity may have impaired metabolic flexibility (i.e. an inability to adjust substrate metabolism according to fuel availability). Impaired metabolic flexibility during pregnancy may mediate poor pregnancy outcomes in women with obesity. PURPOSE: The purposes of this study were to: 1) compare metabolic flexibility between overweight/obese and lean women; and 2) determine the relationships between metabolic flexibility, inflammation following a high-fat meal, and maternal metabolic health outcomes (i.e. gestational weight gain and insulin resistance). PROCEDURES: This interventional physiology study assessed lipid oxidation rates via indirect calorimetry before and after consumption of a high-fat meal. The percent change in lipid metabolism was calculated to determine 'metabolic flexibility.' Maternal inflammatory profiles (CRP, IL-6, IL-8, IL-10, IL-12, TNF-α) and insulin resistance (HOMA-IR) were determined via plasma analyses. MAIN FINDINGS: 64 women who were pregnant (lean = 35, overweight/obese = 29) participated between 32 and 38 weeks gestation. Lean women had significantly higher metabolic flexibility compared to overweight/obese women (lean 48.0 ±â€¯34.1% vs overweight/obese 29.3 ±â€¯34.3%, p = .035). Even when controlling for pre-pregnancy BMI, there was a negative relationship between metabolic flexibility and percent change in CRP among the overweight/obese group (r = -0.526, p = .017). Metabolic flexibility (per kg fat free mass) was negatively correlated with postprandial HOMA-IR (2 h: r = -0.325, p = .016; 4 h: r = -0.319, p = .019). CONCLUSIONS: Overweight and obese women who are pregnant are less 'metabolically flexible' than lean women, and this is related to postprandial inflammation and insulin resistance.


Assuntos
Inflamação/metabolismo , Resistência à Insulina , Obesidade/metabolismo , Sobrepeso/metabolismo , Complicações na Gravidez/metabolismo , Adolescente , Adulto , Índice de Massa Corporal , Citocinas/sangue , Dieta Hiperlipídica , Feminino , Humanos , Metabolismo dos Lipídeos , Refeições , Gravidez , Ganho de Peso , Adulto Jovem
14.
Int J Mol Sci ; 21(2)2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31940810

RESUMO

In the first trimester of pregnancy, placental development involves a wide range of cellular processes. These include trophoblast proliferation, fusion, and differentiation, which are dependent on tight cell cycle control. The intrauterine environment affects placental development, which also includes the trophoblast cell cycle. In this work, we focus on maternal obesity to assess whether an altered intrauterine milieu modulates expression and protein levels of placental cell cycle regulators in early human pregnancy. For this purpose, we use first trimester placental tissue from lean and obese women (gestational week 5+0-11+6, n = 58). Using a PCR panel, a cell cycle protein array, and STRING database analysis, we identify a network of cell cycle regulators increased by maternal obesity in which breast cancer 1 (BRCA1) is a central player. Immunostaining localizes BRCA1 predominantly to the villous and the extravillous cytotrophoblast. Obesity-driven BRCA1 upregulation is not able to be explained by DNA methylation (EPIC array) or by short-term treatment of chorionic villous explants at 2.5% oxygen with tumor necrosis factor α (TNF-α) (50 mg/mL), leptin (100 mg/mL), interleukin 6 (IL-6) (100 mg/mL), or high glucose (25 nM). Oxygen tension rises during the first trimester, but this change in vitro has no effect on BRCA1 (2.5% and 6.5% O2). We conclude that maternal obesity affects placental cell cycle regulation and speculate this may alter placental development.


Assuntos
Proteína BRCA1/metabolismo , Proteínas de Ciclo Celular/metabolismo , Obesidade/metabolismo , Complicações na Gravidez/metabolismo , Adulto , Proteína BRCA1/genética , Proteínas de Ciclo Celular/genética , Feminino , Glucose/metabolismo , Humanos , Interleucina-6/metabolismo , Leptina/genética , Leptina/metabolismo , Obesidade/genética , Oxigênio/metabolismo , Gravidez , Primeiro Trimestre da Gravidez/metabolismo , Trofoblastos/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
15.
BMC Pregnancy Childbirth ; 19(1): 479, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805950

RESUMO

BACKGROUND: Antenatal depression affects 10-20% of pregnant women. Around 2-4% of European pregnant women use antidepressant treatment, most commonly selective serotonin reuptake inhibitors (SSRIs). Poor pregnancy outcomes, such as preterm birth and low birth weight, have been described in women with antenatal depression and in pregnant women on SSRI treatment. However, the effects of antenatal depression and antidepressant treatment on the placenta are largely unknown. The aim of this work was to compare placental gene and protein expression in healthy women, women with untreated antenatal depression and women on antidepressant treatment during pregnancy. METHODS: Placental samples from 47 controls, 25 depressed and 45 SSRI-treated women were analysed by means of qPCR using custom-designed TaqMan low-density arrays (TLDAs) for 44 genes previously known to be involved in the pathophysiology of depression, and expressed in the placenta. Moreover, placental protein expression was determined by means of immunohistochemistry in 37 healthy controls, 13 women with untreated depression and 21 women on antidepressant treatment. Statistical comparisons between groups were performed by one-way ANOVA or the Kruskal-Wallis test. RESULTS: Nominally significant findings were noted for HTR1A and NPY2R, where women with untreated depression displayed higher gene expression than healthy controls (p < 0.05), whereas women on antidepressant treatment had similar expression as healthy controls. The protein expression analyses revealed higher expression of HTR1A in placentas from women on antidepressant treatment, than in placentas from healthy controls (p < 0.05). CONCLUSION: The differentially expressed HTR1A, both at the gene and the protein level that was revealed in this study, suggests the involvement of HTR1A in the effect of antenatal depression on biological mechanisms in the placenta. More research is needed to elucidate the role of depression and antidepressant treatment on the placenta, and, further, the effect on the fetus.


Assuntos
Antidepressivos/efeitos adversos , Depressão/tratamento farmacológico , Placenta/metabolismo , Complicações na Gravidez/tratamento farmacológico , Proteínas da Gravidez/metabolismo , Adulto , Antidepressivos/uso terapêutico , Depressão/genética , Depressão/metabolismo , Feminino , Expressão Gênica , Voluntários Saudáveis , Humanos , Imuno-Histoquímica , Placenta/patologia , Gravidez , Complicações na Gravidez/genética , Complicações na Gravidez/metabolismo , Proteínas da Gravidez/genética , Efeitos Tardios da Exposição Pré-Natal , Reação em Cadeia da Polimerase em Tempo Real , Receptor 5-HT1A de Serotonina/metabolismo , Inibidores de Captação de Serotonina/efeitos adversos , Inibidores de Captação de Serotonina/uso terapêutico
16.
Biomed Res Int ; 2019: 3261279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781611

RESUMO

Aim: To determine whether the area of the foveal avascular zone (FAZ), as a morphological indicator of the microcirculation of the perifoveal capillary network, changes in the carbohydrate metabolism disorders during pregnancy (the gestational age of patients with gestational diabetes mellitus (GDM) and preexisting diabetes (PexD)). Methods: Ten normal individuals and 41 eyes of 41 patients, 28 with GDM and 13 with PexD, were studied. A 3 × 3 mm area of the FAZ of the superficial capillary plexus layer (SCP) and the deep capillary plexus layer (DCP) was determined by optical coherence tomography angiography (OCTA; RS-3000 Advance, NIDEK). The significance of the correlation between the size of the FAZ and the weeks of pregnancy was determined. Results: The area of the FAZ of the SCP was 0.38 ± 0.11 mm2 (normal eyes), 0.41 ± 0.16 mm2 (GDM), and 0.43 ± 0.10 mm2 (PexD). The area of the FAZ of the DCP was 0.78 ± 0.23 mm2 (normal eyes), 0.69 ± 0.16 mm2 (GDM), and 0.79 ± 0.25 mm2 (PexD). No significant difference in the FAZ sizes was observed between the groups. The average number of weeks of pregnancy was 24.1 ± 8.2 weeks in the eyes with GDM and 23.3 ± 11.4 weeks in the eyes with PexD (P > 0.05). Significant correlations were found between the size of the FAZ of the SCP and the number of weeks (r = 0.37, P=0.04 for GDM, and r = 0.49, P=0.04 for PexD, Spearman's rank-order correlation coefficient). Conclusions: For GDM and PexD under established glycemic control, the area of the FAZ is not affected, but vascular changes occurred at the early phase of pregnancy.


Assuntos
Erros Inatos do Metabolismo dos Carboidratos/metabolismo , Fóvea Central/metabolismo , Macula Lutea/metabolismo , Complicações na Gravidez/metabolismo , Adulto , Metabolismo dos Carboidratos/genética , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico por imagem , Erros Inatos do Metabolismo dos Carboidratos/patologia , Diabetes Mellitus/diagnóstico por imagem , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Diabetes Gestacional/diagnóstico por imagem , Diabetes Gestacional/metabolismo , Diabetes Gestacional/patologia , Feminino , Fóvea Central/irrigação sanguínea , Fóvea Central/diagnóstico por imagem , Fóvea Central/patologia , Humanos , Macula Lutea/irrigação sanguínea , Macula Lutea/diagnóstico por imagem , Macula Lutea/patologia , Masculino , Gravidez , Complicações na Gravidez/patologia , Tomografia de Coerência Óptica
17.
J Neuroinflammation ; 16(1): 226, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31733653

RESUMO

BACKGROUND: Chemerin is highly expressed in the serum, placenta tissue, and umbilical cord blood of diabetic mother; however, the impact of chemerin on cognitive disorders of offspring from mothers with diabetes in pregnancy remains unclear. METHODS: A diabetic phenotype in pregnant mice dams was induced by streptozocin (STZ) injection or intraperitoneal injection of chemerin. Behavioral changes in offspring of diabetic dams and nondiabetic controls were assessed, and changes in chemerin, two receptors of chemerin [chemerin receptor 23 (ChemR23) and chemokine (C-C motif) receptor-like 2 (CCRL2)], macrophages, and neurons in the brain tissue were studied to reveal the underlying mechanism of the behavioral changes. RESULTS: Chemerin treatment mimicked the STZ-induced symptom of maternal diabetes in mice along with the altered behavior of offspring in the open field test (OFT) assay. In the exploring process for potential mechanism, the brain tissues of offspring from chemerin-treated dams were observed with an increase level of macrophage infiltration and a decrease number of neuron cells. Moreover, an increased level of NOD-like receptor family pyrin domain containing 3 (NLRP3) and apoptosis-associated speck-like (Asc) protein as well as pyroptosis [characterized by increased active caspase-1 content and secretion of cytokines such as interleukin (IL) 1 beta (IL-1ß) and IL-18] more activated in macrophages is also observed in the brain of these diabetic dam's offspring, in the presence of ChemR23. In vitro, it was found that pyroptosis activation was increased in macrophages separated from the abdominal cavity of normal mice, after chemerin treatment. However, depletion of CCRL2 decreased the level of chemerin in the brain tissues of diabetic dams' offspring; depletion of ChemR23 decreased macrophage pyroptosis, and depletion of either receptor reversed chemerin-mediated neurodevelopmental deficits and cognitive impairment of offspring of diabetic pregnant dams. CONCLUSIONS: Chemerin induced diabetic pregnant disease and CCRL2 were required to enrich chemerin in the brain of offspring. Aggregation of chemerin could lead to macrophage recruitment, activation of pyroptosis, the release of inflammatory cytokines, a decrease in the number of neurons, and cognitive impairment in offspring in a ChemR23-dependent manner. Targeting CCRL2 and/or ChemR23 could be useful for treating neuropsychological deficits in offspring of dams with diabetes in pregnancy.


Assuntos
Encéfalo/patologia , Quimiocinas/farmacologia , Transtornos Cognitivos/etiologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Macrófagos/patologia , Efeitos Tardios da Exposição Pré-Natal , Animais , Encéfalo/metabolismo , Quimiocinas/metabolismo , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Diabetes Mellitus Experimental , Feminino , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Camundongos , Gravidez , Complicações na Gravidez/etiologia , Complicações na Gravidez/metabolismo , Complicações na Gravidez/patologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia , Piroptose/fisiologia , Receptores CCR/metabolismo
18.
Adv Neonatal Care ; 19(6): E11-E20, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31764138

RESUMO

BACKGROUND: Several factors can influence the production of mothers' own milk. PURPOSE: To assess the influence of maternal psychological stress, maternal cortisol levels, and neonatal hair cortisol levels on timing of secretory activation. METHODS: A prospective study was conducted at 2 public health centers in Andalusia, Spain. Participants were 60 pregnant women and their 60 neonates. Hair cortisol levels and psychological stress (pregnancy-specific stress [Prenatal Distress Questionnaire, PDQ] and perceived stress [Perceived Stress Scale, PSS]) were evaluated during the third trimester and the postpartum period. This study was part of the GESTASTRESS cohort study on the effects of stress during pregnancy. RESULTS: Higher PDQ and PSS scores (P < .05) in the third trimester were associated with later onset of secretory activation. Higher postpartum maternal hair cortisol levels were associated with a delayed secretory activation of mother's own milk (P < .05). IMPLICATIONS FOR RESEARCH: Future studies should look at the influence of psychological stress and cortisol levels on hormones involved in mother's own milk production. IMPLICATIONS FOR PRACTICE: Neonatal nurses and other healthcare providers should be familiar with levels of neonates' exposure to maternal prenatal stress prior to birth.


Assuntos
Análise do Cabelo/métodos , Hidrocortisona/análise , Lactação , Complicações na Gravidez , Estresse Psicológico/metabolismo , Adulto , Aleitamento Materno/psicologia , Correlação de Dados , Feminino , Humanos , Recém-Nascido , Lactação/metabolismo , Lactação/psicologia , Leite Humano/metabolismo , Período Pós-Parto/metabolismo , Período Pós-Parto/psicologia , Gravidez , Complicações na Gravidez/metabolismo , Complicações na Gravidez/psicologia , Terceiro Trimestre da Gravidez/metabolismo , Terceiro Trimestre da Gravidez/psicologia , Espanha
19.
Arch Biochem Biophys ; 676: 108125, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31586554

RESUMO

Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder occurred in pregnant women, and the mechanism for such disease is still unclear. The bioinformatics analysis of our previous study has revealed the abnormal expression of endoplasmic reticulum protein 29 (ERp29) in placental tissue of ICP patients. In this study, the function of ERp29 was further explored using in vitro model of ICP. The results showed that up-regulation of ERp29 occurred in TCA (taurocholic acid)-treated human trophoblast HTR-8/SVeno cells, and ERp29 inhibition reversed TCA toxicity via attenuating G2/M arrest and cell apoptosis. Mechanical study revealed ERp29 inhibition suppressed phosphorylation and kinase activity of p38, thus subsequently affecting expression and phosphorylation of p53 (ser18) as well as the transcriptional activity of p53. The conduction of this study might confirm the important role of ERp29 in ICP and which would be helpful for the development of target therapeutic method for ICP.


Assuntos
Técnicas de Silenciamento de Genes , Proteínas de Choque Térmico/genética , Ácido Taurocólico/toxicidade , Trofoblastos/citologia , Trofoblastos/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular , Colestase Intra-Hepática/genética , Colestase Intra-Hepática/metabolismo , Colestase Intra-Hepática/patologia , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Proteínas de Choque Térmico/deficiência , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase M do Ciclo Celular/genética , Fosforilação/efeitos dos fármacos , Fosforilação/genética , Gravidez , Complicações na Gravidez/genética , Complicações na Gravidez/metabolismo , Complicações na Gravidez/patologia , Trofoblastos/efeitos dos fármacos
20.
Nutrients ; 11(9)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505767

RESUMO

This study analyzed how maternal obesity affected fatty acids (FAs) in breast milk and their association with infant growth and cognition to raise awareness about the programming effect of maternal health and to promote a healthy prenatal weight. Mother-child pairs (n = 78) were grouped per maternal pre-pregnancy body mass index (BMI): normal-weight (BMI = 18.5-24.99), overweight (BMI = 25-29.99) and obese (BMI > 30). Colostrum and mature milk FAs were determined. Infant anthropometry at 6, 18 and 36 months of age and cognition at 18 were analyzed. Mature milk exhibited lower arachidonic acid (AA) and docosahexaenoic acid (DHA), among others, than colostrum. Breast milk of non-normal weight mothers presented increased saturated FAs and n6:n3 ratio and decreased α-linolenic acid (ALA), DHA and monounsaturated FAs. Infant BMI-for-age at 6 months of age was inversely associated with colostrum n6 (e.g., AA) and n3 (e.g., DHA) FAs and positively associated with n6:n3 ratio. Depending on the maternal weight, infant cognition was positively influenced by breast milk linoleic acid, n6 PUFAs, ALA, DHA and n3 LC-PUFAs, and negatively affected by n6:n3 ratio. In conclusion, this study shows that maternal pre-pregnancy BMI can influence breast milk FAs and infant growth and cognition, endorsing the importance of a healthy weight in future generations.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Cognição/efeitos dos fármacos , Ácidos Graxos/análise , Leite Humano/química , Obesidade/metabolismo , Índice de Massa Corporal , Pré-Escolar , Colostro/química , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Complicações na Gravidez/metabolismo , Efeitos Tardios da Exposição Pré-Natal/etiologia
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