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1.
Clin Nutr ; 40(5): 3650-3660, 2021 05.
Article in English | MEDLINE | ID: mdl-33423808

ABSTRACT

BACKGROUND & AIMS: This study aims to explore the associations of vitamin D (VD) metabolic pathway gene with 25(OH)D level in pregnant women and the interactions of SNP with season and VD supplement. METHODS: A total of 2658 pregnant women were selected from Zhoushan Pregnant Women Cohort study. Gestational 25(OH)D level and single nucleotide polymorphism (SNP) of VD metabolic pathway gene were detected. Multilinear regression models were used to estimate associations of SNPs with gestational 25(OH)D levels. Stratified analyses were performed to test the interactions of SNP with season and VD supplements. RESULTS: The mutations of rs2298849 and rs7041 on the GC gene were respectively associated with higher 25(OH)D in the first and third trimester; the mutations of seven SNPs (rs1155563, rs16846876, rs17467825, rs2282679, rs2298850, rs3755967, and rs4588) on the GC gene were respectively associated with lower 25(OH)D both in the first and third trimester, and lower changes in 25(OH)D during late pregnancy. The mutations of above seven SNPs, except for rs1155563, were also respectively associated with lower 25(OH)D in the second trimester, but to a lesser extent; Besides, pregnant women with mutation on CYP24A1-rs2209314 had a higher increment in 25(OH)D than their counterparts in the second trimester. The increasing dose effect of Gc isoform on 25(OH)D was observed. The associations of GC and LRP2 genes with 25(OH)D modified by season and VD supplements. CONCLUSIONS: The polymorphisms of VD metabolic pathway gene were associated with gestational 25(OH)D, and the associations differ by seasons and VD supplements. Gc isoform exerted a profound influence on gestational 25(OH)D.


Subject(s)
Dietary Supplements , Pregnancy , Vitamin D-Binding Protein/genetics , Vitamin D , Adult , China , Cohort Studies , Female , Humans , Polymorphism, Single Nucleotide/genetics , Pregnancy/blood , Pregnancy/genetics , Pregnancy/statistics & numerical data , Pregnancy Complications/epidemiology , Pregnancy Complications/genetics , Seasons , Vitamin D/blood , Vitamin D/genetics , Vitamin D/metabolism , Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/genetics
2.
Mol Metab ; 36: 100963, 2020 06.
Article in English | MEDLINE | ID: mdl-32283518

ABSTRACT

OBJECTIVE: Maternal unbalanced nutritional habits during embryonic development and perinatal stages perturb hypothalamic neuronal programming of the offspring, thus increasing obesity-associated diabetes risk. However, the underlying molecular mechanisms remain largely unknown. In this study we sought to determine the translatomic signatures associated with pro-opiomelanocortin (POMC) neuron malprogramming in maternal obesogenic conditions. METHODS: We used the RiboTag mouse model to specifically profile the translatome of POMC neurons during neonatal (P0) and perinatal (P21) life and its neuroanatomical, functional, and physiological consequences. RESULTS: Maternal high-fat diet (HFD) exposure did not interfere with offspring's hypothalamic POMC neuron specification, but significantly impaired their spatial distribution and axonal extension to target areas. Importantly, we established POMC neuron-specific translatome signatures accounting for aberrant neuronal development and axonal growth. These anatomical and molecular alterations caused metabolic dysfunction in early life and adulthood. CONCLUSIONS: Our study provides fundamental insights on the molecular mechanisms underlying POMC neuron malprogramming in obesogenic contexts.


Subject(s)
Obesity/genetics , Prenatal Exposure Delayed Effects/metabolism , Pro-Opiomelanocortin/metabolism , Animals , DNA/genetics , DNA Methylation , Diet, High-Fat , Female , Genome-Wide Association Study , Hypothalamus/metabolism , Male , Mice , Neurogenesis/genetics , Neurons/metabolism , Obesity/metabolism , Pregnancy/genetics , Pregnancy/metabolism , Pro-Opiomelanocortin/physiology
3.
Am J Clin Nutr ; 111(3): 555-561, 2020 03 01.
Article in English | MEDLINE | ID: mdl-31942922

ABSTRACT

BACKGROUND: Epigenetic aging is associated with higher risk of cardiovascular disease, cancer, and all-cause mortality and may be a mechanistic link between early-life exposures, such as maternal dietary characteristics during pregnancy, and risk of adult disease. OBJECTIVES: We sought to determine the early-life risk factors for newborn epigenetic aging, specifically maternal dietary macronutrient intake, and whether epigenetic aging is associated with cardiovascular health markers in the newborn. METHODS: Epigenetic age acceleration of 169 newborns was measured from saliva using the Horvath age calculator. Maternal diet during pregnancy was assessed using food-frequency questionnaires. RESULTS: Newborns with positive age acceleration were more likely to be female and have greater body fatness. Maternal intakes of saturated fat [6.2 wk epigenetic age acceleration (95% CI: 1.0, 11.3) per 5% of energy; P = 0.02] and monounsaturated fat [12.4 wk (95% CI: 4.2, 20.5) per 5% of energy; P = 0.003] were associated with higher epigenetic age acceleration in the newborn. The strongest association of individual fatty acids were for palmitoleic acid (25.3 wk; 95% CI: 11.4, 39.2; P = 0.0004), oleic acid (2.2 wk; 95% CI: 0.8, 3.6; P = 0.002), and palmitic acid (2.9 wk; 95% CI: 1.0, 4.9; P = 0.004) per 1% of energy intake. Vitamin D supplementation was associated with lower epigenetic age acceleration (-8.1 wk; 95% CI: -14.5, -1.7; P = 0.01). Epigenetic age acceleration was associated with aortic intima-media thickness in preterm infants [1.0 µm (95% CI: 0.2, 1.8) per week of epigenetic age acceleration; P = 0.01], but not among those born at term (P = 0.78). Epigenetic age acceleration was not associated with heart rate variability in either preterm or term born infants (both P > 0.2). CONCLUSIONS: This study provides evidence of maternal dietary characteristics that are associated with epigenetic aging in the offspring. Prospective intervention studies are required to determine whether such associations are causal.


Subject(s)
DNA Methylation , Epigenesis, Genetic , Maternal Nutritional Physiological Phenomena , Pregnancy/metabolism , Adult , Carotid Intima-Media Thickness , Energy Intake , Epigenomics , Female , Humans , Infant , Infant, Newborn , Male , Pregnancy/genetics , Prospective Studies
4.
Reprod Domest Anim ; 55(1): 21-28, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31626709

ABSTRACT

The aim of this study was to analyse changes in the abundance of prolactin (PRL) receptor (PRLR) and suppressor of cytokine signalling-3 (SOCS-3) mRNA in the ventro-/dorsomedial nucleus (VMH/DMH) and arcuate nucleus (ARC) of the hypothalamus as well as in the median eminence (ME) and adenohypophysis (AP) in sheep at 30, 60, 90 and 120 d of pregnancy compared to non-pregnant animals. In the VMH/DMH, PRLR transcripts were detected only in non-pregnant ewes. In the ARC, the abundances of PRLR mRNA were higher in pregnant sheep on days 30 (p < .01), 90 (p < .01) and 120 (p < .05) than in non-pregnant sheep. In contrast, the expression of PRLR mRNA in the ME was lower (p < .01) in pregnant ewes at days 30 and 60 than in non-pregnant ewes and was undetectable at later stages of gestation. In all studied stages of pregnancy except day 60, the abundance of PRLR mRNA was higher (p < .01) in the ARC than in the AP, while in non-pregnant sheep, there were no differences (p ≥ .05) in the transcript levels between these two tissues. In non-pregnant ewes, the abundance of SOCS-3 mRNA in the AP was lower than that in any other studied tissue (p < .05-p < .01). In conclusion, the observed changes in PRLR and SOCS-3 mRNA abundance in the hypothalamus and AP during pregnancy may be important components of the mechanisms regulating the action of PRL in energy homeostasis and neuroendocrine interactions within the hypothalamic-pituitary axis.


Subject(s)
Hypothalamus/metabolism , Pituitary Gland, Anterior/metabolism , Pregnancy/metabolism , Receptors, Prolactin/metabolism , Suppressor of Cytokine Signaling Proteins/metabolism , Animals , Female , Gene Expression Profiling , Pregnancy/genetics , RNA, Messenger/metabolism , Receptors, Prolactin/genetics , Sheep, Domestic/genetics , Sheep, Domestic/metabolism , Suppressor of Cytokine Signaling Proteins/genetics
5.
Am J Clin Nutr ; 110(6): 1370-1383, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31589250

ABSTRACT

BACKGROUND: Fatty acids are a vital component of human milk. They influence infant neurodevelopment and immune function, and they provide ∼50% of milk's energy content. OBJECTIVES: The objectives of this study were to characterize the composition of human milk fatty acids in a large Canadian birth cohort and identify factors influencing their variability. METHODS: In a subset of the CHILD cohort (n = 1094), we analyzed milk fatty acids at 3-4 mo postpartum using GLC. Individual and total SFAs, MUFAs, and n-3 and n-6 PUFAs were analyzed using SD scores and principal component analysis (PCA). Maternal diet, sociodemographic, health, and environmental factors were self-reported. Single-nucleotide polymorphisms were assessed in the fatty acid desaturase 1 (FADS1-rs174556) and 2 (FADS2-rs174575) genes. RESULTS: Fatty acid profiles were variable, with individual fatty acid proportions varying from 2- to >30-fold between women. Using PCA, we identified 4 milk fatty acid patterns: "MUFA and low SFA," "high n-6 PUFA," "high n-3 PUFA," and "high medium-chain fatty acids." In multivariable-adjusted analyses, fish oil supplementation and fatty cold water fish intake were positively associated with DHA and the "high n-3 PUFA" pattern. Mothers carrying the minor allele of FADS1-rs174556 had lower proportions of arachidonic acid (ARA; 20:4n-6). Independent of selected dietary variables and genetic variants, Asian ethnicity was associated with higher linoleic acid (18:2n-6) and total n-3 PUFAs. Ethnic differences in ARA were explained by FADS1 genotype. Maternal obesity was independently associated with higher total SFAs, the "high medium-chain fatty acid" pattern, and lower total MUFAs. Lactation stage, season, study site, and maternal education were also independently associated with some milk fatty acids. No associations were observed for maternal age, parity, delivery mode, or infant sex. CONCLUSIONS: This study provides unique insights about the "normal" variation in the composition of human milk fatty acids and the contributing dietary, genetic, sociodemographic, health, and environmental factors. Further research is required to assess implications for infant health.


Subject(s)
Fatty Acids/chemistry , Milk, Human/chemistry , Pregnancy/genetics , Adult , Alleles , Canada , Cohort Studies , Delta-5 Fatty Acid Desaturase , Demography , Diet , Environment , Fatty Acid Desaturases/genetics , Fatty Acid Desaturases/metabolism , Fatty Acids/metabolism , Female , Genotype , Humans , Infant , Lactation , Male , Maternal Nutritional Physiological Phenomena , Milk, Human/metabolism , Polymorphism, Single Nucleotide , Pregnancy/metabolism
6.
Clin Nutr ; 37(6 Pt A): 2230-2237, 2018 12.
Article in English | MEDLINE | ID: mdl-29153269

ABSTRACT

AIMS: To explore the relationship between vitamin D pathway genes, gene-environment interactions and vitamin D level among southeast Chinese pregnant women. METHODS: 759 participants from Zhoushan Pregnant Women Cohort (ZPWC) study, were enrolled from August 2011 to April 2014 in China. Plasma 25(OH)D levels and genetic variants in vitamin D pathway (NADSYN1/DHCR7, GC, CYP3A4, CYP2R1, CYP27A1, CYP27B1, VDR, CYP24A1, and LRP2) were measured using the blood sample collected at the first trimester. Information on demographics, lifestyle, and health behavior were collected using a questionnaire. Multilinear regression and logistic regression models were performed to estimate the associations between SNPs and 25(OH)D level. RESULTS: Mean plasma 25(OH)D concentrations were 15.6 ng/mL among the pregnant women. Variants of GC rs16846876, rs17467825, rs2282679, rs3755967, rs2298850, rs4588, rs7041 and rs1155563, CYP3A4 rs2242480 and CYP24A1 rs2209314 were significantly associated with both 25(OH)D concentrations and vitamin D deficiency (25(OH)D < 15 ng/mL). Variants of NADSYN1/DHCR7 were significantly associated with 25(OH)D concentrations among pregnant women without vitamin D supplements. Pregnant women with vitamin D binding protein (Gc) Gc-1f (P = 0.02) and Gc-1s (P = 0.005) had higher plasma 25(OH)D levels compared to women with Gc-2. Genotype risk score (GRS) calculated from rs7041, rs2242480 and rs2209314 shown a significantly negative association with 25(OH)D levels. Participants with GRS > 3 had a higher risk for vitamin D deficiency than individuals with GRS ≤ 3 (OR = 1.71, 95% CI = 1.25-2.35). Interactions between seasons and CYP27A1 rs933994, CYP3A4 rs2246709 on plasma 25(OH)D concentrations were also observed. Haplotypes of GC and LRP2 genes shown significant associations with 25(OH)D levels among pregnant women, respectively. CONCLUSIONS: Genetic mutants in vitamin D pathway (GC, CYP3A4, CYP24A1, and NADSYN1/DHCR7) had significant associations with 25(OH)D levels among pregnant women in southeast China. Furthermore, their associations were modified by vitamin D supplementation and season.


Subject(s)
Cytochrome P-450 Enzyme System/genetics , Polymorphism, Single Nucleotide/genetics , Pregnancy , Vitamin D-Binding Protein/genetics , Vitamin D/blood , Adult , China/epidemiology , Cohort Studies , Female , Humans , Pregnancy/blood , Pregnancy/genetics , Pregnancy/statistics & numerical data , Young Adult
7.
Nutrition ; 32(10): 1068-74, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27211082

ABSTRACT

OBJECTIVE: We investigated whether calcium plus vitamin D supplementation interacts with polymorphisms in the VDR gene promoter region to affect changes on maternal bone mass from 5 to 20 wk postpartum in Brazilian adolescent mothers. METHODS: Pregnant adolescents (14-19 y) randomly received calcium plus cholecalciferol (600 mg/d + 200 IU/d, n = 30) or placebo (n = 26) from 26 wk of pregnancy until parturition. Bone mineral content (BMC), bone area (BA), and bone mineral density (BMD) at total body, lumbar spine, total hip, and femoral neck were evaluated at 5 and 20 wk postpartum. Serum 25-hydroxyvitamin D (25[OH]D) and parathyroid hormone concentrations were measured. Real-time polymerase chain reaction was used for genotyping rs7139166 (1521 pb G > C) and rs4516035 (1012 pb A > G). Interactions between supplementation and polymorphisms were adjusted for significant covariates. RESULTS: Changes in serum 25(OH)D from pregnancy to postpartum differed between supplemented and placebo groups for mothers carrying 1521 GG/1012 AA genotypes (P = 0.004). Only in the placebo group, mothers carrying 1521 GG/1012 AA had greater reduction in total BMD z score, femoral neck BMC, and BMD from 5 to 20 wk postpartum compared with those with 1521 GC/1012 AG (P < 0.05). In the placebo group, total hip BA decreased from 5 to 20 wk postpartum in adolescents with 1521 GG/1012 AA, but increased in those with 1521 GC/1012 AG (P < 0.05), in contrast to the supplemented group. CONCLUSION: Calcium plus vitamin D supplementation during pregnancy interacted with polymorphisms in the VDR gene promoter region affecting postpartum bone loss. The increased supply of calcium and vitamin D appeared to minimize postpartum bone loss particularly in adolescents with 1521 GG/1012 AA.


Subject(s)
Bone Density/genetics , Bone and Bones/anatomy & histology , Calcium, Dietary/administration & dosage , Polymorphism, Single Nucleotide , Postpartum Period/genetics , Postpartum Period/physiology , Pregnancy/genetics , Pregnancy/physiology , Receptors, Calcitriol/genetics , Vitamin D/administration & dosage , Adolescent , Brazil , Cholecalciferol/administration & dosage , Female , Humans , Parathyroid Hormone/blood , Promoter Regions, Genetic , Young Adult
8.
Rev. fitoter ; 15(2): 133-146, dic. 2015. ilus, tab
Article in Spanish | IBECS | ID: ibc-147882

ABSTRACT

El uso de productos naturales ha impactado diversos aspectos de la medicina incluyendo la salud sexual y repreductiva, con efectos deletéreos sobre los espermatozoides o afrodisiacos Se ha evaluado el efecto de diversas plantas afrodisiacas sobre los mecanismos del desempeño sexual y la calidad de los espermatozoides, lo que permite plantear que extractos de las mismas podrian facilitar la capacitación espermática. En esta revisión bibliográfica se reportan los usos farmacológicos y tradicionales de 20 plantas consideradas tradicionalmente afrodisiacas que podrian ser utilizadas como agentes naturales con efecto capacitante sobre espermatozoides humanos (AU)


O uso de produtos naturais tem tido impacto em diversos aspectos da medicina, incluindo a saude sexual e reprodutiva, tanto pelos potenciais efeitos nocivos sobre os espermatozoides como atraves do use de afrodisiacos. Estudou-se o efeito de varias plantas afrodisiacas sobre os mecanismos de desempenho sexual e qualidade das células espermaticas, para avaliar a possibilidadede melhoria da capacitagao dos espermatozoides. Neste revisao da literatura sao relatados os uses farmacologicos e tradicionais de 20 plantas tradicionalmente consideradas afrodisiacas, que poderiam ser utilizadas como compostos naturais com efeito na capacitaçao de esperma humano (AU)


The use of natural products has impacted various aspects of medicine including sexual and reproductive health, through their deleterious effect on sperm cells or as aphrodisiacs. The mechanisms of sexual performance and sperm cells quality of several aphrodisiac plants have been studied, in order of evaluating the possibility of enhancing sperm capacitation. In this literature review, the pharmacological and traditional uses of 20 aphrodisiac plants that could be used as natural agents with effect on human sperm capacitation are reported (AU)


Subject(s)
Humans , Animals , Aphrodisiacs/agonists , Aphrodisiacs/chemical synthesis , Spermatozoa/cytology , Spermatozoa/physiology , Sexual Health , Reproductive Health/education , Reproductive Health/ethnology , Plants/anatomy & histology , Pregnancy/genetics , Therapeutics/methods , Aphrodisiacs/administration & dosage , Aphrodisiacs/adverse effects , Spermatozoa/abnormalities , Spermatozoa/classification , Reproductive Health/classification , Reproductive Health/trends , Plants/adverse effects , Pregnancy/metabolism , Therapeutics/standards
9.
Reproduction ; 148(6): 581-92, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25392189

ABSTRACT

Maternal one-carbon (1-C) metabolism provides methylgroups for fetal development and programing by DNA methylation as one of the underlying epigenetic mechanisms. We aimed to investigate maternal 1-C biomarkers, folic acid supplement use, and MTHFR C677T genotype as determinants of 1-C metabolism in early pregnancy in association with newborn DNA methylation levels of fetal growth and neurodevelopment candidate genes. The participants were 463 mother-child pairs of Dutch national origin from a large population-based birth cohort in Rotterdam, The Netherlands. In early pregnancy (median 13.0 weeks, 90% range 10.4-17.1), we assessed the maternal folate and homocysteine blood concentrations, folic acid supplement use, and the MTHFR C677T genotype in mothers and newborns. In newborns, DNA methylation was measured in umbilical cord blood white blood cells at 11 regions of the seven genes: NR3C1, DRD4, 5-HTT, IGF2DMR, H19, KCNQ1OT1, and MTHFR. The associations between the 1-C determinants and DNA methylation were examined using linear mixed models. An association was observed between maternal folate deficiency and lower newborn DNA methylation, which attenuated after adjustment for potential confounders. The maternal MTHFR TT genotype was significantly associated with lower DNA methylation. However, maternal homocysteine and folate concentrations, folic acid supplement use, and the MTHFR genotype in the newborn were not associated with newborn DNA methylation. The maternal MTHFR C677T genotype, as a determinant of folate status and 1-C metabolism, is associated with variations in the epigenome of a selection of genes in newborns. Research on the implications of these variations in methylation on gene expression and health is recommended.


Subject(s)
Carbon/metabolism , DNA Methylation/physiology , Infant, Newborn/metabolism , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Pregnancy/genetics , Pregnancy/metabolism , Adult , Cohort Studies , DNA/metabolism , Epigenesis, Genetic/physiology , Female , Fetal Development/physiology , Folic Acid/blood , Folic Acid/metabolism , Genotype , Homocysteine/blood , Humans , Male
10.
Nutrition ; 27(9): 925-30, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21367581

ABSTRACT

OBJECTIVE: The aim was to investigate whether pregnancy-induced changes in total homocysteine (tHcy) are associated with folate and vitamin B12 nutritional status, genetic C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) enzyme, and gestation outcome at a time when folic acid supplementation started to be recommended in the Spanish health system. METHODS: In total 154 pregnant women were recruited from among gynecologic patients of the Alcorcón Public Hospital Outpatient Clinic (Madrid, Spain). Blood tests were performed at weeks 15, 24, and 32 of pregnancy. Total Hcy, folate, and vitamin B12 serum fasting concentrations were measured using an IMx system. Genotype analyses were done by polymerase chain reaction/restriction fragment/length polymorphism analysis. RESULTS: Folate and vitamin B12 serum concentrations decreased significantly (P < 0.01) through pregnancy and reached the lowest values in the third trimester. Serum tHcy concentrations were significantly (P < 0.01) lower in the second trimester but increased in the third trimester. Frequencies of MTHFR C667T genotype were CC (35.7%), CT (57.2%), and TT (7.1%). Total Hcy concentration was not statistically influenced by maternal genotype. Plasma folate was the single negative predictor of maternal tHcy in the first trimester of pregnancy; 11.1% of gestations resulted in intrauterine growth restriction, 7.9% in gestational diabetes mellitus, and 4.8% in gestational hypertension. No significant differences in serum folate, vitamin B12, or tHcy concentrations were found in complicated pregnancies and these were unrelated to MTHFR genotype. CONCLUSION: Although tHcy seems to be physiologically low in this Spanish population and unrelated to folate and B12 nutritional status, C677T MTHFR genotype, and some pregnancy complications, we support the statement that appropriate folate concentration may be important throughout pregnancy to prevent abnormalities associated with altered status (e.g., neural tube defects). According to our study, supplementation with folic acid seems to achieve this purpose because diet alone may be insufficient. In addition, a poor vitamin B12 status, as measured by plasma levels, may indicate that supplementation of both vitamins is needed.


Subject(s)
Folic Acid/blood , Homocysteine/blood , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Polymorphism, Genetic , Pregnancy Complications/blood , Pregnancy/blood , Vitamin B 12/blood , Adult , Diabetes, Gestational/blood , Diabetes, Gestational/genetics , Dietary Supplements , Female , Fetal Growth Retardation/blood , Fetal Growth Retardation/genetics , Folic Acid/administration & dosage , Genotype , Humans , Hypertension, Pregnancy-Induced/blood , Hypertension, Pregnancy-Induced/genetics , Longitudinal Studies , Nutrition Policy , Pregnancy/genetics , Pregnancy Complications/genetics , Prevalence , Spain/epidemiology
11.
Epigenetics ; 6(1): 86-94, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20864804

ABSTRACT

Supplementation with folic acid during pregnancy is known to reduce the risk of neural tube defects and low birth weight. It is thought that folate and other one-carbon intermediates might secure these clinical effects via DNA methylation. We examined the effects of folate on the human methylome using quantitative interrogation of 27,578 CpG loci associated with 14,496 genes at single-nucleotide resolution across 12 fetal cord blood samples. Consistent with previous studies, the majority of CpG dinucleotides located within CpG islands exhibited hypo-methylation while those outside CpG islands showed mid-high methylation. However, for the first time in human samples, unbiased analysis of methylation across samples revealed a significant correlation of methylation patterns with plasma homocysteine, LINE-1 methylation and birth weight centile. Additionally, CpG methylation significantly correlated with either birth weight or LINE-1 methylation were predominantly located in CpG islands. These data indicate that levels of folate-associated intermediates in cord blood reflect their influence and consequences for the fetal epigenome and potentially on pregnancy outcome. In these cases, their influence might be exerted during late gestation or reflect those present during the peri-conceptual period.


Subject(s)
Birth Weight/physiology , Epigenesis, Genetic/physiology , Fetal Blood/metabolism , Homocysteine/blood , Long Interspersed Nucleotide Elements/physiology , Pregnancy/blood , Birth Weight/drug effects , CpG Islands/physiology , Epigenesis, Genetic/drug effects , Female , Folic Acid/administration & dosage , Gene Expression Profiling , Humans , Male , Neural Tube Defects/blood , Neural Tube Defects/genetics , Neural Tube Defects/prevention & control , Pregnancy/drug effects , Pregnancy/genetics , Vitamin B Complex/administration & dosage
12.
Am J Clin Nutr ; 92(2): 336-46, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20534746

ABSTRACT

BACKGROUND: Choline is essential for infant nutrition, and breast milk is a rich source of this nutrient. Common single nucleotide polymorphisms (SNPs) change dietary requirements for choline intake. OBJECTIVE: The aim of this study was to determine whether total choline intake and/or SNPs influence concentrations of choline and its metabolites in human breast milk and plasma. DESIGN: We gave a total of 103 pregnant women supplemental choline or a placebo from 18 wk gestation to 45 d postpartum and genotyped the women for 370 common SNPs. At 45 d postpartum, we measured choline metabolite concentrations in breast milk and plasma and assessed the dietary intake of choline by using a 3-d food record. RESULTS: On average, lactating women in our study ate two-thirds of the recommended intake for choline (Adequate Intake = 550 mg choline/d). Dietary choline intake (no supplement) correlated with breast-milk phosphatidylcholine and plasma choline concentrations. A supplement further increased breast-milk choline, betaine, and phosphocholine concentrations and increased plasma choline and betaine concentrations. We identified 5 SNPs in MTHFR that altered the slope of the intake-metabolite concentration relations, and we identified 2 SNPs in PEMT that shifted these curves upward. Individuals who shared sets of common SNPs were outliers in plots of intake-metabolite concentration curves; we suggest that these SNPs should be further investigated to determine how they alter choline metabolism. CONCLUSION: Total intake of choline and genotype can influence the concentrations of choline and its metabolites in the breast milk and blood of lactating women and thereby affect the amount of choline available to the developing infant. This study was registered at clinicaltrials.gov as NCT00678925.


Subject(s)
Choline/metabolism , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Milk, Human/chemistry , Phosphatidylethanolamine N-Methyltransferase/genetics , Polymorphism, Single Nucleotide , Adult , Betaine/analysis , Betaine/blood , Choline/administration & dosage , Choline/analysis , Diet , Diet Records , Dietary Supplements , Female , Genotype , Humans , Lactation , Maternal Nutritional Physiological Phenomena , Nutrition Policy , Phosphatidylcholines/analysis , Phosphorylcholine/analysis , Pregnancy/blood , Pregnancy/genetics , Young Adult
13.
J Biol Chem ; 284(4): 1982-9, 2009 Jan 23.
Article in English | MEDLINE | ID: mdl-19001366

ABSTRACT

Choline is an essential nutrient that, via its metabolite betaine, serves as a donor of methyl groups used in fetal development to establish the epigenetic DNA and histone methylation patterns. Supplementation with choline during embryonic days (E) 11-17 in rats improves memory performance in adulthood and protects against age-related memory decline, whereas choline deficiency impairs certain cognitive functions. We previously reported that global and gene-specific DNA methylation increased in choline-deficient fetal brain and liver, and these changes in DNA methylation correlated with an apparently compensatory up-regulation of the expression of DNA methyltransferase Dnmt1. In the current study, pregnant rats were fed a diet containing varying amounts of choline (mmol/kg: 0 (deficient), 8 (control), or 36 (supplemented)) during E11-17, and indices of histone methylation were assessed in liver and frontal cortex on E17. The mRNA and protein expression of histone methyltransferases G9a and Suv39h1 were directly related to the availability of choline. DNA methylation of the G9a and Suv39h1 genes was up-regulated by choline deficiency, suggesting that the expression of these enzymes is under negative control by methylation of their genes. The levels of H3K9Me2 and H3K27Me3, tags of transcriptionally repressed chromatin, were up-regulated by choline supplementation, whereas the levels of H3K4Me2, associated with active promoters, were highest in choline-deficient rats. These data show that maternal choline supply during pregnancy modifies fetal histone and DNA methylation, suggesting that a concerted epigenomic mechanism contributes to the long term developmental effects of varied choline intake in utero.


Subject(s)
Brain/metabolism , Choline/metabolism , Histone-Lysine N-Methyltransferase/metabolism , Histones/metabolism , Liver/metabolism , Methyltransferases/metabolism , Pregnancy/metabolism , Repressor Proteins/metabolism , Animals , Brain/embryology , CpG Islands/genetics , Female , Fetus/embryology , Fetus/metabolism , Gene Expression Regulation, Developmental , Gene Expression Regulation, Enzymologic , Histone-Lysine N-Methyltransferase/genetics , Liver/embryology , Methylation , Methyltransferases/genetics , Pregnancy/genetics , Promoter Regions, Genetic/genetics , Rats , Repressor Proteins/genetics
14.
CES med ; 22(2): 57-67, jul.-dic. 2008. tab
Article in Spanish | LILACS | ID: lil-565188

ABSTRACT

La preeclampsia es un trastorno hipertensivo específico del embarazo y es una de las principales causas de morbilidad y mortalidad materna y neonatal en todo el mundo, afectando 5 a 7% de todos los embarazos. En Colombia es la primera causa de morbilidad y mortalidad materna, siendo un problema de salud pública. Muchas investigaciones coinciden en que su origen se relaciona con la interacción entre factores genéticos y ambientales. Múltiples estudios han explorado factores genéticos tratando de identificar regiones cromosómicas y genes candidatos cuyas variantes se relacionen con una mayor susceptibilidad a la enfermedad. La presente revisión ofrece una visión general de los factores genéticos asociados a la preeclampsia.


Preeclampsia is a hypertensive disorder that occurs only during pregnancy and is one of the main causes of maternal and neonatal morbidity and mortality, affecting 5-7% of pregnancies. In Colombia it is the primary cause of maternal morbidity and mortality, and an important public health issue. Many investigations agree that its origin is related to the interaction of genetic and environmental factors. Numerous studies have explored genetic factors in attempt to identify chromosomal regions and candidate genes, variants of which are related with increased susceptibility to the disease. This review offers a general vision of the genetic factors associated with preeclampsia.


Subject(s)
Humans , Genetics/history , Homeopathic Pathogenesy , Pre-Eclampsia/genetics , Pre-Eclampsia/history , Pre-Eclampsia/therapy , Pregnancy/genetics , Polymorphism, Genetic
15.
Pediatr. aten. prim ; 8(31): 505-521, jul.-sept. 2006. ilus, tab
Article in Spanish | IBECS | ID: ibc-140436

ABSTRACT

Este artículo muestra ideas clave para incluir en los contenidos de los programas de educación para la salud sobre afectividad y sexualidad, normalmente dirigidos a adolescentes, pero que también tienen una acogida excelente entre los adultos. Actualmente se plantea una reflexión importante más allá de la idea clásica de educar para evitar embarazos no deseados y enfermedades de transmisión sexual: el sexo es una fuerza positiva y enriquecedora de la vida humana que contribuye a nuestro proceso de crecimiento personal como seres completos (cuerpo + energía + emociones + mente + alma). Es la salud sexual desde el punto de vista holístico (total), la salud como máximo desarrollo de la persona (AU)


This article shows key ideas to include in the contents of the programs of health education on affectivity and sexuality, normally directed to teenagers, but that also have an excellent reception among the adults. Nowadays an important reflection appears beyond the classic idea of educating to avoid not wished pregnancies and diseases of sexual transmission: sex is a positive and enriching force of human life that contributes to our process of personal growth as complete beings (body + energy + emotions + mind + soul). It is the sexual health from the holistic (total) point of view, health as the greatest development of the person (AU)


Subject(s)
Adolescent , Child , Infant, Newborn , Humans , Health Education , Health Education , Sexually Transmitted Diseases/congenital , Sexually Transmitted Diseases/genetics , Pregnancy/metabolism , Pregnancy/psychology , Health Education/classification , Health Education/methods , Sexually Transmitted Diseases/metabolism , Sexually Transmitted Diseases/pathology , Pregnancy/blood , Pregnancy/genetics , Communication/history , Sex
16.
Adv Exp Med Biol ; 478: 41-55, 2000.
Article in English | MEDLINE | ID: mdl-11065059

ABSTRACT

For each individual, the genetic endowment at conception sets the limits on the capacity or metabolic function. The extent to which this capacity is achieved or constrained is determined by the environmental experience. The consequences of these experiences tend to be cumulative throughout life and express themselves phenotypically as achieved growth and body composition, hormonal status and the metabolic capacity for one or other function. At any time later in life the response to an environmental challenge, such as stress, infection or excess body weight is determined by an interaction amongst these factors. When the metabolic capacity to cope is exceeded, the limitation in function is exposed and expresses itself as overt disease. During early life and development the embryo, fetus and infant are relatively plastic in terms of metabolic function. The effect of any adverse environmental exposure is likely to be more marked than at later ages and the influence is more likely to exert a fundamental effect on the development of metabolic capacity. This has been characterised as "programming" and has come to be known as "the Barker hypothesis" or "the fetal origins hypothesis". Barker has shown that the size and shape of the infant at birth has considerable statistical power to predict the risk of chronic disease in later life. These relationships are graded and operate across a range of birth weight, which would generally be considered to be normal, and are not simply a feature of the extreme of growth retardation. The first evidence showed strong relations between birth weight and heart disease, the risk factors for heart disease, diabetes and hypertension, and the intermediary markers for heart disease, blood cholesterol and fibrinogen. Strong associations have also been found for bone disease, allergic disease and some aspects of brain function. In experimental studies in animals it is possible to reproduce all of the metabolic features predicted from this hypothesis by moderating the consumption of food, or its pattern during pregnancy, and determining metabolic behaviour in the offspring. It has been shown that aspects of maternal diet exert an influence on fetal growth, especially the dietary intake of carbohydrate, protein and some micronutrients. However, these relationships are less strong than might have been predicted, especially when compared with the associations which can be drawn with maternal shape, size and metabolic capacity. Maternal height, weight and body composition relate to the metabolic capacity of the mother and her ability to provide an environment in which the delivery of nutrients to the fetus is optimal. Current evidence suggests that the size of the mothers determines her ability to support protein synthesis, and that maternal protein synthesis, especially visceral protein synthesis, is very closely related to fetal growth and development. It is not clear the extent to which the effect of an adverse environment in utero can be reversed by improved conditions postnatally, but some care is needed in exploring this area, as the evidence suggests that "catch-up" growth imposes its own metabolic stress and may in itself exert a harmful effect.


Subject(s)
Energy Metabolism/physiology , Infant Nutritional Physiological Phenomena , Infant, Newborn/metabolism , Nutritional Physiological Phenomena , Pregnancy/physiology , Adaptation, Biological , Amino Acids/metabolism , Animals , Birth Weight/physiology , Body Composition/genetics , Body Composition/physiology , Child Development/physiology , Chronic Disease , Embryonic and Fetal Development/physiology , Female , Growth/physiology , Humans , Models, Animal , Pregnancy/genetics , Pregnancy/metabolism
17.
Am J Chin Med ; 20(1): 75-82, 1992.
Article in English | MEDLINE | ID: mdl-1605131

ABSTRACT

To provide some insights how herbal medicines affect deoxyribonucleic acid (DNA) synthesis in the uterus, the DNA polymerase activities (alpha and beta) in uterine samples taken from rats were measured. DNA polymerase alpha activity with respect to DNA content revealed alpha cyclic change with the highest level on proestrus, while DNA polymerase beta activity showed no significant changes during the estrous cycle. The increased period of the activity coincided with that of 17 beta-estradiol (E2) but not progesterone (P4) in the blood. Injection of 10 IU pregnant mare serum gonadotropin (PMS) on day 27 of age gradually increased DNA polymerase alpha activity in uteri, while concomitant treatment with PMS and 200 micrograms Tokishakuyakusan (TS), Keishibukuryogan (KB) or Unkeito (UT) suppressed the enzyme activity, with a most remarkable effect of KB. These results suggest that TS, KB or UT suppresses in vivo DNA polymerase alpha activity induced by PMS in the rat uterus.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , DNA-Directed DNA Polymerase/drug effects , Drugs, Chinese Herbal/pharmacology , Pregnancy/drug effects , Uterus/drug effects , Animals , DNA/analysis , DNA/biosynthesis , DNA/drug effects , DNA Replication/drug effects , DNA-Directed DNA Polymerase/analysis , Drug Evaluation, Preclinical , Estradiol/blood , Female , Gonadotropins, Equine/pharmacology , Pregnancy/blood , Pregnancy/genetics , Progesterone/blood , Protein Biosynthesis , Rats , Rats, Inbred Strains , Transcription, Genetic
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