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MicroRNAs： crucial modulators of fetal epigenetic programming in nutrition and glucose metabolism

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Chinese Medical Journal 2014年第20期127卷 3521-3523页

作者： Xiao Xinhua Zheng Jia Department of Endocrinology Key Laboratory of EndocrinologyMinistry of Health Peking Union Medical College Hospital DiabetesResearch Center of Chinese Academy of Medical Sciences & PekingUnion Medical College Beijing 100730 China

It is generally believed that genotype and adult lifestyle elements are primary risks of diabetes mellitus. However, increasing evidence demonstrates that early life malnutrition during the period of gestation and/or lactation may increase our susceptibility to some metabolic diseases in later life and the underlying mechanism is not very clear. Recently, epigenetics is hypothesized to be the important molecular basis of the imbalanced early life nutrition and glucose metabolism disorders. The fundamental mechanism is that early developmental nutrition can regulate epigenetic modifications of some genes associated with development and metabolism. MicroRNAs （miRNAs） are recognized as an important epigenetic modification and they are a major class of small noncoding RNAs （about 20-22 nucleotides） which can mediate posttranscriptional regulation of target genes with cell differentiation and apoptosis. Recent studies suggest that miRNAs may be the crucial modulators of fetal epigenetic programming in nutrition and metabolic disorders. How miRNAs can modulate the relationship between early life nutrition and disease susceptibilities, especially for aberrant glucose metabolism？

关键词： mieroRNAs epigenetics fetal programming nutrition glucose metabolism

Stage-specific nutritional management and developmental programming to optimize meat production

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Journal of Animal Science and Biotechnology 2023年第2期14卷 451-464页

作者： Liang Zhao Xiangdong Liu Noe A Gomez Yao Gao Jun Seok Son Song Ah Chae Mei‑Jun Zhu Min Du College of Animal Science and Technology Nanjing Agricultural University210095 NanjingPR China Nutrigenomics and Growth Biology Laboratory Department of Animal SciencesWashington State UniversityWA 99164 PullmanUSA Laboratory of Perinatal Kinesioepigenetics Department of ObstetricsGynecology and Reproductive SciencesUniversity of Maryland School of MedicineMD 21201 BaltimoreUSA School of Food Science Washington State UniversityWAPullmanUSA.

Over the past few decades,genetic selection and refined nutritional management have extensively been used to increase the growth rate and lean meat production of livestock.However,the rapid growth rates of modern breeds are often accompanied by a reduction in intramuscular fat deposition and increased occurrences of muscle abnor‑malities,impairing meat quality and processing functionality.Early stages of animal development set the long‑term growth trajectory of offspring.However,due to the seasonal reproductive cycles of ruminant livestock,gestational nutrient deficiencies caused by seasonal variations,frequent droughts,and unfavorable geological locations nega‑tively affect fetal development and their subsequent production efficiency and meat quality.Therefore,enrolling live‑stock in nutritional intervention strategies during gestation is effective for improving the body composition and meat quality of the offspring at harvest.These crucial early developmental stages include embryonic,fetal,and postnatal stages,which have stage‑specific effects on subsequent offspring development,body composition,and meat quality.This review summarizes contemporary research in the embryonic,fetal,and neonatal development,and the impacts of maternal nutrition on the early development and programming effects on the long‑term growth performance of livestock.Understanding the developmental and metabolic characteristics of skeletal muscle,adipose,and fibrotic tissues will facilitate the development of stage‑specific nutritional management strategies to optimize production efficiency and meat quality.

关键词： Adipose tissue Embryonic development fetal programming Fibro/adipogenic progenitors Marbling Nutritional regulations Skeletal muscle

Paternal physical exercise modulates global DNA methylation status in the hippocampus of male rat offspring

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Neural Regeneration Research 2019年第3期14卷 491-500页

作者： Christiano Spindler Ethiane Segabinazi Andre Luis Ferreira de Meireles Francele Valente Piazza Filipe Mega Gabriela dos Santos Salvalaggio Matilde Achaval Viviane Rostirola Elsner Simone Marcuzzo Programa de Pos-Graduacao em Neurociencias Instituto de Ciencias Basicas da Saude Universidade Federal do Rio Grande do Sul Laboratorio de Histofisiologia Comparada Departamento de Ciencias Morfologicas Instituto de Ciencias Basicas da Saude Universidade Federal do Rio Grande do Sul Programa de Pos-Graduacao em Biociências e Reabilitacao Centro Universitario Metodista-IPA

It is widely known that maternal physical exercise is able to induce beneficial improvements in offspring cognition; however, the effects of paternal exercise have not been explored in detail. The present study was designed to evaluate the impact of paternal physical exercise on memory and learning, neuroplasticity and DNA methylation levels in the hippocampus of male offspring. Adult male Wistar rats were divided into two groups: sedentary or exercised fathers. The paternal preconception exercise protocol consisted of treadmill running, 20 minutes daily, 5 consecutive days per week for 22 days, while the mothers were not trained. After mating, paternal sperm was collected for global DNA methylation analysis. At postnatal day 53, the offspring were euthanized, and the hippocampus was dissected to measure cell survival by 5-bromo-2′-deoxiuridine and to determine the expression of synaptophysin, reelin, brain-derived neurotrophic factor and global DNA methylation levels. To measure spatial memory and learning changes in offspring, the Morris water maze paradigm was used. There was an improvement in spatial learning, as well as a significant decrease in hippocampal global DNA methylation levels in the offspring from exercised fathers compared with those from sedentary ones; however, no changes were observed in neuroplasticity biomarkers brain-derived neurotrophic factor, reelin and 5-bromo-2′-deoxiuridine. Finally, the global DNA methylation of paternal sperm was not significantly changed by physical exercise. These results suggest a link between paternal preconception physical activity and cognitive benefit, which may be associated with hippocampal epigenetic programming in male offspring. However, the biological mechanisms of this modulation remain unclear.

关键词： epigenetics preconception methylation learning treadmill running fetal programming inheritance sperm nerve regeneration

Effects of supplements differing in fatty acid profile to late gestational beef cows on cow performance,calf growth performance,and mRNA expression of genes associated with myogenesis and adipogenesis

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Journal of Animal Science and Biotechnology 2021年第4期12卷 1483-1497页

作者： Taoqi Shao Frank A.Ireland Joshua C.McCann Daniel W.Shike Department of Animal Sciences University of Illinois at Urbana-ChampaignUrbanaILUSA

Background:Maternal nutrition during gestation affects fetal development,which has long-term programming effects on offspring postnatal growth performance.With a critical role in protein and lipid metabolism,essential fatty acids can influence the development of muscle and adipose tissue.The experiment investigated the effects of late gestation supplements(77 d prepartum),either rich in saturated and monounsaturated fatty acids(CON;155 g/cow/d EnerGII)or polyunsaturated fatty acids(PUFA;80 g/cow/d Strata and 80 g/cow/d Prequel),on cow performance and subsequent calf growth performance as well as mRNA expression in longissimus muscle(LM)and subcutaneous adipose tissue at birth and weaning.Results:There was no difference(P≥0.34)in cow body weight(BW)or body condition score from presupplementation through weaning.Relative concentrations of C18:3n-3 and C20:4n-6 decreased(P≤0.05)to a greater extent from mid-supplementation to calving for PUFA compared with CON cows.Cow plasma C20:0,C20:5n-3,and C22:6n-3 were increased(P≤0.01)in PUFA during supplementation period.At birth,PUFA steers had greater(P=0.01)plasma C20:5n-3.No differences(P≥0.33)were detected in steer birth BW or dam milk production,however,CON steers tended(P=0.06)to have greater pre-weaning average daily gain and had greater(P=0.05)weaning BW compared with PUFA.For mRNA expression in steers:MYH7 and C/EBPβin LM increased(P≤0.04)to a greater extent from birth to weaning for PUFA compared with CON;MYF5 in LM and C/EBPβin adipose tissue tended(P≤0.08)to decrease more from birth to weaning for CON compared with PUFA;SCD in PUFA adipose tissue tended(P=0.08)to decrease to a greater extent from birth to weaning than CON.In addition,maternal PUFA supplementation tended(P=0.08)to decrease MYOG mRNA expression in LM and decreased(P=0.02)ZFP423 in adipose tissue during the pre-weaning stage.Conclusions:Late gestation PUFA supplementation decreased pre-weaning growth performance of the subsequent steer progeny compared with CON supplementation,which could have been

关键词： Beef cattle Fatty acids fetal programming Late gestation mRNA expression

Effects of maternal dietary omega-3 polyunsaturated fatty acids and methionine during late gestation on fetal growth,DNA methylation,and mRNA relative expression of genes associated with the inflammatory response,lipid metabolism and DNA methylation in placenta and offspring’s liver in sheep

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Journal of Animal Science and Biotechnology 2021年第2期12卷 611-625页

作者： Milca Rosa Velazquez Fernanda Batistel Juan Manuel Pinos Rodriguez Alejandro Enrique Relling Facultad de Medicina Veterinaria y Zootecnia Universidad Veracruzana91710 VeracruzMexico Department of Animal Science Ohio Agricultural Research and Development Center(OARDC)The Ohio State University114 Gerlaugh Hall1680 Madison AveWoosterOH 44691USA Department of Animal Dairy and Veterinary SciencesUtah State UniversityLoganUT 84322USA

Background:Omega-3 PUFA or methionine(Met)supply during gestation alters offspring physiology.However,the effect of both nutrients on fetal development has not been explored.Our objective was to determine the effects of supplementation of these two nutrients during late gestation on fetal growth,DNA methylation,and mRNA expression of genes associated with the inflammatory response,and DNA methylation.Ewes(n=5/treatment)were fed from day 100 to 145 of gestation one of the following treatments:1)basal diet(NS)without fatty acids(FS)or methionine(MS)supplementation;2)FS(10 g/kg Ca salts,source omega-3 PUFA);3)MS(1 g/kg rumen protected methionine);and 4)FS and MS(FS-MS).On day 145,ewes were euthanized,and data from dams and fetus was recorded.Placenta(cotyledon),fetal liver,and blood samples were collected.Results:A treatments interaction on fetal liver weight,ewe body weight and body condition score(BCS)was observed;FS-MS were heavier(Pfetal liver global DNA methylation increased(Pfetal liver,FS increased(P=0.04)the mRNA relative expression of arachidonate-5-lipoxygenase-activatingprotein and tended to decrease(P=0.06)methionine-adenosyltransferase-1A.Moreover,MS decreased(P=0.04)DNA-methyltransferase-1 and tended to decrease(P=0.08)free-fatty-acid-receptor-1 mRNA relative expression.Furthermore,FS-MS decreased mRNA relative expression of tumor-necrosis-factor-alpha(P=0.05),peroxisomeproliferator-activated-receptor-delta(P=0.03)and gamma(P=0.04),tended to decrease(P≤0.09)interleukin-6,fatty-acid-transport-protein-1,and delta-5-desaturase,and increased adenosylhomocysteinase(P=0.04)mRNA relative expression.In cotyledon,FS tended to decrease fatty acid binding protein 4(P=0.09)mRNA relative expression.Conclusion:Omega-3 PUFA and Met supplementation improves dam’s performance in lat

关键词： Fat supplementation fetal programming Maternal nutrition Nutrients Rumen protected methionine

Effect of gestational protein restriction on left ventricle hypertrophy and heart angiotensin II signaling pathway in adult offspring rats

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Health 2013年第4期5卷 78-84页

作者： Renan Brisolla da Silva Flavia Fernandes Mesquita Marilia Andreo Heloisa Balan Assalin Jose Antonio Rocha Gontijo Patricia Aline Boer fetal programming Laboratory Department of MorphologyBotucatu Bioscience InstituteUNESP-Sao Paulo State UniversityBotucatuBrazil Hydro-Saline Metabolism Laboratory Internal Medicine DepartmentFaculty of Medical SciencesState University of CampinasCampinasBrazil

Maternal protein restriction may be a risk factor for cardiovascular disorders in adulthood. The RAS (renin-angiotensin-system) plays a pivotal role in cardiac remodeling. Components of the RAS, including angiotensin II (AngII) and its receptors type 1 (AT1R) and 2 (AT2R) are expressed in the heart. This study investigates whether gestational protein restriction alters the expression and localization of AT1R and AT2R and RAS signaling pathway proteins in parallel with left ventricle hypertrophy and systemic hypertension in male offspring. Dams were kept on normal (NP, 17% protein) or low (LP, 6% protein) protein diet during pregnancy. Systolic blood pressure (SBP) of male offspring was measured from the 8th to 16th week and left ventricles of 16-wk-old rats were processed for histology, morphometric, immunoblotting and immunohistochemistry. LP offspring showed a significant reduction in birth body weight and SBP increased significantly from the 8th week. Left ventricle mass and cardiomyocytes area were also significantly higher in LP animals. Widespread perivascular fibrosis was not detected in the heart tissue. Analysis by immunoblotting and immunohistochemistry demonstrated a significant enhance in cardiomyocyte expression of AT1R and ERK1 in LP offspring. Expression of PI3K in LP was significantly reduced in cardiomyocytes and in the intramural coronary wall, while AT2R expression was unchanged in the NP group. We also found reduced LP expression of JAK2 and STAT3. In conclusion, our data also suggest that changes in the RAS may play a role in the ventricular growth through upregulation of the AT1-mediated ERK1/2 response, despite unchanged AT2R expression.

关键词： Low Birth Weight Arterial Hypertension fetal programming Protein Restriction Angiotensin II Left Ventricle Hypertrophy Cardiovascular Disease

Cardioprotective and renoprotective effects of Cocos nucifera water in offspring of high fat diet fed Wistar rat dams

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Journal of Coastal Life Medicine 2016年第8期4卷 634-638页

作者： Olufadekemi Tolulope Kunle-Alabi Opeyemi Oreofe Akindele Yinusa Raji Laboratoryfor Reproductive Physiology and Developmental programming Department of PhysiologyFaculty of Basic Medical SciencesCollege ofMedicineUniversity of IbadanIbadanNigeria

Objective:To evaluate the effects of Cocos nucifera(C.nucifera)water on the cardiovascular and renal functions of offspring from rat dams fed high fat diet during gestation.Methods:Four groups of pregnant Wistar rats were treated from gestation day 1 to 21;namely,control(1 mL/100 g distilled water),C.nucifera water(1 mL/100 g C.nucifera water),high fat diet(1 mL/100 g distilled water+30%butter:70%standard rodent diet)and high fat diet+C.nucifera water(1 mL/100 g C.nucifera water+30%butter:70%standard rodent diet).All dams received standard rodent diet from gestation day 22,and offspring were weaned to standard rodent diet on postnatal day 28.On postnatal day 120,serum and cardiac levels of malondialdehyde,interleukin-1βand high sensitivity C-reactive protein were determined in offspring.Serum creatinine and urea levels as well as histology of heart and kidney tissue were assessed.Data were analyzed using One-way ANOVA and P<0.05 was considered statistically significant.Results:Male high fat diet offspring showed significantly increased(P<0.05)serum interleukin-1βcompared with C.nucifera water offspring.The increase in serum high sensitivity C-reactive protein observed in female high fat diet offspring was not present in high fat diet+C.nucifera water offspring.Heart tissues from high fat diet offspring showed scanty fibers and congested myocardium with mild fibrosis.Male high fat diet offspring kidneys showed mesangial cell hyperplasia,fat infiltration and mild tubular necrosis.These were accompanied with alterations in serum urea and creatinine levels in high fat diet+C.nucifera water offspring.Conclusions:C.nucifera water exerts cardioprotective and renoprotective effects on offspring of rat dams fed high fat diet during gestation via an anti-inflammatory mechanism.

关键词： fetal programming Coconut water Fat Kidney Heart

Implications for heart disease development following obesity:maternal nutrient restriction increases ectopic lipid deposition in left ventricle

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Implications for heart disease development following obesity...

Parental renovascular hypertension-induced autonomic dysfunction in offspring is improved by prenatal or postnatal treatment with hydrogen sulfide

2008北京国际生理科学学术大会

作者： CHANLLY HYATT MA SEBERT S BUDGE H STEPHENSON T SYMONDS ME GARDNER DS Centre for Reproduction and Early Life Schools of Human DevelopmentUniversity HospitalNottinghamNG7 2UH Centre for Reproduction and Early Life Schools of Veterinary Medicine and ScienceUniversity of NottinghamSutton BoningtonLE12 5RD

Aims:Maternal nutrient restriction(NR)is associated with development of hypertension and heart disease later in life.We have previously shown that maternal NR coincident with early kidney development prevents the adverse molecular but not systemic renal effects of obesity.In the heart,maternal NR increasesβ-adrenergic receptor expression in juvenile obesity.The present study further investigate mRNA abundance of key genes involved in energy homeostasis,together with triglyceride content in obese offspring born to control fed and nutrient restricted mother.Study design:Welsh Mountain Sheep(n=21)were either NR(i.***.fed 50%less than controls) between early-to-mid(30-80d)gestation,or fed a control diet through pregnancy.From weaning to 12 months of age,offspring were either maintained out to pasture with unrestricted physical activity(Lean,L),or group-housed within a barn in order to restrict their activity and provided with ad libitum access to hay and concentrate pellets (Obese,O;NR obese,NRO).At 12 months the left ventricle was sampled and snap frozen for real-time PCR analysis.Tissue lipid was extracted by Fotch method followed by triglyceride assay.Results:Obesity resulted in left ventricular hypertrophy in conjunction with higher mRNA abundance for both FABP3 and PPARγ2 relative to lean sheep(P<0.05).Maternal nutrient restriction increased triglyceride accumulation and ACC mRNA expression, as well as reduced mRNA abundance of FABP3,Glut 1 and PPARγ2(P<0.05).Within NRO group,mRNA expression of AMPKα2 was positively correlated with triglyceride content(r=0.567,P<0.05).Conclusions:Both AMPK and ACC participate in metabolic switch in energy production,together with increased triglyceride content in left ventricle and decreased FABP3 expression.The results suggest that maternal NR elicited early-onset ectopic lipid infiltration in the heart following obesity.The increased lipid accumulation in maternal NR heart and thus predisposition to cardiovascular disease in adulthood may stem from impaired fuel mobilization and

关键词： maternal nutrient restriction obesity heart disease fetal programming

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Parental renovascular hypertension-induced autonomic dysfunc...