scholarly journals Maternal Undernutrition Alters The Skeletal Muscle Development and Methylation of Myogenic Factors in Progeny: A Randomized Controlled Trial

2021 ◽  
Author(s):  
Xiaoling Zhou ◽  
Qiongxian Yan ◽  
Liling Liu ◽  
Genyuan Chen ◽  
Shaoxun Tang ◽  
...  
Keyword(s):  
Muscle Development ◽  
Epigenetic Modification ◽  
Fiber Type ◽  
Controlled Trial ◽  
Promoter Regions ◽  
Maternal Undernutrition ◽  
Fiber Area ◽  
Cpg Site ◽  
Myogenic Factors ◽  
Femoris Muscle

Abstract Maternal malnutrition alters protein synthesis and muscle development in offspring. Epigenetic modification is one of the mechanisms involved in this developmental programming. However, the role of the methylation of myogenic factors remains unclear. Twenty-four pregnant goats were assigned to a control (100% of the nutrients requirement, n = 12) or a restricted group (60% of the nutrients requirement, n = 12) between 0.3 and 0.7 gestation (G). Descendants were harvested at 0.7 G and at 91 days after birth to analyze the fiber area and fiber type of femoris muscle and to examine the effects on the mTOR signal pathway and methylation of the promoter regions of myogenic factors. Maternal undernutrition increased the fiber area of the vastus muscle in the fetuses (P < 0.05). Undernutrition enhanced (P < 0.01) the proportions of MyHCI and MyHCIIA fibers in the vastus muscle of fetuses and semitendinosus (ST) muscle of kids, while the proportion of MyHCIIX fibers were decreased (P < 0.01) in the restricted fetuses and kids. The mRNA expression levels of EYA1 and MYOZ2 in the restricted fetuses were downregulated (P < 0.05), but no difference was observed in the restricted kids (P > 0.05). The percentage of DNA methylation at the + 530 CpG site of the MYF5 gene in the restricted fetuses was increased (P < 0.05), but the methylation percentages of the MYF5 gene at the +274,280 CpG site and of the MYOD gene at the +252 CpG site in the restricted kids were reduced (P < 0.05). The mTOR protein signals were downregulated (P < 0.05) in the restricted fetuses and kids. These results indicated that maternal undernutrition altered the fiber type of femoris muscle in offspring, but its relationship with the methylation in the promoter regions of myogenic genes needs to be further studied.

scholarly journals Rbfox1 is required for myofibril development and maintaining fiber type–specific isoform expression in Drosophila muscles

2022 ◽  
Vol 5 (4) ◽  
pp. e202101342
Author(s):  
Elena Nikonova ◽  
Amartya Mukherjee ◽  
Ketaki Kamble ◽  
Christiane Barz ◽  
Upendra Nongthomba ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Muscle Development ◽  
Rna Binding ◽  
Troponin I ◽  
Rna Binding Proteins ◽  
Fiber Type ◽  
Structural Defects ◽  
Specific Gene ◽  
Fiber Types ◽  
Isoform Expression

Protein isoform transitions confer muscle fibers with distinct properties and are regulated by differential transcription and alternative splicing. RNA-binding Fox protein 1 (Rbfox1) can affect both transcript levels and splicing, and is known to contribute to normal muscle development and physiology in vertebrates, although the detailed mechanisms remain obscure. In this study, we report that Rbfox1 contributes to the generation of adult muscle diversity in Drosophila. Rbfox1 is differentially expressed among muscle fiber types, and RNAi knockdown causes a hypercontraction phenotype that leads to behavioral and eclosion defects. Misregulation of fiber type–specific gene and splice isoform expression, notably loss of an indirect flight muscle–specific isoform of Troponin-I that is critical for regulating myosin activity, leads to structural defects. We further show that Rbfox1 directly binds the 3′-UTR of target transcripts, regulates the expression level of myogenic transcription factors myocyte enhancer factor 2 and Salm, and both modulates expression of and genetically interacts with the CELF family RNA-binding protein Bruno1 (Bru1). Rbfox1 and Bru1 co-regulate fiber type–specific alternative splicing of structural genes, indicating that regulatory interactions between FOX and CELF family RNA-binding proteins are conserved in fly muscle. Rbfox1 thus affects muscle development by regulating fiber type–specific splicing and expression dynamics of identity genes and structural proteins.

The effect of maternal undernutrition on muscle fibre type in the newborn lamb

2003 ◽  
Vol 2003 ◽  
pp. 60-60
Author(s):  
A.J. Fahey ◽  
J.M. Brameld ◽  
T. Parr ◽  
P.J. Buttery
Keyword(s):  
Muscle Fibre ◽  
Meat Quality ◽  
Fibre Type ◽  
Muscle Development ◽  
Nutrient Supply ◽  
Muscle Fibre Type ◽  
Growth Potential ◽  
Muscle Fibres ◽  
General Hypothesis ◽  
Maternal Undernutrition

Muscle fibre type can influence meat quality (Maltinet al1997). Muscle fibre formation occurs during gestation and in the sheep the total number of fibres in a muscle is essentially fixed at birth. (Ashmereet al1972). Postnatal growth of muscle is entirely due to elongation and widening of the existing muscle fibres. Therefore the gestational period is important in the long-term growth potential of the animal. By investigating changes in muscle fibre type, the aim of this study was to test the general hypothesis that the poor carcass quality sometimes seen in ruminant animals may be due to poor nutrition at strategic time points during the animal’s development. As agricultural practices continue to become more extensive, variation in the nutrient supply to the animal is becoming more common. Therefore it is important to understand the effect of any changes in nutrient supply to the mother, during gestation on the subsequent muscle development of the fetus and ultimately the effects on meat quality.

A role for poly(ADP-ribosyl)ation in DNA methylation

2003 ◽  
Vol 81 (3) ◽  
pp. 197-208 ◽  
Author(s):  
Giuseppe Zardo ◽  
Anna Reale ◽  
Giovanna De Matteis ◽  
Serena Buontempo ◽  
Paola Caiafa
Keyword(s):  
Dna Methylation ◽  
Gene Silencing ◽  
Control Mechanism ◽  
Epigenetic Modification ◽  
Housekeeping Genes ◽  
Promoter Regions ◽  
Epigenetic Events ◽  
Aberrant Dna Methylation ◽  
Methylation Patterns ◽  
Histone Methylation And Acetylation

The aberrant DNA methylation of promoter regions of housekeeping genes leads to gene silencing. Additional epigenetic events, such as histone methylation and acetylation, also play a very important role in the definitive repression of gene expression by DNA methylation. If the aberrant DNA methylation of promoter regions is the starting or the secondary event leading to the gene silencing is still debated. Mechanisms controlling DNA methylation patterns do exist although they have not been ultimately proven. Our data suggest that poly(ADP-ribosyl)ation might be part of this control mechanism. Thus an additional epigenetic modification seems to be involved in maintaining tissue and cell-type methylation patterns that when formed during embryo development, have to be rigorously conserved in adult organisms.Key words: DNA methylation, chromatin, poly(ADP-ribosyl)ation.

Transcriptional reprogramming and ultrastructure during atrophy and recovery of mouse soleus muscle

2004 ◽  
Vol 20 (1) ◽  
pp. 97-107 ◽  
Author(s):  
Christoph Däpp ◽  
Silvia Schmutz ◽  
Hans Hoppeler ◽  
Martin Flück
Keyword(s):  
Soleus Muscle ◽  
Glycolytic Enzyme ◽  
Hindlimb Suspension ◽  
Published Data ◽  
Capillary Length ◽  
Muscle Plasticity ◽  
Fiber Area ◽  
Transcriptional Reprogramming ◽  
Myogenic Factors ◽  
Species Specific

This study investigated the use of the hindlimb suspension (HS) and reloading model of mice for the mapping of ultrastructural and gene expressional alterations underlying load-dependent muscular adaptations. Mice were hindlimb suspended for 7 days or kept as controls ( n = 12). Soleus muscles were harvested after HS (HS7, n = 23) or after resuming ambulatory cage activity (reloading) for either 1 day (R1, n = 13) or 7 days (R7, n = 9). Using electron microscopy, a reduction in mean fiber area (−37%) and in capillary-to-fiber ratio (from 1.83 to 1.42) was found for HS7. Subsequent reloading caused an increase in interstitial cells (+96%) and in total capillary length (+57%), whereas mean fiber area and capillary-to-fiber ratio did not significantly change compared with HS. Total RNA in the soleus muscle was altered with both HS (−63%) and reloading (+108% in R7 compared with control). This is seen as an important adaptive mechanism. Gene expression alterations were assessed by a muscle-specific low-density cDNA microarray. The transcriptional adjustments indicate an early increase of myogenic factors during reloading together with an overshoot of contractile (MyHC I and IIa) and metabolic (glycolytic and oxidative) mRNA amounts and suggest mechano-sensitivity of factors keeping the sarcomeres in register (desmin, titin, integrin-β1). Important differences to published data from former rat studies were found with the mouse HS model for contractile and glycolytic enzyme expression. These species-specific differences need to be considered when transgenic mice are used for the elucidation of monogenetic factors in mechano-dependent muscle plasticity.

scholarly journals Satellite cell content is specifically reduced in type II skeletal muscle fibers in the elderly

2007 ◽  
Vol 292 (1) ◽  
pp. E151-E157 ◽  
Author(s):  
Lex B. Verdijk ◽  
René Koopman ◽  
Gert Schaart ◽  
Kenneth Meijer ◽  
Hans H. C. M. Savelberg ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Fiber Type ◽  
The Elderly ◽  
Type I ◽  
Type Ii ◽  
Fiber Area ◽  
Muscle Fiber Atrophy ◽  
Fiber Atrophy ◽  
Type Ii Fibers

Satellite cells (SC) are essential for skeletal muscle growth and repair. Because sarcopenia is associated with type II muscle fiber atrophy, we hypothesized that SC content is specifically reduced in the type II fibers in the elderly. A total of eight elderly (E; 76 ± 1 yr) and eight young (Y; 20 ± 1 yr) healthy males were selected. Muscle biopsies were collected from the vastus lateralis in both legs. ATPase staining and a pax7-antibody were used to determine fiber type-specific SC content (i.e., pax7-positive SC) on serial muscle cross sections. In contrast to the type I fibers, the proportion and mean cross-sectional area of the type II fibers were substantially reduced in E vs. Y. The number of SC per type I fiber was similar in E and Y. However, the number of SC per type II fiber was substantially lower in E vs. Y (0.044 ± 0.003 vs. 0.080 ± 0.007; P < 0.01). In addition, in the type II fibers, the number of SC relative to the total number of nuclei and the number of SC per fiber area were also significantly lower in E. This study is the first to show type II fiber atrophy in the elderly to be associated with a fiber type-specific decline in SC content. The latter is evident when SC content is expressed per fiber or per fiber area. The decline in SC content might be an important factor in the etiology of type II muscle fiber atrophy, which accompanies the loss of skeletal muscle with aging.

scholarly journals Nutritional Support and Prophylaxis of Azithromycin for Pregnant Women to Improve Birth Outcomes in Peri-Urban Slums of Karachi, Pakistan – A Protocol of Multi-arm Assessor Blinded Randomized Controlled Trial (Mumta PW Trial)

2021 ◽  
Author(s):  
Ameer Muhammad ◽  
Zoha Zahid Fazal ◽  
Benazir Baloch ◽  
Imran Nisar ◽  
Fyezah Jehan ◽  
...  
Keyword(s):  
Informed Consent ◽  
Pregnant Women ◽  
Low Income ◽  
Controlled Trial ◽  
Perinatal Outcomes ◽  
Urban Slum ◽  
Control Group ◽  
Maternal Undernutrition ◽  
Randomized Controlled ◽  
Group 2

Abstract BackgroundMaternal undernutrition is critical in the etiology of poor perinatal outcomes and accounts for 20% of small-for-gestational-age (SGA) births. High levels of food insecurity, antenatal undernourishment and childhood undernutrition necessitate the supplementation of fortified balanced energy-protein (BEP) during pregnancy in low-income settings especially with scarce literature available in this subject. Hence, this paper extensively covers the protocol of such a trial conducted in an urban slum of Karachi, Pakistan. Methods The trial is community-based, open-labelled, four-arm, and randomized controlled that will include parallel group assignments with a 1:1:1:1 allocation ratio in low-income squatter settlements in urban Karachi, Pakistan. All pregnant women (PW), if identified between > 8 and <19 weeks of gestation based on ultrasound, will be offered routine antenatal care (ANC) counseling and voluntary participation in the trial after written informed consent. A total number of 1836 PW will be enrolled with informed consent and randomly allocated to one of the four arms receiving: (1) ANC counseling only (control group), (2) ANC counseling plus BEP supplement (intervention arm 1), (3) ANC counseling plus BEP supplement plus 2 doses Azithromycin (intervention arm 2), or (4) ANC counseling plus BEP supplement plus daily single dose of Nicotinamide and Choline (intervention arm 3). Trial Registration ClinicalTrials.gov NCT04012177. Registered on July 9, 2019. (https://clinicaltrials.gov/ct2/show/NCT04012177)

scholarly journals Rbfox1 is required for myofibril development and maintaining fiber-type specific isoform expression in Drosophila muscles

2021 ◽  
Author(s):  
Elena Nikonova ◽  
Ketaki Kamble ◽  
Amartya Mukherjee ◽  
Christiane Barz ◽  
Upendra Nongthomba ◽  
...  
Keyword(s):  
Muscle Development ◽  
Rna Binding ◽  
Troponin I ◽  
Rna Binding Proteins ◽  
Fiber Type ◽  
Specific Gene ◽  
Fiber Types ◽  
Transcript Levels ◽  
Splice Isoform ◽  
Isoform Expression

Protein isoform transitions confer distinct properties on muscle fibers and are regulated predominantly by differential transcription and alternative splicing. RNA-binding Fox protein 1 (Rbfox1) can affect both transcript levels and splicing, and is known to control skeletal muscle function. However, the detailed mechanisms by which Rbfox1 contributes to normal muscle development and physiology remain obscure. In this study, we report that Rbfox1 contributes to the generation of adult muscle diversity in Drosophila. Rbfox1 is differentially expressed in tubular and fibrillar muscle fiber types. RNAi knockdown of Rbfox1 leads to a loss of flight, climbing and jumping ability, as well as eclosion defects. Myofibers in knockdown muscle are frequently torn, and sarcomeres are hypercontracted. These defects arise from mis-regulation of fiber-type specific gene and splice isoform expression, notably loss of an IFM-specific isoform of Troponin-I that is critical for regulating myosin activity. We find that Rbfox1 influences mRNA transcript levels through 1) direct binding of 3'-UTRs of target transcripts as well as 2) through regulation of myogenic transcription factors, including Mef2, Exd and Salm. Moreover, Rbfox1 modulates splice isoform expression through 1) direct regulation of target splice events in structural genes and 2) regulation of the CELF-family RNA-binding protein Bruno1. Our data indicate that cross-regulatory interactions observed between FOX and CELF family RNA-binding proteins in vertebrates are conserved between their counterparts, Rbfox1 and Bruno1 in flies. Rbfox1 thus affects muscle development by regulation of both fiber-type specific gene and gene isoform expression dynamics of identity genes and structural proteins.

scholarly journals Chronic Polyhydramnios: A Medical Entity Which Could Be a Model of Muscle Development in Decreased Mechanical Loading Condition

2022 ◽  
Vol 12 ◽  
Author(s):  
Slobodan Sekulić ◽  
Branislava Jakovljević ◽  
Darinka Korovljev ◽  
Svetlana Simić ◽  
Ivan Čapo ◽  
...  
Keyword(s):  
Mechanical Loading ◽  
Muscle Development ◽  
Fiber Type ◽  
Published Data ◽  
Type I ◽  
Muscle Disorders ◽  
Physical Loading ◽  
Extensor Muscles ◽  
Medical Entity

Polyhydramnios is a condition related to an excessive accumulation of amniotic fluid in the third trimester of pregnancy and it can be acute and chronic depending on the duration. Published data suggest that during muscle development, in the stage of late histochemical differentiation decreased mechanical loading cause decreased expression of myosin heavy chain (MHC) type 1 leading to slow-to-fast transition. In the case of chronic polyhydramnios, histochemical muscle differentiation could be affected as a consequence of permanent decreased physical loading. Most affected would be muscles which are the most active i.e., spine extensor muscles and muscles of legs. Long-lasting decreased mechanical loading on muscle should cause decreased expression of MHC type 1 leading to slow-to-fast transition, decreased number of muscle fiber type I especially in extensor muscles of spine and legs. Additionally, because MHC type 1 is present in all skeletal muscles it could lead to various degrees of hypotrophy depending on constituting a percentage of MHC type 1 in affected muscles. These changes in the case of preexisting muscle disorders have the potential to deteriorate the muscle condition additionally. Given these facts, idiopathic chronic polyhydramnios is a rare opportunity to study the influence of reduced physical loading on muscle development in the human fetus. Also, it could be a medical entity to examine the influence of micro- and hypogravity conditions on the development of the fetal muscular system during the last trimester of gestation.

scholarly journals DNA methylation presents distinct binding sites for human transcription factors

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Shaohui Hu ◽  
Jun Wan ◽  
Yijing Su ◽  
Qifeng Song ◽  
Yaxue Zeng ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Epigenetic Modification ◽  
Specific Binding ◽  
Protein Microarray ◽  
Embryonic Stem ◽  
Underlying Mechanism ◽  
Binding Activity ◽  
Site Directed Mutagenesis ◽  
Promoter Regions

DNA methylation, especially CpG methylation at promoter regions, has been generally considered as a potent epigenetic modification that prohibits transcription factor (TF) recruitment, resulting in transcription suppression. Here, we used a protein microarray-based approach to systematically survey the entire human TF family and found numerous purified TFs with methylated CpG (mCpG)-dependent DNA-binding activities. Interestingly, some TFs exhibit specific binding activity to methylated and unmethylated DNA motifs of distinct sequences. To elucidate the underlying mechanism, we focused on Kruppel-like factor 4 (KLF4), and decoupled its mCpG- and CpG-binding activities via site-directed mutagenesis. Furthermore, KLF4 binds specific methylated or unmethylated motifs in human embryonic stem cells in vivo. Our study suggests that mCpG-dependent TF binding activity is a widespread phenomenon and provides a new framework to understand the role and mechanism of TFs in epigenetic regulation of gene transcription.

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