Fetal Muscle Research Articles

Integrated Bioinformatics Analysis Reveals Potential Pathway Biomarkers and Their Interactions for Clubfoot

BackgroundCongenital talipes equinovarus (clubfoot), one of the most regular pediatric congenital skeletal anomalies, seriously affects the normal growth and development of about 1 in 1000 newborns. Although it has been investigated widely, the etiology and pathogenesis of clubfoot are still controversial.Material/Methodsg: Profiler, NetworkAnalyst and WebGestalt were used to probe the enriched signaling pathways by using the Gene Ontology (GO), Human Phenotype Ontology (HP), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome (REAC), and WikiPathways (WP) databases. Large numbers of enriched signaling pathways were identified using the integrated bioinformatics enrichment analyses.ResultsApoptosis or programmed cell death (PCD), disease, muscle contraction, metabolism, and immune system were the top functions. Embryo or organ morphogenesis and development, cell or muscle contraction, and apoptosis were the top biological processes, and cell/muscle contraction and apoptosis were the top molecular functions using enriched GO terms analysis. There were a large number of complex interactions in the genes, enriched pathways, and transcription factor (TF)-miRNA co-regulatory networks. Transcription factors such as FOXN3, GLI3, HOX, and NCOR2 family regulated the gene expression of APAF1, BCL2, BID, CASP, MTHFR, and TPM family.ConclusionsThe results of bioinformatics enrichment analysis not only supported the previously proposed hypotheses, e.g., extracellular matrix (ECM) abnormality, fetal movement reducing, genetic abnormality, muscle abnormality, neurological abnormality, skeletal abnormality and vascular abnormality, but also indicated that cellular or immune responses to external stimulus, molecular transport and metabolism may be new etiological mechanisms in clubfoot.

Maternal undernutrition affects secondary myogenesis in a muscle-dependent way across the major muscles of 70-day old ovine fetuses

Abstract The present study evaluated the effects of maternal undernutrition induced by a lower natural pasture allowance from 23 days before conception on the distribution and morphometry of muscle precursor cells and the expression of PCNA, Myogenin and Pax 7 in muscles Psoas major, Longissimus lumborum, Semitendinosus, Semimembranosus, Gluteobiceps and Gluteus medius of 70-day old sheep fetuses. Ewes were assigned to two nutritional treatments (complete randomized block design) beginning 23 days before conception: High pasture allowance (HPA) ewes grazed on natural grasslands at 10−12 kg dry matter (DM) /100 kg of live weight (LW)/day, while low pasture allowance (LPA) ewes grazed at 5−8 kg DM /100 kg of LW/day. On day 70 of pregnancy 18 ewes (nine/treatment) carrying single male fetuses were euthanized and samples were taken from fetal muscles. Samples were stained with hematoxylin-eosin to evaluate muscle morphology and treated with immunohistochemical methods to evaluate the expression of myogenic regulatory factors. Maternal undernutrition reduced the ratio of secondary to primary fibers (P

Prediction of the Secretome and the Surfaceome: A Strategy to Decipher the Crosstalk between Adipose Tissue and Muscle during Fetal Growth.

Crosstalk between adipose and muscular tissues is hypothesized to regulate the number of muscular and adipose cells during fetal growth, with post-natal consequences on lean and fat masses. Such crosstalk largely remains, however, to be described. We hypothesized that a characterization of the proteomes of adipose and muscular tissues from bovine fetuses may enhance the understanding of the crosstalk between these tissues through the prediction of their secretomes and surfaceomes. Proteomic experiments have identified 751 and 514 proteins in fetal adipose tissue and muscle. These are mainly involved in the regulation of cell proliferation or differentiation, but also in pathways such as apoptosis, Wnt signalling, or cytokine-mediated signalling. Of the identified proteins, 51 adipokines, 11 myokines, and 37 adipomyokines were predicted, together with 26 adipose and 13 muscular cell surface proteins. Analysis of protein–protein interactions suggested 13 links between secreted and cell surface proteins that may contribute to the adipose–muscular crosstalk. Of these, an interaction between the adipokine plasminogen and the muscular cell surface alpha-enolase may regulate the fetal myogenesis. The in silico secretome and surfaceome analyzed herein exemplify a powerful strategy to enhance the elucidation of the crosstalk between cell types or tissues.

Exercise Intergenerationally Drives Muscle-Based Thermogenesis and Myogenesis in Offspring Impaired Due to Maternal Obesity

Abstract Objectives Maternal obesity (MO) predisposes metabolic dysfunction in offspring muscle. Skeletal muscle-dependent non-shivering thermogenesis (NST) is emerging as a critical mechanism for maintaining energy homeostasis, but the effects of maternal exercise on muscle-based thermogenesis in offspring remains unexplored. In addition, the impact of maternal obesity and exercise on fetal muscle development is unclear, which will also be examined. The objective of the current study is to explore the effects of maternal exercise on muscle-based thermogenesis and myogenesis in fetuses impaired due to MO. Methods Female C57BL/6 J mice were randomized and assigned to either control (CON, 10 kcal% from fat) or obesogenic diet (OB, 60 kcal% from fat) for 8 weeks to induce obesity and then mated. Then, pregnant mice in obesogenic diet were further separated into two groups with/without exercise (daily 60 min exercise) during pregnancy, which resulted in three treatments: control (CON), OB, and OB-EX (n = 6 per group). Fetal skeletal muscles were collected at embryonic day 18.5 (E18.5). In another cohort of animals, maternal mice were allowed to give birth and surface temperature of neonates was measured. Statistical analysis were conducted using one way analysis of variance (ANOVA); a pregnancy/litter was considered as an experimental unit. Results OB reduced surface temperature of neonates (P < 0.01). In E18.5 fetal muscle, OB downregulated muscle-based thermogenic gene expression (P < 0.05), including Sln, Serca2, and Ryr1. In addition, the expression of mitochondriogenic genes (P < 0.05), including Ppargc1a and Tfam, was also reduced in OB fetal female and male muscle. These adverse changes were prevented due to exercise during pregnancy. Furthermore, maternal exercise protected against the downregulation of myogenesis-related gene expression, including MyoD, Myogenin, Myf5, and Pax7, due to MO. Conclusions Exercise during pregnancy enhanced muscle-based thermogenic gene expression and myogenesis which were impaired due to MO, suggesting that maternal exercise intergenerationally improves metabolic health of offspring. Funding Sources Supported by NIH Grant R01HD067449.

A Novel Mechanism of bta-miR-210 in Bovine Early Intramuscular Adipogenesis.

Intramuscular fat (IMF) is one of the major factors determining beef quality. IMF formation is influenced by multiple conditions including genetic background, age and nutrition. In our previous investigation, bta-miR-210 was found to be increased during adipogenesis using miRNA-seq. In this study, we validated the upregulation of bta-miR-210 in platelet-derived growth factor receptor α positive (PDGFRα+) progenitor cells during adipogenic differentiation in vitro. To investigate its role in adipogenesis, bta-miR-210 mimics were introduced into progenitor cells, which resulted in enhanced intracellular lipid accumulation. Accordingly, the expression of adipocyte-specific genes significantly increased in the bta-miR-210 mimic group compared to that in the negative control group (p < 0.01). Dual-luciferase reporter assays revealed that WISP2 is a target of bta-miR-210. WISP2 knockdown enhanced adipogenesis. In conclusion, bta-miR-210 positively regulates the adipogenesis of PDGFRα+ cells derived from bovine fetal muscle by targeting WISP2.

Maternal Obesity and Western-Style Diet Impair Fetal and Juvenile Offspring Skeletal Muscle Insulin-Stimulated Glucose Transport in Nonhuman Primates.

Infants born to mothers with obesity have a greater risk for childhood obesity and metabolic diseases; however, the underlying biological mechanisms remain poorly understood. We used a Japanese macaque model to investigate whether maternal obesity combined with a Western-style diet (WSD) impairs offspring muscle insulin action. Adult females were fed a control or WSD prior to and during pregnancy through lactation, and offspring subsequently weaned to a control or WSD. Muscle glucose uptake and signaling were measured ex vivo in fetal (n = 5-8/group) and juvenile (n = 8/group) offspring. In vivo signaling was evaluated after an insulin bolus just prior to weaning (n = 4-5/group). Maternal WSD reduced insulin-stimulated glucose uptake and impaired insulin signaling at the level of Akt phosphorylation in fetal muscle. In juvenile offspring, insulin-stimulated glucose uptake was similarly reduced by both maternal and postweaning WSD and corresponded to modest reductions in insulin-stimulated Akt phosphorylation relative to controls. We conclude that maternal WSD leads to a persistent decrease in offspring muscle insulin-stimulated glucose uptake even in the absence of increased offspring adiposity or markers of systemic insulin resistance. Switching offspring to a healthy diet did not reverse the effects of maternal WSD on muscle insulin action, suggesting earlier interventions may be warranted.

Analysis of DNA methylation profiles during sheep skeletal muscle development using whole-genome bisulfite sequencing

BackgroundDNA methylation is an epigenetic regulatory form that plays an important role in regulating the gene expression and the tissues development.. However, DNA methylation regulators involved in sheep muscle development remain unclear. To explore the functional importance of genome-scale DNA methylation during sheep muscle growth, this study systematically investigated the genome-wide DNA methylation profiles at key stages of Hu sheep developmental (fetus and adult) using deep whole-genome bisulfite sequencing (WGBS).ResultsOur study found that the expression levels of DNA methyltransferase (DNMT)-related genes were lower in fetal muscle than in the muscle of adults. The methylation levels in the CG context were higher than those in the CHG and CHH contexts, and methylation levels were highest in introns, followed by exons and downstream regions. Subsequently, we identified 48,491, 17, and 135 differentially methylated regions (DMRs) in the CG, CHG, and CHH sequence contexts and 11,522 differentially methylated genes (DMGs). The results of bisulfite sequencing PCR (BSP) correlated well with the WGBS-Seq data. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation analysis revealed that some DMGs were involved in regulating skeletal muscle development and fatty acid metabolism. By combining the WGBS-Seq and previous RNA-Seq data, a total of 159 overlap genes were obtained between differentially expressed genes (DEGs) and DMGs (FPKM > 10 and fold change > 4). Finally, we found that 9 DMGs were likely to be involved in muscle growth and metabolism of Hu sheep.ConclusionsWe systemically studied the global DNA methylation patterns of fetal and adult muscle development in Hu sheep, which provided new insights into a better understanding of the epigenetic regulation of sheep muscle development.

Maternal exercise programs skeletal muscle metabolic dysfunction in offspring mice challenged with high fat diet.

Exercise, including maternal exercise becomes increasingly less common. Though improper maternal nutrition and obesity are known to affect fetal muscle development and predisposes offspring to metabolic dysfunction, the effects of maternal exercise (ME) on fetal muscle development and offspring metabolic health are largely undefined.PURPOSETo investigate the effects of maternal exercise on mitochondrial biogenesis during fetal muscle development, and muscle function and metabolic health in offspring following high fat diet (HFD) challenge.METHODSFemale C57BL/6J mice were randomized and assigned into a control (CON) or an exercise (EX) group (n = 6 per group) fed a normal chow. Exercise was performed every morning for 60 min during pregnancy. Then, the animals were mated, and the skeletal muscle samples were collected at embryonic day 18.5, weaning, and after 8 weeks of high fat diet (HFD; 60 kcal% from fat) challenge in both females and males. Statistical analysis were conducted using student’s t‐test and/or one/two way analysis of variance (ANOVA).RESULTSME muscle fiber diameters and enhanced muscle endurance capacity in offspring (P &lt; 0.05), which were positively associated with switching muscle fibers from type IIb/x to type I and IIa and mitochondrial biogenesis (P &lt; 0.05), but negatively correlated with atrophy‐related Atrogin‐1 and Murf1 gene expression (P &lt; 0.05). Mechanistically, ME enhanced DNA demethylation of Pgc‐1a promoter and its expression during fetal muscle development. Importantly, such changes in DNA methylation maintained in offspring muscle before and after HFD challenge, resulting in elevated Pgc‐1a mRNA expression and increased contents of PGC‐1a1 and 4 isoforms, which improved metabolic health.CONCLUSIONSThis study identifies that ME enhances DNA demethylation of the Pgc‐1a promoter during fetal muscle development, which has programming effects on the exercise endurance capacity and metabolic health of muscle in offspring.Support or Funding InformationThis work was supported by National Institutes of Health Grants R01‐HD067449.Maternal exercise (ME) enhances adaptation to endurance training of offspring mice (A,B) and the proportion of muscle type I fiber composition before and following HFD challenge (C). ME decreases muscle atrophy‐related genes following HFD challenge (D,E). Data are mean ± s.e.m. and each dot represents one litter.; two‐sided P values by unpaired Student’s t‐test (D,E) or two‐way repeated measures ANOVA followed by Tukey’s test (B).Figure 1

Development and thyroid hormone dependence of skeletal muscle mitochondrial function towards birth.

Key points Skeletal muscle energy requirements increase at birth but little is known regarding the development of mitochondria that provide most of the cellular energy as ATP.Thyroid hormones are known regulators of adult metabolism and are important in driving several aspects of fetal development, including muscle fibre differentiation.Mitochondrial density and the abundance of mitochondrial membrane proteins in skeletal muscle increased during late gestation. However, mitochondrial functional capacity, measured as oxygen consumption rate, increased primarily after birth.Fetal hypothyroidism resulted in significant reductions in mitochondrial function and density in skeletal muscle before birth.Mitochondrial function matures towards birth and is dependent on the presence of thyroid hormones, with potential implications for the health of pre‐term and hypothyroid infants. Birth is a significant metabolic challenge with exposure to a pro‐oxidant environment and the increased energy demands for neonatal survival. This study investigated the development of mitochondrial density and activity in ovine biceps femoris skeletal muscle during the perinatal period and examined the role of thyroid hormones in these processes. Muscle capacity for oxidative phosphorylation increased primarily after birth but was accompanied by prepartum increases in mitochondrial density and the abundance of electron transfer system (ETS) complexes I–IV and ATP‐synthase as well as by neonatal upregulation of uncoupling proteins. This temporal disparity between prepartum maturation and neonatal upregulation of mitochondrial oxidative capacity may protect against oxidative stress associated with birth while ensuring energy availability to the neonate. Fetal thyroid hormone deficiency reduced oxidative phosphorylation and prevented the prepartum upregulation of mitochondrial density and ETS proteins in fetal skeletal muscle. Overall, the data show that mitochondrial function matures over the perinatal period and is dependent on thyroid hormones, with potential consequences for neonatal viability and adult metabolic health.

Primary Progenitor Muscle Cells for Regenerative Medicine: Standardization of Therapeutic Protocols and Optimized In Vivo Murine Model For Volumetric Muscle Loss

Skeletal muscle tissue engineering constitutes an emerging therapeutic repair strategy aiming for structural and functional restoration following traumatic injury, deep burns, congenital malformation or surgical tumor removal. As for similar musculoskeletal acute and degenerative affections, allogenic progenitor cell therapy represents a promising clinical approach to synergistically supplement traditional surgical care. Preliminary studies have established the adequation of primary human fetal muscle progenitors (hFMPs) for applications in regenerative medicine. Such therapeutic cell sources combined with bioresorbable scaffolds optimally integrate in murine muscle injury models without causing immune rejection. The present work aimed at functional recovery assessment following standardized application of hFMPs in an optimized murine skeletal muscle wound model. Cryopreserved hFMPs were initiated and culture-expanded before seeding in equine collagen scaffolds. Gastrocnemius muscles of C57BL/6 mice were injured following a standardized protocol.

TRIP6 accelerates the proliferation and migration of fetal airway smooth muscle cells by enhancing YAP activation

The thyroid receptor interactor protein 6 (TRIP6) has emerged as a key regulator for the proliferation and migration of various cells. However, whether TRIP6 is involved in regulating the proliferation and migration of airway smooth muscle (ASM) cells in the progression of pediatric asthma remains undetermined. The present study investigated the function of TRIP6 in regulating the proliferation and migration of fetal ASM cells induced by tumor necrosis factor (TNF)-α in vitro. The results revealed that TRIP6 expression was significantly upregulated in TNF-α-stimulated ASM cells. Loss-of-function experiments demonstrated that the knockdown of TRIP6 markedly suppressed TNF-α-proliferation and migration of ASM cells. By contrast, overexpression of TRIP6 had the opposite effect. In-depth research uncovered that TNF-α stimulation promoted the activation of yes-associated protein (YAP), which could be significantly reversed by TRIP6 silencing. Moreover, inactivation of YAP significantly reversed the promotion effect of TRIP6 overexpression on TNF-α-induced ASM cell proliferation and migration. Overall, these results reveal that upregulation of TRIP6 contributes to the proliferation and migration of fetal ASM cells by enhancing YAP activation, highlighting the importance of the TRIP6/YAP axis in the airway remodeling of pediatric asthma.

Fetal ovine skeletal and cardiac muscle transcriptomics are differentially altered by increased maternal cortisol during gestation.

We have previously found that in utero exposure to excess maternal cortisol (1 mg/kg/day) in late gestation increases the incidence of stillbirth during labor and produces fetal bradycardia at birth. In the interventricular septum, mitochondrial DNA (mt-DNA) was decreased, and transcriptomics and metabolomics were consistent with altered mitochondrial metabolism. The present study uses transcriptomics to model effects of increased maternal cortisol on fetal biceps femoris. Transcriptomic modeling revealed that pathways related to mitochondrial metabolism were downregulated, whereas pathways for regulation of reactive oxygen species and activation of the apoptotic cascade were upregulated. Mt-DNA and the protein levels of cytochrome C were significantly decreased in the biceps femoris. RT-PCR validation of the pathways confirmed a significant decrease in SLC2A4 mRNA levels and a significant increase in PDK4, TXNIP, ANGPTL4 mRNA levels, suggesting that insulin sensitivity of the biceps femoris muscle may be reduced in cortisol offspring. We also tested for changes in gene expression in diaphragm by rt-PCR. PDK4, TXNIP, and ANGPTL4 mRNA were also increased in the diaphragm, but SLC2A4, cytochrome C protein, and mt-DNA were unchanged. Comparison of the change in gene expression in biceps femoris to that in cardiac interventricular septum and left ventricle showed few common genes and little overlap in specific metabolic or signaling pathways, despite reduction in mt-DNA in both heart and biceps femoris. Our results suggest that glucocorticoid exposure alters expression of nuclear genes important to mitochondrial activity and oxidative stress in both cardiac and skeletal muscle tissues, but that these effects are tissue-specific.

Effect of maternal nutrient restriction on skeletal muscle mass and associated molecular pathways in SGA and Non-SGA sheep fetuses

Maternal nutrient restriction causes small for gestational age (SGA) offspring, which exhibit a higher risk for metabolic syndrome in adulthood. Fetal skeletal muscle is particularly sensitive to maternal nutrient restriction, which impairs muscle mass and metabolism. Using a 50% nutrient restriction treatment from gestational day (GD) 35 to GD 135 in sheep, we routinely observe a spectral phenotype of fetal weights within the nutrient-restricted (NR) group. Thus, our objective was to evaluate the effect of maternal NR on muscle mass, myofiber hypertrophy, myonuclear dotation, and molecular markers for protein synthesis and degradation, while accounting for the observed fetal weight variation. Within the NR group, we classified upper-quartile fetuses into NR(Non-SGA) (n = 11) and lower-quartile fetuses into NR(SGA) (n = 11). A control group (n = 12) received 100% of nutrient requirements throughout pregnancy. At GD 135, fetal plasma and organs were collected, and gastrocnemius and soleus muscles were sampled for investigation. Results showed decreased (P < 0.05) absolute tissue/organ weights, including soleus and gastrocnemius muscles, in NR(SGA) fetuses compared to NR(Non-SGA) and control. Myofiber cross-sectional area was smaller in NR(SGA) vs control for gastrocnemius (P = 0.0092) and soleus (P = 0.0097) muscles. Within the gastrocnemius muscle, the number of myonuclei per myofiber was reduced (P = 0.0442) in NR(SGA) compared to control. Cortisol may induce protein degradation. However, there were no differences in fetal cortisol among groups. Nevertheless, for gastrocnemius muscle, cortisol receptor (NR3C1; P = 0.0124), and FOXO1 (P = 0.0131) were upregulated in NR(SGA) compared to control while NR(Non-SGA) did not differ from the other 2 groups. KLF15 was upregulated (P = 0.0002) in both NR(SGA) and NR(Non-SGA); while FBXO32, TRIM63, BCAT2 or MSTN did not differ. For soleus muscle, KLF15 mRNA was upregulated (P = 0.0145) in NR(SGA) compared to control, and expression of MSTN was increased (P = 0.0259) in NR(SGA) and NR(Non-SGA) compared to control. At the protein level, none of the mentioned molecules nor total ubiquitin-labeled proteins differed among groups (P > 0.05). Indicators of protein synthesis (total and phosphorylated MTOR, EI4EBP1, and RPS6KB1) did not differ among groups in either muscle (P > 0.05). Collectively, results highlight that maternal NR unequally affects muscle mass in NR(SGA) and NR(Non-SGA) fetuses, and alterations in myofiber cross-sectional area and myonuclei number partially explain those differences.

Reduced Na+ K+ -ATPase activity may reduce amino acid uptake in intrauterine growth restricted fetal sheep muscle despite unchanged ex vivo amino acid transporter activity.

Fetuses with intrauterine growth restriction (IUGR) have reduced muscle mass that persists postnatally, which may contribute to their increased risk for adult onset metabolic diseases, such as diabetes and obesity. Amino acid transporter-mediated histidine uptake and system L amino acid transporter activity were similar in sarcolemmal membranes isolated from control and IUGR hindlimb skeletal muscle. Activity of Na+ K+ -ATPase, which is responsible for establishing the sodium gradient necessary for system A and N amino acid transporter function, was significantly reduced in IUGR skeletal muscle sarcolemma compared to control. ATP content was lower in IUGR skeletal muscle. Expression and phosphorylation of proteins in the mechanistic target of rapamycin pathway were similar in control and IUGR skeletal muscle homogenate. Our data suggest that lower Na+ K+ -ATPase activity, which reduces the driving force for active amino acid transport, and lower ATP availability contribute to reduced amino acid uptake and protein synthesis in IUGR fetal skeletal muscle. Fetuses with intrauterine growth restriction (IUGR) have lower muscle mass that persists postnatally. Using a sheep model of placental insufficiency and IUGR, we have previously demonstrated lower net total uptake of amino acids by the fetal hindlimb and lower skeletal muscle protein synthesis rates. To investigate the mechanisms underlying these changes, we tested the hypothesis that ex vivo amino acid transporter and Na+ K+ -ATPase activity is reduced, and ex vivo ATP levels are lower in hindlimb skeletal muscle of the IUGR fetus. We developed a novel protocol to measure transporter-mediated histidine uptake, system L amino acid transporter activity and Na+ K+ -ATPase activity using sarcolemmal membranes isolated from hindlimb muscle of control (CON, n=11-12) and IUGR (n=12) late gestation fetal sheep. We also determined ATP content and the activity of insulin and mechanistic target of rapamycin (mTOR) signalling, which are involved in regulating cellular amino acid uptake and protein synthesis, by measuring the expression and phosphorylation of AKT, 4E-BP1, eIF2α, AMPKα, p70 S6 kinase and rpS6 in muscle homogenates. Transporter-mediated histidine uptake and system L activity were similar in control and IUGR sarcolemma, although ex vivo Na+ K+ -ATPase activity was lower by 64% (P=0.019) in IUGR sarcolemma. ATP content was lower by 25% (P=0.007) in IUGR muscle. Insulin, AMPK, and mTOR signalling activity was similar in control and IUGR muscle. We speculate that reduced muscle sarcolemmal Na+ K+ -ATPase activity and lower ATP content diminishes the sodium gradient in vivo, resulting in a reduced driving force for sodium-dependent transporters and subsequently lower muscle amino acid uptake.

Impact of genotype, body weight and sex on the prenatal muscle transcriptome of Iberian pigs.

Growth is dependent on genotype and diet, even at early developmental stages. In this study, we investigated the effects of genotype, sex, and body weight on the fetal muscle transcriptome of purebred Iberian and crossbred Iberian x Large White pigs sharing the same uterine environment. RNA sequencing was performed on 16 purebred and crossbred fetuses with high body weight (340±14g and 415±14g, respectively) and 16 with low body weight (246±14g and 311±14g, respectively), on gestational day 77. Genotype had the greatest effect on gene expression, with 645 genes identified as differentially expressed (DE) between purebred and crossbred animals. Functional analysis showed differential regulation of pathways involved in energy and lipid metabolism, muscle development, and tissue disorders. In purebred animals, fetal body weight was associated with 35 DE genes involved in development, lipid metabolism and adipogenesis. In crossbred animals, fetal body weight was associated with 60 DE genes involved in muscle development, viability, and immunity. Interestingly, the results suggested an interaction genotype*weight for some DE genes. Fetal sex had only a modest effect on gene expression. This study allowed the identification of genes, metabolic pathways, biological functions and regulators related to fetal genotype, weight and sex, in animals sharing the same uterine environment. Our findings contribute to a better understanding of the molecular events that influence prenatal muscle development and highlight the complex interactions affecting transcriptional regulation during development.

Human fetal mesoangioblasts reveal tissue-dependent transcriptional signatures.

Mesoangioblasts (MABs) derived from adult skeletal muscles are well‐studied adult stem/progenitor cells that already entered clinical trials for muscle regeneration in genetic diseases; however, the transcriptional identity of human fetal MABs (fMABs) remains largely unknown. Herein we analyzed the transcriptome of MABs isolated according to canonical markers from fetal atrium, ventricle, aorta, and skeletal muscles (from 9.5 to 13 weeks of age) to uncover specific gene signatures correlating with their peculiar myogenic differentiation properties inherent to their tissue of origin. RNA‐seq analysis revealed for the first time that human MABs from fetal aorta, cardiac (atrial and ventricular), and skeletal muscles display subsets of differentially expressed genes likely representing distinct expression signatures indicative of their original tissue. Identified GO biological processes and KEGG pathways likely account for their distinct differentiation outcomes and provide a set of critical genes possibly predicting future specific differentiation outcomes. This study reveals novel information regarding the potential of human fMABs that may help to improve specific differentiation outcomes relevant for therapeutic muscle regeneration.

Morphometric study and occurrence of the palmaris longus muscle in human fetuses

Morphometric study and occurrence of the palmaris longus muscle in human fetuses

BMP4 and Rosiglitazone Improves Adipogenesis of Bovine Fetal Muscle Derived Progenitor Cells

BMP4 and Rosiglitazone Improves Adipogenesis of Bovine Fetal Muscle Derived Progenitor Cells

Bovine fetal tissue extracts as an alternative to fetal serum for in vitro reproduction of viruses

The authors assessed the possibility of substitution of the serum component with tissue extracts (muscles, liver, kidneys) of bovine fetuses in the culture medium during the cultivation of transplanted LEK and Vero cell lines, as well as the reproduction of infectious rhinotracheitis IR, PI-3 viruses and reovirus on them. The greatest stimulating effect on LEK and Vero cells was obtained from bovine fetuses muscle extract. The effect of this extract on the proliferative activity of LEK and Vero cells is significant and amounts to 27 and 25%, respectively. The power of the effect of liver and kidney extracts is significantly lower and equal, respectively, 15 and 18% for LEK and 14 and 19% for Vero, although it is reliable. The reproductive activity of IR and PI-3 viruses when using tissue extracts was inferior to that when using blood serum. The stimulating effect of blood serum and muscle extract on the reproduction of reovirus was comparable. The effect of fetal muscle extract on the reproduction of IR, PI-3 viruses and reovirus is reliable and amounts to 29, 31 and 33%, respectively. In general, it is close to that of the blood serum of bovine fetuses - 30, 35 and 36%. The power of the influence of the liver and kidney extracts of the bovine fetuses is significantly lower and comparable to that of the blood serum of the cows themselves: 25, 23 and 20%, although it is reliable.

Detecting metabolic differences in fetal and adult sheep adipose and skeletal muscle tissues.

The primary metabolic pathway required to produce ATP differs as a result of tissue type, developmental stage and substrate availability. We utilized molecular and histological techniques to define the metabolic status in foetal and adult, adipose and skeletal muscle tissues. Redox ratios of these tissues were also determined optically by two-photon microscopy. Adult perirenal adipose tissue had a higher optical redox ratio than fetal perirenal adipose tissue, which aligned with glycolysis being used for ATP production; whereas adult skeletal muscle had a lower optical redox ratio than fetal skeletal muscle, which aligned with oxygen demanding oxidative phosphorylation activity being utilized for ATP production. We have compared traditional molecular and microscopy techniques of metabolic tissue characterization with optical redox ratios to provide a more comprehensive report on the dynamics of tissue metabolism.