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Introduction : À ce jour, la césarienne demeure une chirurgie majeure afin de réduire les risques de mortalité fœtale et maternelle. D’ailleurs, entre 11 et 15 % des nouvelles mères développeront des douleurs et des complications au site de leur cicatrice. Quelques solutions thérapeutiques existent pour le traitement des cicatrices problématiques douloureuses. Cependant, ces solutions sont souvent modestement soutenues par la littérature. L’objectif primaire de cette étude était de décrire et d’explorer les effets de l’une de ces solutions soit la mobilisation des tissus cicatriciels de la cicatrice de césarienne. Méthode : Une étude de fiabilité et une étude descriptive exploratoire de type « preuve de concept » ont été réalisées. Des femmes âgées de 18 à 40 ans ayant subi au moins une césarienne ont été recrutées. Une ostéopathe expérimentée a effectué une mobilisation standardisée des tissus cicatriciels 1x/semaine pendant deux semaines. La qualité cicatricielle et ses caractéristiques douloureuses, les propriétés viscoélastiques, les seuils de douleur à la pression et de sensibilité au toucher léger ont été mesurés avant et après chaque séance. Le W de Kendall et le d de Cohen ont été générés pour déterminer la taille des effets pour chacune des mesures. Des tests de corrélation et de comparaison paramétriques ou non-paramétriques (en fonction de la distribution des variables) ont également été utilisés. Résultats : Cinquante et une participantes ont terminé l’une ou l’autre des études. La fiabilité intra et inter juges du MyotonPRO s’est révélée bonne à excellente (ICC 0,99-1,00 et 0,87-0,98, respectivement). Le POSAS a montré des effets légers à modérés pour la raideur (p=0.021, d=0,43), le relief (p<0,001, d=0,28), la surface (p=0,040, d=0,36), la souplesse (p=0,007, d=0,52) et l’opinion des participantes (p=0,001, d=0,62). Les mobilisations augmenteraient l’élasticité (p<0,001, W=0,11), diminueraient la raideur (p<0,001, W=0,30) et amélioreraient le seuil de, Introduction: To this day, Caesarean section (C-section) remains a major surgery to reduce the risk of fetal and maternal mortality. Moreover, between 11 and 15% of new mothers will develop pain and complications at the site of their scar. Some therapeutic solutions exist for the treatment of painful problematic scars; however, these are often modestly supported by the literature. The primary objective of this study was to describe and explore the effects of one solution, i.e., mobilization of tissue in the C-section scar. Method: A reliability study and a descriptive exploratory "proof of concept" study were performed. Women aged 18 to 40 years who had undergone at least one C-section were recruited. An experienced osteopath performed standardized scar tissue mobilization once per week for 2 weeks. Scar characteristics, including viscoelastic properties, pressure pain thresholds and light touch sensitivity thresholds were measured before and after each session. Intraclass correlation coefficients, Kendall's W and Cohen's d for overall effect sizes, Wilcoxon signed rank test, paired Student's t test, and Friedman tests with Dunn-Bonferroni adjustment, were performed. Results: Fifty-one participants completed one of the studies. Intra- and inter evaluator reliability of the MyotonPRO was good to excellent (ICC 0.99-1.00 and 0.87-0.98, respectively). The POSAS showed small to moderate effects for stiffness (p=0.021, d=0.43), relief (p<0.001, d=0.28), area (p=0.040, d=0.36), flexibility (p=0.007, d=0.52), and participant opinion (p=0.001, d=0.62). Mobilizations increased elasticity (p<0.001, W=0.11), decreased stiffness (p<0.001, W=0.30), and improved pressure pain threshold (p<0.001, W=0.10). Friedman tests showed decreased tone and mechanical stress relaxation time, and increased threshold to light touch (all p<0.05, W<0.10). There was no significant difference in creep before versus following treatment (p=0.09). Conclusion: Our results show that two sessi

Even after several decades of quiescent storage in the ovary, the female germ cell is capable of reinitiating transcription to build the reserves that are essential to support early embryonic development. In the current model of mammalian oogenesis, there exists bilateral communication between the gamete and the surrounding cells that is limited to paracrine signaling and direct transfer of small molecules via gap junctions existing at the end of the somatic cells' projections that are in contact with the oolemma. The purpose of this work was to explore the role of cumulus cell projections as a means of conductance of large molecules, including RNA, to the mammalian oocyte. By studying nascent RNA with confocal and transmission electron microscopy in combination with transcript detection, we show that the somatic cells surrounding the fully grown bovine oocyte contribute to the maternal reserves by actively transferring large cargo, including mRNA and long noncoding RNA. This occurrence was further demonstrated by the reconstruction of cumulus-oocyte complexes with transfected cumulus cells transferring a synthetic transcript. We propose selective transfer of transcripts occurs, the delivery of which is supported by a remarkable synapselike vesicular trafficking connection between the cumulus cells and the gamete. This unexpected exogenous contribution to the maternal stores offers a new perspective on the determinants of female fertility.

Alternative splicing as a mean to control gene expression and diversify function is suspected to considerably influence drug response and clearance. We report the quantitative expression profiles of the human UGT genes including alternatively spliced variants not previously annotated established by deep RNA-sequencing in tissues of pharmacological importance. We reveal a comprehensive quantification of the alternative UGT transcriptome that differ across tissues and among individuals. Alternative transcripts that comprise novel in-frame sequences associated or not with truncations of the 5’ and/or 3’ termini, significantly contribute to the total expression levels of each UGT1 and UGT2 gene averaging 21% in normal tissues, with expression of UGT2 variants surpassing those of UGT1. Quantitative data expose preferential tissue expression patterns and remodelling in favour of alternative variants upon tumorigenesis. These complex alternative splicing programs have the strong potential to contribute to interindividual variability in drug metabolism in addition to diversify the UGT proteome.

Alternative splicing as a mean to control gene expression and diversify function is suspected to considerably influence drug response and clearance. We report the quantitative expression profiles of the human UGT genes including alternatively spliced variants not previously annotated established by deep RNA-sequencing in tissues of pharmacological importance. We reveal a comprehensive quantification of the alternative UGT transcriptome that differ across tissues and among individuals. Alternative transcripts that comprise novel in-frame sequences associated or not with truncations of the 5′- and/or 3′- termini, significantly contribute to the total expression levels of each UGT1 and UGT2 gene averaging 21% in normal tissues, with expression of UGT2 variants surpassing those of UGT1. Quantitative data expose preferential tissue expression patterns and remodeling in favor of alternative variants upon tumorigenesis. These complex alternative splicing programs have the strong potential to contribute to interindividual variability in drug metabolism in addition to diversify the UGT proteome.

So far, the characteristics of a good quality egg have been elusive, similar to the nature of the physiological, cellular, and molecular cues leading to its production both in vivo and in vitro. Current understanding highlights a strong and complex interdependence between the follicular cells and the gamete. Secreted factors induce cellular responses in the follicular cells, and direct exchange of small molecules from the cumulus cells to the oocyte through gap junctions controls meiotic arrest. Studying the interconnection between the cumulus cells and the oocyte, we previously demonstrated that the somatic cells also contribute transcripts to the gamete. Here, we show that these transcripts can be visualized moving down the transzonal projections (TZPs) to the oocyte, and that a time course analysis revealed progressive RNA accumulation in the TZPs, indicating that RNA transfer occurs before the initiation of meiosis resumption under a timetable fitting with the acquisition of developmental competence. A comparison of the identity of the nascent transcripts trafficking in the TZPs, with those in the oocyte increasing in abundance during maturation, and that are present on the oocyte's polyribosomes, revealed transcripts common to all three fractions, suggesting the use of transferred transcripts for translation. Furthermore, the removal of potential RNA trafficking by stripping the cumulus cells caused a significant reduction in maturation rates, indicating the need for the cumulus cell RNA transfer to the oocyte. These results offer a new perspective to the determinants of oocyte quality and female fertility, as well as provide insight that may eventually be used to improve in vitro maturation conditions.

Some embryos exhibit better survival potential to cryopreservation than others. The cause of such a phenotype is still unclear and may be due to cell damage during cryopreservation, resulting from overaccumulation and composition of lipids. In cattle embryos, in vitro culture conditions have been shown to impact the number of lipid droplets within blastomeres. Thus far, the impact of breed on embryonic lipid content has not been studied. In the present study were compared the colour, lipid droplet abundance, lipid composition, mitochondrial activity and gene expression of in vivo-collected Jersey breed embryos, which are known to display poor performance post-freezing, with those of in vivo Holstein embryos, which have good cryotolerance. Even when housed and fed under the same conditions, Jersey embryos were found to be darker and contain more lipid droplets than Holstein embryos, and this was correlated with lower mitochondrial activity. Differential expression of genes associated with lipid metabolism and differences in lipid composition were found. These results show genetic background can impact embryonic lipid metabolism and storage.

A comprehensive view of the human UDP-glucuronosyltransferase (UGT) transcriptome is a prerequisite to the establishment of an individual's UGT metabolic glucuronidation signature. Here, we uncover the transcriptome landscape of the 10 human UGT gene loci in normal and tumoral metabolic tissues by targeted RNA next-generation sequencing. Alignment on the human hg19 reference genome identifies 234 novel exon-exon junctions. We recover all previously known UGT1 and UGT2 enzyme-coding transcripts and identify over 130 structurally and functionally diverse novel UGT variants. We further expose a revised genomic structure of UGT loci and provide a comprehensive repertoire of transcripts for each UGT gene. Data also uncover a remodelling of the UGT transcriptome occurring in a tissue- and tumor-specific manner. The complex alternative splicing program regulating UGT expression and protein functions is likely critical in determining detoxification capacity of an organ and stress-related responses, with significant impact on drug responses and diseases.

Now recognised as part of the cellular transcriptome, the function of long non-coding (lnc) RNA remains unclear. Previously, we found that some lncRNA molecules in bovine embryos are highly responsive to culture conditions. In view of a recent demonstration that lncRNA may play a role in regulating important functions, such as maintenance of pluripotency, modification of epigenetic marks and activation of transcription, we sought evidence of its involvement in embryogenesis. Among the numerous catalogued lncRNA molecules found in oocytes and early embryos of cattle, three candidates chosen for further characterisation were found unexpectedly in the cytoplasmic compartment rather than in the nucleus. Transcriptomic survey of subcellular fractions found these candidates also associated with polyribosomes and one of them spanning transzonal projections between cumulus cells and the oocyte. Knocking down this transcript in matured oocytes increased developmental rates, leading to larger blastocysts. Transcriptome and methylome analyses of these blastocysts showed concordant data for a subset of four genes, including at least one known to be important for blastocyst survival. Functional characterisation of the roles played by lncRNA in supporting early development remains elusive. Our results suggest that some lncRNAs play a role in translation control of target mRNA. This would be important for managing the maternal reserves within which is embedded the embryonic program, especially before embryonic genome activation.

So far, the characteristics of a good quality egg have been elusive, similar to the nature of the physiological, cellular, and molecular cues leading to its production both in vivo and in vitro. Current understanding highlights a strong and complex interdependence between the follicular cells and the gamete. Secreted factors induce cellular responses in the follicular cells, and direct exchange of small molecules from the cumulus cells to the oocyte through gap junctions controls meiotic arrest. Studying the interconnection between the cumulus cells and the oocyte, we previously demonstrated that the somatic cells also contribute transcripts to the gamete. Here, we show that these transcripts can be visualized moving down the transzonal projections (TZPs) to the oocyte, and that a time course analysis revealed progressive RNA accumulation in the TZPs, indicating that RNA transfer occurs before the initiation of meiosis resumption under a timetable fitting with the acquisition of developmental competence. A comparison of the identity of the nascent transcripts trafficking in the TZPs, with those in the oocyte increasing in abundance during maturation, and that are present on the oocyte's polyribosomes, revealed transcripts common to all three fractions, suggesting the use of transferred transcripts for translation. Furthermore, the removal of potential RNA trafficking by stripping the cumulus cells caused a significant reduction in maturation rates, indicating the need for the cumulus cell RNA transfer to the oocyte. These results offer a new perspective to the determinants of oocyte quality and female fertility, as well as provide insight that may eventually be used to improve in vitro maturation conditions.