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Human Reproduction Update Aug 2022The many manipulations and processes used in ART coincide with the timing of epigenetic reprogramming and imprinting during female gametogenesis and pre-implantation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The many manipulations and processes used in ART coincide with the timing of epigenetic reprogramming and imprinting during female gametogenesis and pre-implantation embryo development, leading to concerns that the actual ART could negatively affect epigenetic reprogramming and imprinting in gametes and early embryos. A growing body of literature suggests that ART may affect epigenetic marks, such as DNA methylation, in the fetus and placenta. Potentially, this may be responsible later in life for the increased risk of adverse outcomes associated with ART. Unfortunately, the conclusions are inconsistent and, despite the increasing usage of ART, its safety at the epigenetic level is still not established.
OBJECTIVE AND RATIONALE
To examine whether ART is associated with DNA methylation modifications and if these modifications persist throughout life, we provide an update on the current understanding of epigenetic reprogramming in human gametes and embryos, and then focus on the assessment of fetal and postnatal DNA methylation modifications that may remain until adulthood following the use of ART in humans.
SEARCH METHODS
We reviewed studies using targeted or epigenome-wide techniques to assess the DNA methylation patterns of the conceptus after ART compared with natural conceptions. A search for relevant studies was performed in the PubMed and EMBASE databases on 15 July 2021 with an extensive search equation. Studies on animals, gametes and embryos were subsequently excluded. After an in-depth review of full-text articles, studies on specific populations with imprinting disorders were removed and not further discussed. Before comprehensive analysis, the risk of bias of each included study was assessed with the Newcastle-Ottawa scale and quality of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations criteria.
OUTCOMES
In total, 928 records were initially identified, and 51 were finally included in the systematic review. Given the variability in the genomic scale at which DNA methylation was measured in the different studies, they were separated into two categories: targeted DNA methylation or genome-wide DNA methylation study. The present systematic review has made it possible to assess a substantial number of children since more than 4000 DNA methylation profiles of ART concepti were compared to more than 7000 controls. There is evidence that ART conception is associated with aberrant DNA methylation in imprinted loci and other genes in various tissues. One isolated modification notably occur in the paternally expressed gene 1/mesoderm-specific transcript homologue (PEG1/MEST) region, and we cannot rule out other studied sequences owing to the heterogeneity of the evidence base.
WIDER IMPLICATIONS
Differences in DNA methylation after ART conceptions are modest, and the functional relevance in adult tissues is unknown. Functional effects in terms of gene expression as well as the roles of other epigenetic marks need to be further explored. Moreover, there is little overlap of findings obtained in targeted and genome-scale analyses owing to the lack of comparability of CpGs analyzed between both techniques. This issue also stems from small sample sizes and marked differences in methodology and cohort characteristics. Standardization of methodologies and large collaborative efforts are required to reduce the inconsistency of results and increase the robustness of findings. Finally, further studies are required to determine the contribution of parental infertility per se from the ART treatment.
Topics: Adult; Animals; Child; DNA; DNA Methylation; Female; Fertilization in Vitro; Genomic Imprinting; Humans; Infertility; Longevity; Pregnancy
PubMed: 35259267
DOI: 10.1093/humupd/dmac010 -
The World Journal of Men's Health Jul 2024The () gene is a paternally expressed imprinted gene that appears to play a role in embryo survival. The latest meta-analysis on methylation pattern in spermatozoa of...
PURPOSE
The () gene is a paternally expressed imprinted gene that appears to play a role in embryo survival. The latest meta-analysis on methylation pattern in spermatozoa of infertile patients found higher methylation in spermatozoa from infertile patients than fertile controls. To provide an updated and comprehensive systematic review and meta-analysis on the gene methylation pattern in patients with abnormal sperm parameters compared to men with normal parameters.
MATERIALS AND METHODS
This meta-analysis was registered in PROSPERO (CRD42023397056) and performed following the MOOSE guidelines for Meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Only original articles evaluating gene methylation in spermatozoa from patients with infertility or abnormalities in one or more sperm parameters compared to fertile or normozoospermic men were included.
RESULTS
Of 354 abstracts evaluated for eligibility, only 6 studies were included in the quantitative synthesis, involving a total of 301 patients and 163 controls. Our analysis showed significantly higher levels of gene methylation in patients compared with controls (standard mean difference [SMD] 2.150, 95% confidence interval [CI] 0.377, 3.922; p=0.017), although there was significant heterogeneity between studies (Q-value=239.90, p<0.001; I²=97.91%). No significant evidence of publication bias was found, although one study was sensitive enough to skew the results, leading to a loss of significance (SMD 1.543, 95% CI -0.300, 3.387; p=0.101). In meta-regression analysis, we found that the results were independent of both ages (p=0.6519) and sperm concentration (p=0.2360).
CONCLUSIONS
Sperm DNA methylation may be associated with epigenetic risk in assisted reproductive techniques (ART). The gene could be included in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to be analyzed in couples undergoing ART.
PubMed: 37853535
DOI: 10.5534/wjmh.230094 -
Journal of Ovarian Research Sep 2022Ovarian malignant mesoderm mixed tumor (OMMMT) is a rare clinical entity. To provide reference for the treatment and prognosis of OMMMT, we analyzed the clinical... (Review)
Review
BACKGROUND
Ovarian malignant mesoderm mixed tumor (OMMMT) is a rare clinical entity. To provide reference for the treatment and prognosis of OMMMT, we analyzed the clinical features, pathology and molecular biology characteristic of published cases.
METHODS
The English and Chinese reported cases of OMMMT were selected from PubMed, Clinical Trials.gov and CNKI database from 2000 to December 15th, 2021 following the PRISMA guidelines.
RESULTS
A total of 63 literatures including 199 OMMMT cases were included. The average age of patients at diagnosis was 56.46 years, the highest incidence age was 60-65 years, and 82% of them were menopausal women. Most patients were diagnosed in FIGO III stage (59.64%). The most common symptom of OMMMT was abdominal pain (60.5%). 61.6% of patients were accompanied by ascites, while ascites was not associated with metastatic tumor and local recurrence. The CA125 of 88.68% patients increased. The most common reported carcinomatous component and sarcomatous component were serous adenocarcinoma (44.96%) and chondrosarcoma (24.81%), respectively. Initial treatment included surgery (94.97%) and taxanes-based (55.10%) or platinum-based (85.71%) chemotherapy regimens. The median survival time of patients was 20 months. Heterologous sarcoma component did not shorten life expectancy. The optimal ovarian tumor cell debulking surgery (OOTCDS), radiotherapy and chemotherapy could significantly prolong the median survival time of patients. Furthermore, platinum drugs could significantly prolong the survival time after comparing various chemotherapy schemes. Besides, the combination of platinum and taxanes was therapeutically superior to the combination of platinum and biological alkylating agents.
CONCLUSION
The OOTCDS and platinum-based chemotherapy regimen can improve the prognosis of OMMMT. Targeted therapy might become a new research direction in the future. Since the elderly patients are the majority, the toxicity of new drugs on the elderly patients is more noteworthy.
Topics: Aged; Alkylating Agents; Carcinoma; Female; Humans; Mesoderm; Middle Aged; Ovarian Neoplasms; Taxoids
PubMed: 36114551
DOI: 10.1186/s13048-022-01037-6 -
Human Reproduction Update 2014Increasing numbers of children are being conceived by assisted reproductive technology (ART). A number of studies have highlighted an altered epigenetic status in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Increasing numbers of children are being conceived by assisted reproductive technology (ART). A number of studies have highlighted an altered epigenetic status in gametes from infertile couples and the possibility of an increased risk of imprinting defects and somatic epigenetic changes in ART conceived children, but the results have been heterogeneous. We performed a systematic review of existing studies to compare the incidence of imprinting disorders and levels of DNA methylation in key imprinted genes in children conceived through in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with those in children conceived spontaneously.
METHODS
A detailed search strategy was used to conduct electronic literature searches (spanning 1978 to 2013) on Medline, EMBASE, the Cochrane Library and Web of Science. Abstracts of relevant conference papers were identified. As randomized trials are not feasible in this context, we included observational (cohort and case-control) studies comparing outcomes in children conceived through ART with those conceived spontaneously, irrespective of the language of publication. The outcome measures were DNA methylation and the incidence of imprinting disorders.
RESULTS
A total of 351 publications were identified by the initial search. Of these, 26 were excluded as duplicates and 241 were excluded after reviewing the abstracts, then of those remaining 66 were excluded after review of the full text. A total of 18 papers were included in the review. Apart from one case-control study, all were cohort studies. There was a degree of clinical heterogeneity in terms of the study population, type of infertility treatment, and samples obtained from exposed and unexposed children. DNA methylation levels were either presented as categorical data (hypo-, hyper- or normally methylated DNA) or continuous data (i.e. percentage of methylated DNA). The combined odds ratio (95% confidence intervals) of any imprinting disorder in children conceived through ART was 3.67 (1.39, 9.74) in comparison with spontaneously conceived children. Meta-analysis of data from relevant studies revealed that the weighted mean difference (95% confidence intervals) in methylation percent between IVF/ICSI versus spontaneously conceived children were as follows: H19: -0.46(-1.41, 0.49), PEG1-MEST: 0.47 (-2.07, 3.01), GRB10: -0.05 (-0.43, 0.33), IGF2: -0.15 (-1.09, 0.79), SNRPN: -0.55 (-1.55, 0.46), KvDMR/KCNQ10T1: -0.16 (-0.34, 0.02) and PEG3: -0.24 (-1.72, 1.24).
CONCLUSIONS
There was an increase in imprinting disorders in children conceived though IVF and ICSI but insufficient evidence for an association between ART and methylation in other imprinted genes. Heterogeneity in the types of fertility treatment, the imprinted regions studied, the tissues used and the methods of measurement, reduce our ability to assess the full effect of ART on DNA methylation and imprinting. More controlled studies, using standardized methodologies, in larger, better clinically defined populations are needed.
Topics: Child; Cohort Studies; DNA Methylation; Fertilization in Vitro; GRB10 Adaptor Protein; Genomic Imprinting; Humans; Infertility; Potassium Channels, Voltage-Gated; Proteins; RNA, Long Noncoding; Sperm Injections, Intracytoplasmic; snRNP Core Proteins
PubMed: 24961233
DOI: 10.1093/humupd/dmu033 -
FASEB Journal : Official Publication of... May 2017Pericytes are an integral cellular component of vascular structures. Numerous studies have investigated various stem cell types as potential sources of pericytes for... (Review)
Review
Pericytes are an integral cellular component of vascular structures. Numerous studies have investigated various stem cell types as potential sources of pericytes for application in cell-based therapy. The diverse stem cell types and variable experimental protocols of these studies make it imperative to evaluate the relevant scientific literature on the basis of a unified standard. The purpose of this systematic review is to rigorously evaluate the relevant scientific literature for conclusive evidence that stem cells can differentiate into functional pericytes. An online literature search was conducted up to July 2016. Eligible papers were evaluated on 4 pertinent criteria: ) appropriate controls, ) markers to confirm pericyte phenotype, ) techniques for assessing pericyte functionality, and ) differentiation efficiency of the protocol. Our search yielded 20 eligible studies (from 2006 to 2016), 12 of which were published in the past 5 yr. Of these 20 articles, only 1 had positive control, and 5 papers evaluated differentiation efficiency. The most commonly used pericyte markers were neuron-glial antigen 2, platelet-derived growth factor receptor-β, and α-smooth muscle actin. Three articles were associated with adipose stem cells, 4 with mesenchymal stem cells, and 7 with pluripotent stem cells, whereas the remaining 6 articles were based on other miscellaneous stem cell types. Stem cells can serve as a potential source of pericytes, but there should be standardized guidelines in future studies for assessing pericyte differentiation.-Xu, J., Gong, T., Heng, B. C., Zhang, C. F. A systematic review: differentiation of stem cells into functional pericytes.
Topics: Adipocytes; Animals; Cell Differentiation; Coculture Techniques; Endothelial Cells; Humans; Pericytes; Stem Cells
PubMed: 28119398
DOI: 10.1096/fj.201600951RRR -
Current Stem Cell Research & Therapy 2017Adult mesenchymal stem cells (MSCs) were first isolated from bone marrow by Friedenstein in 1976. These cells were clonogenic, non-haematopoietic, and able to replicate... (Review)
Review
BACKGROUND
Adult mesenchymal stem cells (MSCs) were first isolated from bone marrow by Friedenstein in 1976. These cells were clonogenic, non-haematopoietic, and able to replicate extensively in vitro. The fields of regenerative medicine and tissue engineering have grown dramatically since their inception. In the decades since, MSCs have been identified from mesoderm-, endoderm- and ectoderm-derived tissues. In light of our ageing population, the need for effective cell-based therapies for tissue repair and regeneration is ever-expanding.
OBJECTIVES
The purpose of this systematic review was to summarise evidence from the most recent studies outlining different sources of adult MSCs and their suitability in musculoskeletal applications.
METHODS
Online published articles were searched for using the PubMed/MEDLINE and Ovid databases, and relevant articles fulfilling the pre-defined eligibility criteria were analysed.
RESULTS
To date, MSCs have been isolated from a number of adult tissues, including trabecular bone, adipose tissue, bone marrow, synovium, dermis, periodontal ligament, dental pulp, bursa and the umbilical cord. Bone marrow MSCs are currently considered the gold standard, with which newly discovered sources are compared on the basis of their renewal capabilities and multipotency. Furthermore, MSCs have been successful in the regeneration of osteonecrosis, osteoarthritis, bony defects, fracture remodeling and so on.
CONCLUSION
Unfortunately, significant hurdles remain and will need to be overcome before tissue engineering using MSCs becomes routine in clinical practice. Thus, further research and understanding are required into the safe and effective sourcing and application of mesenchymal stem cells in musculoskeletal applications.
Topics: Adult Stem Cells; Cell Differentiation; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Musculoskeletal System; Regenerative Medicine; Tissue Engineering
PubMed: 28595566
DOI: 10.2174/1574888X12666170608124303 -
International Journal of Environmental... Dec 2019Physical, chemical, and social environments adversely affect the molecular process and results in cell signal transduction and the subsequent transcription factor...
DNA Methylation of Candidate Genes (ACE II, IFN-γ, AGTR 1, CKG, ADD1, SCNN1B and TLR2) in Essential Hypertension: A Systematic Review and Quantitative Evidence Synthesis.
Physical, chemical, and social environments adversely affect the molecular process and results in cell signal transduction and the subsequent transcription factor dysregulation, leading to impaired gene expression and abnormal protein synthesis. Stressful environments such as social adversity, isolation, sustained social threats, physical inactivity, and highly methylated diets predispose individuals to molecular level alterations such as aberrant epigenomic modulations that affect homeostasis and hemodynamics. With cardiovascular disease as the leading cause of mortality in the US and blacks/African Americans being disproportionately affected by hypertension (HTN) which contributes substantially to these deaths, reflecting the excess mortality and survival disadvantage of this sub-population relative to whites, understanding the molecular events, including epigenomic and socio-epigenomic modulations, is relevant to narrowing the black-white mortality risk differences. We aimed to synthesize epigenomic findings in HTN namely (a) angiotensin-converting enzyme 2 (ACE II) gene, (b) Toll-like receptor 2 (TLR2) gene, (c) interferon γ (IFN-γ) gene, and (d) Capping Actin Protein, Gelosin-Like () , adducin 1(ADD1) gene, (e) Tissue inhibitor of metalloproteinase 3 (), (f) mesoderm specific transcript (MEST) loci, (g) sodium channel epithelial 1 alpha subunit 2 (SCNN1B), (h) glucokinase (CKG) gene (i) angiotensin II receptor, type1 (AGTR1), and DNA methylation (mDNA). A systematic review and quantitative evidence synthesis (QES) was conducted using Google Scholar and PubMed with relevant search terms. Data were extracted from studies on: (a) Epigenomic modulations in HTN based on ACE II (b) TLR2, (c) IFN-γ gene, (d) , ADD1, , MEST loci, and mDNA. The random-effect meta-analysis method was used for a pooled estimate of the common effect size, while z statistic and I^2 were used for the homogeneity of the common effect size and between studies on heterogeneity respectively. Of the 642 studies identified, five examined hypermethylation while seven studies assessed hypomethylation in association with HTN. The hypermethylation of ACE II, SCNN1B, CKG, IFN-γ gene, and miR-510 promoter were associated with hypertension, the common effect size (CES) = 6.0%, 95% CI, -0.002-11.26. In addition, the hypomethylation of TLR2, IFN-γ gene, ADD1, AGTR1, and GCK correlated with hypertension, the CES = 2.3%, 95% CI, -2.51-7.07. The aberrant epigenomic modulation of ACE II, TLR2, IFN-γ, AGTR1, and GCK correlated with essential HTN. Transforming the environments resulting from these epigenomic lesions will facilitate early intervention mapping in reducing HTN in the US population, especially among socially disadvantaged individuals, particularly racial/ethnic minorities.
Topics: DNA Methylation; Essential Hypertension; Female; Genotype; Humans
PubMed: 31805646
DOI: 10.3390/ijerph16234829 -
Head and Neck Pathology Dec 2020The microenvironment of oral cancer is highly dynamic and has been proved to affect tumor progression. Pericytes are blood vessels surrounding cells that have recently...
The microenvironment of oral cancer is highly dynamic and has been proved to affect tumor progression. Pericytes are blood vessels surrounding cells that have recently gained attention for their roles in vascular and cancer biology. The objective of the present study was to survey the scientific literature for conclusive evidence about whether pericytes are part of blood vessels in oral squamous cell carcinoma (OSCC) and their roles in the tumor microenvironment and clinical outcomes. A systematic electronic search was undertaken in Medline Ovid, PubMed, Web of Science, and Scopus. Eligibility criteria were: publications adopting in vivo models of OSCC that included pericyte detection and assessment by pericyte markers (e.g., α-smooth muscle actin, neuron-glial antigen 2 and platelet-derived growth factor receptor-β). The search yielded seven eligible studies (from 2008 to 2018). The markers most commonly used for pericyte detection were α-smooth muscle actin and neuron-glial antigen 2. The studies reviewed showed the presence of immature vessels exhibiting a reduction of pericyte coverage in OSCC and indicated that anti-cancer therapies could contribute to vessel normalization and pericyte regain. The pericyte population is significantly affected during OSCC development and cancer therapy. While these findings might suggest a role for pericytes in OSCC progression, the limited data available do not allow us to conclude whether they modify the tumor microenvironment and clinical outcome.
Topics: Animals; Humans; Mouth Neoplasms; Pericytes; Squamous Cell Carcinoma of Head and Neck; Tumor Microenvironment
PubMed: 32506378
DOI: 10.1007/s12105-020-01188-2 -
World Journal of Stem Cells Nov 2019Mesenchymal stem cells are pluripotent cells that have the ability to generate cells from a cell line or in other cell types from different tissues but from the same...
BACKGROUND
Mesenchymal stem cells are pluripotent cells that have the ability to generate cells from a cell line or in other cell types from different tissues but from the same origin. Although those cells have more limited differentiation capacity than embryonic stem cells, they are easily obtained from somatic tissue and can be grown in large quantities. This characteristic of undifferentiated stem cells differentiating into different cell lines arouses strategies in regenerative medicine for the treatment of different diseases such as neurodegenerative diseases.
AIM
To evaluate the cell differentiation capacity of human breastmilk stem cells for the three germ layers by a systematic review.
METHODS
The searched databases were PubMed, EMBASE, OVID, and COCHRANE LIBRARY, published between 2007 and 2018 in the English language. All were studies for analysis of the "cell differentiation potential" in the literature using the keywords "human breastmilk," "stem cells," and keywords combined with the Boolean operator "NOT" were used to exclude those articles that had the word "CANCER" and their respective synonyms, which were previously consulted according to medical subject heading terms. PRISMA 2009 guidelines were followed in this study.
RESULTS
A total of 315 titles and abstracts of articles were examined. From these, 21 were in common with more than one database, leaving 294 articles for analysis. Of that total, five publications met the inclusion criteria. When analyzing the publications, it was demonstrated that human breastmilk stem cells have a high cellular plasticity, exhibiting the ability to generate cells of all three germ layers, endoderm, mesoderm, and ectoderm, demonstrating their stemness. Those cells expressed the genes, TRA-1-60/81, octamer-binding transcription factor 4, and NANOG, of which NANOG, a critical regulator for self-renewal and maintenance, was the most highly expressed. Those cells have the ability to differentiate into adipocytes, chondrocytes, osteocytes, oligodendrocytes, astrocytes, and neurons as well hepatocytes, β-pancreatic cells, and cardiomyocytes.
CONCLUSION
Although the literature has been scarce, the pluripotentiality of these cells represents great potential for tissue engineering and cellular therapy. Further studies for safe clinical translation are needed.
PubMed: 31768226
DOI: 10.4252/wjsc.v11.i11.1005 -
Neuro-degenerative Diseases 2022Several studies indicate the role of mesenchymal stem cells (MSCs) as an important tool in regenerative medicine associated with injuries that affect the central nervous...
INTRODUCTION
Several studies indicate the role of mesenchymal stem cells (MSCs) as an important tool in regenerative medicine associated with injuries that affect the central nervous system (CNS). The MSCs have the capacity to differentiate into cells of the embryonic tissue, such as the mesoderm. So, these cells can be found in a variety of tissues. Also, the MSCs can release immunomodulatory and neurotrophic factors performance as inflammation mediators operating in injured tissue regeneration. Furthermore, they can differentiate into neural-like cells in vitro. Thereby, because of the high immunomodulatory role of MSCs, this review sought to describe the main immunomodulatory mechanisms performed by MSCs in CNS recovery after tissue injury or neurodegenerative diseases.
METHODS
PubMed and ScienceDirect were searched between January 2011 to March 2021, and 43 articles met the criteria of the review.
RESULTS
This systematic review indicates that MSCs were used in vivo experimental multiple sclerosis, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, ischemic stroke, and traumatic brain injury. The treatment MSCs were usually from human origin, derived from bone marrow, and administered intravenously.
CONCLUSION
It was shown that MSCs, independent from origin or administration pathway, can reduce inflammation and help in the recovery and preservation of injured neural tissue. Thus, the use of MSCs represents a potential therapeutic option in the treatment of neurological disorders mediated by inflammatory processes.
Topics: Humans; Mesenchymal Stem Cells; Neurodegenerative Diseases; Central Nervous System; Multiple Sclerosis; Parkinson Disease
PubMed: 36398461
DOI: 10.1159/000528036