Is the phosphoinositol 1,3-kinase/protein kinase B (PI3K/AKT) pathway expression profile in cumulus cells (CCs) a potential marker of oocyte competence and predictive of pregnancy outcome?
Eleven ...genes (AKT1, ARHGEF7, BCL2L1, CCND1, E2F1, HRAS, KCNH2, PIK3C2A, SHC1, SOS1 and SPP1) in the PI3K/AKT pathway were significantly down-regulated in CCs from oocytes that went on to produce a pregnancy compared to CCs associated with a negative outcome.
The PI3K/AKT pathway plays a pivotal role in the interdependence and continuous feedback between the oocyte and CCs.
The expression analysis of 92 transcripts in the PI3K/AKT pathway in CCs from patients with negative or positive pregnancy outcome, after single embryo transfer, was performed. Mouse CCs target gene expression was conducted to associate the expression profile of PI3K/AKT pathway to oocyte developmental profile.
Fifty-five good prognosis IVF patients who had been referred to IVF or intracytoplasmic sperm injection treatment for male-factor infertility or tubal disease were enroled. CCs from single cumulus-oocyte complexes (COCs) from 16 patients who underwent a single embryo transfer were analyzed. Twenty-five CD-1 mice were used to assess gene expression in CCs associated with oocytes with different competence in relation to hCG priming. A total 220 human COCs were collected. The RNA extracted from CCs of 16 selected patients was used to analyze PI3K/AKT pathway gene expression employing a 96-well custom TaqMan Array. Expression data of CCs associated to positive IVF outcome were compared to data from negative outcome samples. Mice were sacrificed after 9, 12, 15, 21 and 24 h post-hCG administration to obtain CCs from MII oocytes with different developmental competence. Akt1, Bcl2l2 and Shc1 expression were tested in the collected mouse CCs. In addition, the expression of upstream regulator ESR1, the gene encoding for the oestrogen receptor ERβ, and the downstream effectors of the pathway FOXO1, FOXO3 and FOXO4 was evaluated in human and mouse samples.
Transcripts involved in the PI3K Signaling Pathway were selectively modulated according to the IVF/ICSI outcome of the oocyte. Eleven transcripts in this pathway were significantly down-regulated in all samples of CCs from oocytes with positive when compared those with a negative outcome. These outcomes were confirmed in mouse CCs associated with oocytes at different maturation stages. Expression data revealed that the down-regulation of ESR1 could be related to oocyte competence and is likely to be the driver of expression changes highlighted in the PI3K/AKT pathway.
Small sample size and retrospective design.
The CCs expression profile of PI3K/AKT signaling genes, disclosed a specific CCs gene signature related to oocyte competence. It could be speculated that CCs associated with competent oocytes have completed their role in sustaining oocyte development and are influencing their fate in response to metabolic and hormonal changes by de-activating anti-apoptotic signals.
Supported by Merck Serono an affiliate of Merck KGaA, Darmstadt, Germany (research grant for the laboratory session; Merck KGaA reviewed the manuscript for medical accuracy only before journal submission. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors). The authors declare no conflict of interest.
To report the diagnostic accuracy of cell-free DNA (cfDNA) in maternal blood in detecting chromosomal anomalies in twin pregnancies.
Medline, Embase and Cochrane databases were searched. The ...inclusion criteria were twin pregnancies undergoing cfDNA screening for Trisomies 13, 18, 21, monosomy X0 and other sex chromosomal anomalies (SCA). The index test was represented by a positive results of cfDNA test. The reference standard was represented by the karyotype results (obtained either pre or postnatally) or, in case of negative cfDNA result, by a normal neonatal phenotype. The quality of the studies was assessed using the revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2). Summary estimates of sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-) and diagnostic odds ratio (DOR), with the corresponding 95% Confidence Intervals (95% CI), were computed using the bivariate random-effects model.
Thirty-five studies were included. cfDNA had an overall high accuracy in detecting Trisomy 21 in twin pregnancies with a sensitivity of 98.8% (95% CI 96.5-100), a specificity of 100% (95% CI 99.9-100). Sensitivity and specificity were of 94.9% (95% CI 75.6-99.1) and 100 (95% CI 99.9-100) for Trisomy 18, and 84.6% (95% C% 54.6-98.1) and 100% (95% CI 99.9-100) for Trisomy 13 . We could not compute the diagnostic accuracy of cfDNA in detecting monosomy X0 in twins, while cfDNA had a sensitivity of 100% (95% CI 71.5-100) and a specificity of 99.8% (95% CI 99.7-99.9) in detecting other SCA (11 cases). The accuracy of cfDNA in detecting Trisomy 21, 18 and 13 was similar in dichorionic and monochorionic twin pregnancies.
cfDNA has a high diagnostic accuracy in detecting Trisomy 18 and 21 in twin pregnancies, irrespective of chorionicity. Accuracy in the detection of Trisomy 13 and SCA was limited by the small number of affected cases and the difficulties in the confirmation of false negative cases in case of SCA and requires confirmation in larger studies. This article is protected by copyright. All rights reserved.
Purpose
Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy, with increasing prevalence worldwide and still unclear pathogenic mechanisms. Extracellular vesicles ...(EVs) are emerging as potential biomarkers of disease-specific pathways in metabolic disorders, but their potential role in GDM is not fully understood. Therefore, the main aim of this study was to evaluate the link between EVs and hyperglycaemia during pregnancy.
Methods
We assessed 50 GDM women and 50 controls at the third trimester of pregnancy in whom we collected demographic characteristics and clinical and anthropometric parameters. In addition, the circulating total EVs (tEVs) and their subpopulations were assessed using flow cytometry.
Results
The levels of tEVs and EVs subtypes, expressed as median and interquartile range, were not significantly different between two groups; however, adipocyte-derived EVs (aEVs) concentration, expressed as percentage, was higher in controls than in GDM women (
p
= 0.045). In addition, a significant correlation was observed between aEVs (%) and third trimester total cholesterol (
p
= 0.022) within the GDM group. Furthermore, a significant correlation between endothelial-derived EVs (eEVs) and platelet-derived EVs (pEVs) within both groups was found, as well as a significant relation between aEVs and pEVs.
Conclusions
These data, although preliminary, represent the starting point for further studies to determine the role of circulating EVs in GDM.
Placental Stem Cells from Domestic Animals Barboni, B.; Russo, V.; Berardinelli, P. ...
Cell Transplantation,
01/2018, Volume:
27, Issue:
1
Book Review, Journal Article
Peer reviewed
Open access
The field of regenerative medicine is moving toward clinical practice in veterinary science. In this context, placenta-derived stem cells isolated from domestic animals have covered a dual role, ...acting both as therapies for patients and as a valuable cell source for translational models. The biological properties of placenta-derived cells, comparable among mammals, make them attractive candidates for therapeutic approaches. In particular, stemness features, low immunogenicity, immunomodulatory activity, multilineage plasticity, and their successful capacity for long-term engraftment in different host tissues after autotransplantation, allo-transplantation, or xenotransplantation have been demonstrated. Their beneficial regenerative effects in domestic animals have been proven using preclinical studies as well as clinical trials starting to define the mechanisms involved. This is, in particular, for amniotic-derived cells that have been thoroughly studied to date. The regenerative role arises from a mutual tissue-specific cell differentiation and from the paracrine secretion of bioactive molecules that ultimately drive crucial repair processes in host tissues (e.g., anti-inflammatory, antifibrotic, angiogenic, and neurogenic factors). The knowledge acquired so far on the mechanisms of placenta-derived stem cells in animal models represent the proof of concept of their successful use in some therapeutic treatments such as for musculoskeletal disorders. In the next future, legislation in veterinary regenerative medicine will be a key element in order to certify those placenta-derived cell-based protocols that have already demonstrated their safety and efficacy using rigorous approaches and to improve the degree of standardization of cell-based treatments among veterinary clinicians.
Inositol is a carbocyclic sugar polyalcohol. By epimerization of its hydroxyl groups, nine possible stereoisomers can be generated, two of major physiological and clinical relevance: myo-inositol and ...D-chiro-inositol. Myo-inositol and D-chiro-inositol are normally stored in kidney, brain and liver and are necessary for functions, such as signal transduction, metabolic flux, insulin signaling, regulation of ion-channel permeability, stress response and embryo development. In this narrative review, we summarize the mechanisms by which myo-inositol and D-chiro-inositol can be synthesized and absorbed and their possible role in the etiopathogenesis of neural tube defects.
We performed an online search in the PubMed database using the following keywords: "inositol", "D-chiro-inositol", "myo-inositol", "neural tube defects and inositol".
Inositol requirements are partly met by dietary intake, while the rest is synthesized endogenously. Inositol deficiency may be involved in the pathogenesis of diseases, such as metabolic syndrome, spina bifida (a neural tube defect), polycystic ovary syndrome and diabetes. Supplementation of the two inositol stereoisomers, D-chiro-inositol and myo-inositol is important to prevent these conditions.
Inositol is fundamental for signal transduction in the brain, kidneys, reproductive organs and other tissues in response to neurotransmitters, hormones and growth factors. Various genes are involved in inositol metabolism and associated pathways. Altered inositol concentrations are observed in several diseases. Analysis of the genes involved in inositol metabolism may provide important information for the clinical management of these conditions.
SARS-CoV-2 is responsible for the present coronavirus pandemic and some suggestions were made about its possible artificial origin. We, therefore, compared SARS-CoV-2 with such known viruses that ...were prepared in the laboratory and other relevant natural strains to estimate their genetic relatedness.
BLAST and clustalW were used to identify and align viral sequences of SARS-CoV-2 to other animal coronaviruses (human, bat, mouse, pangolin) and related artificial constructs. Phylogenetics trees were then prepared using iTOL.
Our study supports the notion that known artificial coronaviruses, including the chimeric SL-SHC014-MA15 synthesized in 2015, differ too much from SARS-CoV-2 to hypothesize an artificial origin of the latter. On the contrary, our data support the natural origin of the COVID-19 virus, likely derived from bats, possibly transferred to pangolins, before spreading to man.
Speculations about the artificial origin of SARS-CoV-2 are most likely unfounded. On the contrary, when carefully handled, engineered organisms provide a unique opportunity to study biological systems in a controlled fashion. Biotechnology is a powerful tool to advance medical research and should not be abandoned because of irrational fears.
The UN Sustainable Development Goals (SDGs) strive to eliminate poverty, preserve the planet, and promote shared prosperity through sustainable and inclusive means by 2030. This requires the ...implementation of a diverse set of strategies to overcome challenges and foster synergies among different SDG targets, facilitating the achievement of these ambitious goals. The aim of this review is to highlight the world's progress toward SDGs with the utilization of biotechnological advancements, including targets, strategies, synergies, and challenges. We scrutinized published research articles in peer-reviewed journals, UN reports, and scientific books that were relevant to the current topic. We identified some major challenges faced by the countries, especially developing ones, in the way of sustainable progress. These include inadequate governance, fragile states, armed conflicts, rising inequality, limited economic progress, climate change, environmental degradation, and food insecurity. Biotechnological advancements contribute to sustainable resource management, environmental conservation, and ecosystem restoration. Collaboration among countries and organizations is crucial for sharing knowledge and providing technical and financial assistance to developing nations.
The prosperity of our planet relies on the cardinal concept of sustainable development. The dietary choices of humans play a pivotal role in creating a peaceful and contented world. In this context, ...the Mediterranean diet (MD) has emerged as a valuable approach to accomplishing such progress, wherein the rights of all living beings are equally honored. This review aims to analyze the significance of a plant-based diet, particularly the Mediterranean diet, in attaining sustainable development goals. A comprehensive search of the literature was conducted to gather the most reliable and published scientific evidence from books and papers. Within this research endeavor, specific Sustainable Development Goals (SDGs) are individually addressed in relation to the adoption of the Mediterranean diet as a foundational nutritional paradigm. Our research findings underscore the immense importance of the MD and advocate for its worldwide implementation to accomplish sustainable development objectives. The MD emerges as the most suitable dietary option for fostering sustainability and tranquility in our world. It is crucial to prioritize the global implementation of the MD to genuinely achieve sustainable development.
Anorexia nervosa (AN) is a severe psychiatric disorder characterized by an intense fear of gaining weight, a relentless pursuit of thinness, and a distorted body image. Recent research highlights the ...substantial contribution of genetics to AN's etiology, with genes like BDNF, SLC6A4, and DRD2 implicated. However, a comprehensive genetic test for AN diagnosis is lacking. This study aims to elucidate the biological foundations of AN, examining variants in genes associated with syndromic forms, rare variants in AN patients, and candidate genes from GWAS studies, murine models, or established molecular pathways.
The study involved 135 AN patients from Italy, diagnosed based on DSM-V criteria. A specialized Next-Generation Sequencing panel targeting 163 genes was designed. Sequencing was performed on an Illumina MiSeq System, and variants were analyzed using bioinformatics tools. Data on clinical parameters, exercise habits, and AN types were collected.
The AN cohort, predominantly female, exhibited diverse clinical characteristics. Our analysis identified gene variants associated with syndromic forms of AN, such as STRA6, NF1, MAT1A, and ABCC6. Variants were also found in known AN-related genes (CD36, DRD4, GCKR, GHRL, GRIN3B, GPR55, LEPR) and in other 16 candidate genes (A2M, AEBP1, ABHD4, ACBD7, CNTNAP, GFRAL, GRIN2D, LIPE, LMNA, NMU, PDE3B, POMC, RYR1, TNXB, TYK2, VPS13B), highlighting the complexity of AN's genetic landscape. The endocannabinoid and dopamine pathways play crucial roles. Skeletal muscle-related genes and appetite-regulating hormones also revealed potential connections. Adipogenesis-related genes suggest AN's association with subcutaneous adipose tissue deficiency.
This study provides comprehensive insights into the genetic underpinnings of AN, emphasizing the importance of multiple pathways. The identified variants contribute.
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