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1.
Int J Mol Sci ; 23(1)2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35008911

RESUMO

Changes in the female genital tract microbiome are consistently correlated to gynecological and obstetrical pathologies, and tract dysbiosis can impact reproductive outcomes during fertility treatment. Nonetheless, a consensus regarding the physiological microbiome core inside the uterine cavity has not been reached due to a myriad of study limitations, such as sample size and experimental design variations, and the influence of endometrial bacterial communities on human reproduction remains debated. Understanding the healthy endometrial microbiota and how changes in its composition affect fertility would potentially allow personalized treatment through microbiome management during assisted reproductive therapies, ultimately leading to improvement of clinical outcomes. Here, we review current knowledge regarding the uterine microbiota and how it relates to human conception.

2.
Microbiome ; 10(1): 1, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34980280

RESUMO

BACKGROUND: Previous evidence indicates associations between the female reproductive tract microbiome composition and reproductive outcome in infertile patients undergoing assisted reproduction. We aimed to determine whether the endometrial microbiota composition is associated with reproductive outcomes of live birth, biochemical pregnancy, clinical miscarriage or no pregnancy. METHODS: Here, we present a multicentre prospective observational study using 16S rRNA gene sequencing to analyse endometrial fluid and biopsy samples before embryo transfer in a cohort of 342 infertile patients asymptomatic for infection undergoing assisted reproductive treatments. RESULTS: A dysbiotic endometrial microbiota profile composed of Atopobium, Bifidobacterium, Chryseobacterium, Gardnerella, Haemophilus, Klebsiella, Neisseria, Staphylococcus and Streptococcus was associated with unsuccessful outcomes. In contrast, Lactobacillus was consistently enriched in patients with live birth outcomes. CONCLUSIONS: Our findings indicate that endometrial microbiota composition before embryo transfer is a useful biomarker to predict reproductive outcome, offering an opportunity to further improve diagnosis and treatment strategies. Video Abstract.

3.
Am J Hum Genet ; 108(12): 2238-2247, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34798051

RESUMO

Chromosome imbalance (aneuploidy) is the major cause of pregnancy loss and congenital disorders in humans. Analyses of small biopsies from human embryos suggest that aneuploidy commonly originates during early divisions, resulting in mosaicism. However, the developmental potential of mosaic embryos remains unclear. We followed the distribution of aneuploid chromosomes across 73 unselected preimplantation embryos and 365 biopsies, sampled from four multifocal trophectoderm (TE) samples and the inner cell mass (ICM). When mosaicism impacted fewer than 50% of cells in one TE biopsy (low-medium mosaicism), only 1% of aneuploidies affected other portions of the embryo. A double-blinded prospective non-selection trial (NCT03673592) showed equivalent live-birth rates and miscarriage rates across 484 euploid, 282 low-grade mosaic, and 131 medium-grade mosaic embryos. No instances of mosaicism or uniparental disomy were detected in the ensuing pregnancies or newborns, and obstetrical and neonatal outcomes were similar between the study groups. Thus, low-medium mosaicism in the trophectoderm mostly arises after TE and ICM differentiation, and such embryos have equivalent developmental potential as fully euploid ones.

4.
Elife ; 102021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34709177

RESUMO

Background: Decidualization of the uterine mucosa drives the maternal adaptation to invasion by the placenta. Appropriate depth of placental invasion is needed to support a healthy pregnancy; shallow invasion is associated with the development of severe preeclampsia (sPE). Maternal contribution to sPE through failed decidualization is an important determinant of placental phenotype. However, the molecular mechanism underlying the in vivo defect linking decidualization to sPE is unknown. Methods: Global RNA sequencing was applied to obtain the transcriptomic profile of endometrial biopsies collected from nonpregnant women who suffer sPE in a previous pregnancy and women who did not develop this condition. Samples were randomized in two cohorts, the training and the test set, to identify the fingerprinting encoding defective decidualization in sPE and its subsequent validation. Gene Ontology enrichment and an interaction network were performed to deepen in pathways impaired by genetic dysregulation in sPE. Finally, the main modulators of decidualization, estrogen receptor 1 (ESR1) and progesterone receptor B (PGR-B), were assessed at the level of gene expression and protein abundance. Results: Here, we discover the footprint encoding this decidualization defect comprising 120 genes-using global gene expression profiling in decidua from women who developed sPE in a previous pregnancy. This signature allowed us to effectively segregate samples into sPE and control groups. ESR1 and PGR were highly interconnected with the dynamic network of the defective decidualization fingerprint. ESR1 and PGR-B gene expression and protein abundance were remarkably disrupted in sPE. Conclusions: Thus, the transcriptomic signature of impaired decidualization implicates dysregulated hormonal signaling in the decidual endometria in women who developed sPE. These findings reveal a potential footprint that could be leveraged for a preconception or early prenatal screening of sPE risk, thus improving prevention and early treatments. Funding: This work has been supported by the grant PI19/01659 (MCIU/AEI/FEDER, UE) from the Spanish Carlos III Institute awarded to TGG. NCM was supported by the PhD program FDGENT/2019/008 from the Spanish Generalitat Valenciana. IMB was supported by the PhD program PRE2019-090770 and funding was provided by the grant RTI2018-094946-B-100 (MCIU/AEI/FEDER, UE) from the Spanish Ministry of Science and Innovation with CS as principal investigator. This research was funded partially by Igenomix S.L.


Assuntos
Decídua/patologia , Receptor alfa de Estrogênio/genética , Pré-Eclâmpsia/genética , Receptores de Progesterona/genética , Transdução de Sinais , Adulto , Decídua/metabolismo , Receptor alfa de Estrogênio/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Pré-Eclâmpsia/metabolismo , Gravidez , Receptores de Progesterona/metabolismo , Adulto Jovem
5.
Bioresour Technol ; 342: 125893, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34537530

RESUMO

Electroautotrophs are microorganisms that can take the electrons needed for energy generation, CO2 fixation and other metabolic reactions from a polarized electrode. They have been the focus of intense research for its application in wastewater treatment, bioelectrosynthetic processes and hydrogen generation. As a general trend, current densities produced by the electron uptake of these microorganisms are low, limiting their applicability at large scale. In this work, the electron uptake mechanisms that may operate in electroautotrophs are reviewed, aiming at finding possible causes for this low performance. Biomass yields, growth rates and electron uptake rates observed when these microorganisms use chemical electron donors are compared with those typically obtained with electrodes, to explore limitations and advantages inherent to the electroautotrophic metabolism. Also, the factors affecting biofilm development are analysed to show how interfacial interactions condition bacterial adhesion, biofilm growth and electrons uptake. Finally, possible strategies to overcome these limitations are described.

6.
Nutrients ; 13(9)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34578859

RESUMO

Osteoporosis is characterized by bone loss. The present study aims to investigate the effects of bovine colostrum (BC) on bone metabolism using ovariectomized (OVX) and orchidectomized (ORX) rat models. Twenty-seven-week-old Wistar Han rats were randomly assigned as: (1) placebo control, (2) BC supplementation dose 1 (BC1: 0.5 g/day/OVX, 1 g/day/ORX), (3) BC supplementation dose 2 (BC2: 1 g/day/OVX, 1.5 g/day/ORX) and (4) BC supplementation dose 3 (BC3: 1.5 g/day/OVX, 2 g/day/ORX). Bone microarchitecture, strength, gene expression of VEGFA, FGF2, RANKL, RANK and OPG, and bone resorption/formation markers were assessed after four months of BC supplementation. Compared to the placebo, OVX rats in the BC1 group exhibited significantly higher cortical bone mineral content and trabecular bone mineral content (p < 0.01), while OVX rats in the BC3 group showed significantly higher trabecular bone mineral content (p < 0.05). ORX rats receiving BC dose 2 demonstrated significantly higher levels of trabecular bone mineral content (p < 0.05). Serum osteocalcin in the ORX was pointedly higher in all BC supplementation groups than the placebo (BC1: p < 0.05; BC2, BC3: p < 0.001). Higher doses of BC induced significantly higher relative mRNA expression of OPG, VEGFA, FGF2 and RANKL (p < 0.05). BC supplementation improves bone metabolism of OVX and ORX rats, which might be associated with the activation of the VEGFA, FGF2 and RANKL/RANK/OPG pathways.


Assuntos
Colostro/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Animais , Densidade Óssea , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Bovinos , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Ovariectomia , Ratos , Ratos Wistar
7.
Semin Reprod Med ; 39(5-06): 227-232, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34425598

RESUMO

Unexplained infertility (UI) and recurrent implantation failure (RIF) are diagnoses based on failed pregnancy attempts within current infertility treatment models. Both diagnoses are made when fertility is unexplained based on current diagnostic methods and has no clear cause; UI is diagnosed when testing is inconclusive, and RIF is diagnosed after three failed in vitro fertilization cycles. In both cases, interventions are often introduced without an understanding of the cause of the infertility, frequently leading to frustration for patients and caregivers. Here, we review evidence to support an influence of endometrial factor in patients given these poorly defined diagnoses and possible treatments targeting the endometrium to improve outcomes in these patients.

8.
Int J Mol Sci ; 22(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34445194

RESUMO

Uterine leiomyomas represent the most common benign gynecologic tumor. These hormone-dependent smooth-muscle formations occur with an estimated prevalence of ~70% among women of reproductive age and cause symptoms including pain, abnormal uterine bleeding, infertility, and recurrent abortion. Despite the prevalence and public health impact of uterine leiomyomas, available treatments remain limited. Among the potential causes of leiomyomas, early hormonal exposure during periods of development may result in developmental reprogramming via epigenetic changes that persist in adulthood, leading to disease onset or progression. Recent developments in unbiased high-throughput sequencing technology enable powerful approaches to detect driver mutations, yielding new insights into the genomic instability of leiomyomas. Current data also suggest that each leiomyoma originates from the clonal expansion of a single transformed somatic stem cell of the myometrium. In this review, we propose an integrated cellular and molecular view of the origins of leiomyomas, as well as paradigm-shifting studies that will lead to better understanding and the future development of non-surgical treatments for these highly frequent tumors.


Assuntos
Leiomioma/patologia , Neoplasias Uterinas/patologia , Útero/patologia , Animais , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Humanos , Leiomioma/etiologia , Leiomioma/genética , Mutação , Neoplasias Uterinas/etiologia , Neoplasias Uterinas/genética , Útero/metabolismo
9.
Biomed Res Int ; 2021: 6630232, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195274

RESUMO

Background: Ischemia-reperfusion injury is one of the most critical phenomena in lung transplantation and causes primary graft failure. Its pathophysiology remains incompletely understood, although the inflammatory response and apoptosis play key roles. Lidocaine has anti-inflammatory properties. The aim of this research is to evaluate the effect of intravenous lidocaine on the inflammatory and apoptotic responses in lung ischemia-reperfusion injury. Methods: We studied the histological and immunohistochemical changes in an experimental model of lung transplantation in pigs. Twelve pigs underwent left pneumonectomy, cranial lobectomy, caudal lobe reimplantation, and 60 minutes of graft reperfusion. Six of the pigs made up the control group, while six other pigs received 1.5 mg/kg of intravenous lidocaine after induction and a 1.5 mg/kg/h intravenous lidocaine infusion during surgery. In addition, six more pigs underwent simulated surgery. Lung biopsies were collected from the left caudal lobe 60 minutes after reperfusion. We conducted a double study on these biopsies and assessed the degree of inflammation, predominant cell type (monocyte-macrophage, lymphocytes, or polymorphous), the degree of congestion, and tissue edema by hematoxylin and eosin stain. We also conducted an immunohistochemical analysis with antibodies against CD68 antigens, monocyte chemoattractant protein-1 (MCP-1), Bcl-2, and caspase-9. Results: The lungs subjected to ischemia-reperfusion injury exhibited a higher degree of inflammatory infiltration. The predominant cell type was monocyte-macrophage cells. Both findings were mitigated by intravenous lidocaine administration. Immunohistochemical detection of anti-CD68 and anti-MCP-1 showed higher infiltration in the lungs subjected to ischemia-reperfusion injury, while intravenous lidocaine decreased the expression. Ischemia-reperfusion induced apoptotic changes and decreased Bcl-2 expression. The group treated with lidocaine showed an increased number of Bcl-2-positive cells. No differences were observed in caspase-9 expression. Conclusions: In our animal model, intravenous lidocaine was associated with an attenuation of the histological markers of lung damage in the early stages of reperfusion.


Assuntos
Apoptose/efeitos dos fármacos , Inflamação/tratamento farmacológico , Injeções Intravenosas , Lidocaína/administração & dosagem , Pulmão/cirurgia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Anti-Inflamatórios/administração & dosagem , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biópsia , Caspase 9/metabolismo , Quimiocina CCL2/metabolismo , Hemodinâmica , Pulmão/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Suínos
10.
Fertil Steril ; 116(1): 13-14, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34148581

RESUMO

The goal of this Views and Interviews series was to bring together the thought leaders in the field and envision what the laboratory will look like in the future. This consensus piece strives to take the thoughts of those leaders and develop themes and concepts that will be significant in the laboratory in the coming years.


Assuntos
Andrologia/tendências , Inteligência Artificial/tendências , Serviços de Laboratório Clínico/tendências , Fertilização In Vitro/tendências , Infertilidade/terapia , Medicina Reprodutiva/tendências , Automação Laboratorial , Consenso , Difusão de Inovações , Feminino , Previsões , História do Século XXI , Humanos , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Masculino , Gravidez
11.
Fertil Steril ; 116(1): 2-3, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34148585

RESUMO

The in vitro fertilization and andrology laboratories are at the center of assisted reproductive technologies and the place where technicians and embryologists manipulate gametes and preimplantation-stage embryos with the goal of achieving the best embryo for transfer. Through the years, these laboratories have seen developments in technique, technology, and testing. The goal of this Views and Interviews series is to bring together the thought leaders in the field and envision what the laboratories will look like in the next 10 years.


Assuntos
Andrologia/tendências , Serviços de Laboratório Clínico/tendências , Fertilização In Vitro/tendências , Infertilidade/terapia , Medicina Reprodutiva/tendências , Difusão de Inovações , Feminino , Previsões , História do Século XXI , Humanos , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Masculino , Gravidez
12.
Fertil Steril ; 116(1): 4-12, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34148588

RESUMO

The aim of this article is to gather 9 thought leaders and their team members to present their ideas about the future of in vitro fertilization and the andrology laboratory. Although we have seen much progress and innovation in the laboratory over the years, there is still much to come, and this article looks at what these leaders think will be important in the future development of technology and processes in the laboratory.


Assuntos
Andrologia/tendências , Serviços de Laboratório Clínico/tendências , Fertilização In Vitro/tendências , Infertilidade/terapia , Medicina Reprodutiva/tendências , Andrologia/legislação & jurisprudência , Automação Laboratorial , Serviços de Laboratório Clínico/legislação & jurisprudência , Difusão de Inovações , Feminino , Fertilização In Vitro/legislação & jurisprudência , Previsões , História do Século XXI , Humanos , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Masculino , Formulação de Políticas , Gravidez , Medicina Reprodutiva/legislação & jurisprudência
13.
F S Sci ; 2(1): 88-100, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34124698

RESUMO

Scientists from multiple basic disciplines and an international group of physician-scientists from the field of obstetrics and gynecology presented recent studies and discussed new and evolving theories of uterine fibroid etiology, growth and development at The Basic Science of the Uterine Fibroids meeting, sponsored by the Campion Fund and the National Institute of Environmental Health Sciences. The purpose was to share up-to date knowledge and to stimulate new concepts regarding the basic molecular biology and pathophysiology of uterine fibroids, and to promote future collaborations. The meeting was held at the National Institutes of Environmental Health Sciences in North Carolina on February 28, 2020. Speakers reviewed recent advances in cellular and molecular processes that contribute to fibroid growth and new opportunities for treatment. At the conclusion of the conference, attendees identified important new directions for future research.

14.
Reprod Sci ; 28(11): 3171-3180, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34033112

RESUMO

Our aim was to determine prospectively whether increased body mass index (BMI) affects endometrial receptivity through displacement of the window of implantation (dWOI) using the endometrial receptivity analysis (ERA), and whether this effect is BMI-dependent. We recruited a population of 170 infertile women with a normal uterus and no clinical history of recurrent miscarriage or implantation failure. These women were divided into four groups according to BMI: normal weight (18.5-24.9 kg/m2; n = 44), overweight (25-29.9 kg/m2; n = 29), class I obese (30.0-34.9 kg/m2; n = 54), and class II and III obese (> 35 kg/m2; n = 43). We also assigned the patients to one of two larger BMI cohorts: non-obese (normal weight and overweight; n = 73) and obese (class I, II, and III obese; n = 97). We compared analytical and clinical data and dWOI in these categories, finding significant metabolic differences in glycemia, TSH, insulin, HDL cholesterol, LDL cholesterol, triglycerides, and systolic and diastolic blood pressure among the different BMI groups. One-day dWOI increased significantly with BMI, and significant differences were observed in the non-obese versus obese categories (9.7% vs 25.3 %, respectively (p = 0.02)). dWOI was most pronounced in patients with class II-III obesity. In addition, displacement was longer as BMI increased since ERA revealed a higher proportion of displacements of 1 day than of 12 h and showed they were predominantly pre-receptive. In conclusion, obesity has a negative effect on endometrial receptivity through delaying of the WOI, which increases in function of BMI as well as the metabolic disturbances of the patient.

17.
J Aging Soc Policy ; : 1-11, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34006195

RESUMO

This commentary focuses on the remunerated work dimension of productive aging in Mexico, specifically paid employment. The main purpose is to draw attention to productive aging policies and programs built on alliances between the Mexican government and private companies - e.g., Starbucks - and then to analyze the potential impacts of such alliances on the older population. We argue that although the Mexican government emphasizes the rights of older adults to engage in paid-employment programs through such alliances, it is not addressing the issues that underlie paid-employment activities in later life, such as conditions of inequality, lack of opportunities, and poverty. We also argue that the instrumentation of productive aging programs implemented by the government should consider the costs and benefits for older adults. Solid, research-based evidence is needed to better implement productive aging programs by accounting for the factors that influence older adults' decisions to continue working, the functional capacities of older workers, and their performance needs.

18.
Hum Reprod Open ; 2021(2): hoab011, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33880420

RESUMO

This article summarises and contextualises the accumulated basic and clinical data on the ERA test and addresses specific comments and opinions presented by the opponent as part of an invited debate. Progress in medicine depends on new technologies and concepts that translate to practice to solve long-standing problems. In a key example, combining RNA sequencing data (transcriptomics) with artificial intelligence (AI) led to a clinical revolution in personalising disease diagnosis and fostered the concept of precision medicine. The reproductive field is no exception. Translation of endometrial transcriptomics to the clinic yielded an objective definition of the limited time period during which the maternal endometrium is receptive to an embryo, known as the window of implantation (WOI). The WOI is induced by the presence of exogenous and/or endogenous progesterone (P) after proper oestradiol (E2) priming. The window lasts 30-36 hours and, depending on the patient, occurs between LH + 6 and LH + 9 in natural cycles or between P + 4 and P + 7 in hormonal replacement therapy (HRT) cycles. In approximately 30% of IVF cycles in which embryo transfer is performed blindly, the WOI is displaced and embryo-endometrial synchrony is not achieved. Extending this application of endometrial transcriptomics, the endometrial receptivity analysis (ERA) test couples next-generation sequencing (NGS) to a computational predictor to identify transcriptomic signatures for each endometrial stage: proliferative (PRO), pre-receptive (PRE), receptive (R) and post-receptive (POST). In this way, personalised embryo transfer (pET) may be possible by synchronising embryo transfer with each patient's WOI. Data are the only way to confront arguments sustained in opinions and/or misleading concepts; it is up to the reader to make their own conclusions regarding its clinical utility.

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