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  • 1
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    Table_6.xlsx
    Frontiers Media SA ; 2023
    In:  Frontiers in Endocrinology Vol. 14 ( 2023-4-19)
    Details
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 14 ( 2023-4-19)
    Abstract: Several metabolite classes have been identified in human endometrium, including lipids, nucleotides, amino acids, organic acids, and sugars. The first studies suggest the importance of metabolites in endometrial functions, as imbalance in uterine metabolites has been associated with low implantation rate and endometriosis. Nevertheless, most of studies have put emphasis on specific metabolite classes, and we lack the knowledge of the whole metabolome composition in human uterus. Further, a healthy dietary pattern has been shown to potentially protect against different endometrial dysfunctions and is a potential modulator of metabolomic composition and, consequently, the intrauterine microenvironment. The Mediterranean Diet (MD), characterized by a high intake of fruits, vegetables, cereals, nuts, legumes, fish, and olive oil, and a low consumption of meat, dairy products, and processed foods, has been associated with a wide range of benefits for health. Indeed, the MD pattern has displayed a beneficial role in endometriosis management and fertility; however, the relationship between the MD and the endometrial metabolome is still unknown. In our study, we set out to analyze receptive-phase endometrial metabolome profiles among women with infertility and their associations with MD. Methods The study included women with male factor infertility (n=8), unexplained infertility (n=10), recurrent implantation failure (n=14), and endometriosis (n=13). The endometrial metabolome was analyzed with ultrahigh-performance liquid chromatography-tandem mass spectroscopy (UPLC–MS/MS). The MD adherence of the participants was assessed using the 14-point MEDAS questionnaire of adherence to the MD. Results We provide the whole metabolome profile of the endometrium, where 925 different metabolites were identified. Among these metabolites, lipids comprised the largest part, where polyunsaturated fatty acids (PUFAs) prevailed. Women with endometriosis and recurrent implantation failure were found to have lower levels of PUFAs compared to women with male factor and unexplained infertility (i.e., no clear endometrial alterations), identifying a metabolome profile associated with infertility diagnoses where altered endometrial functions are suspected. Moreover, MD adherence seemed to be associated with the endometrial metabolomic profile in a manner dependent on the health status of the uterus. Conclusion The study findings provide insight into the molecular background of female infertility and lead to identification of potential molecular biomarkers and possibilities for modulating the endometrial microenvironment and, thereby, endometrial functions involved in embryo implantation and infertility.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fendo.2023.1120988
    DOI: 10.3389/fendo.2023.1120988.s001
    DOI: 10.3389/fendo.2023.1120988.s002
    DOI: 10.3389/fendo.2023.1120988.s003
    DOI: 10.3389/fendo.2023.1120988.s004
    DOI: 10.3389/fendo.2023.1120988.s005
    DOI: 10.3389/fendo.2023.1120988.s006
    DOI: 10.3389/fendo.2023.1120988.s007
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2592084-4
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  • 2
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    Assessing the testicular sperm microbiome: a low-biomass site with abundant contamination
    Elsevier BV ; 2021
    In:  Reproductive BioMedicine Online Vol. 43, No. 3 ( 2021-09), p. 523-531
    Details
    In: Reproductive BioMedicine Online, Elsevier BV, Vol. 43, No. 3 ( 2021-09), p. 523-531
    Type of Medium: Online Resource
    ISSN: 1472-6483
    URL: Article
    DOI: 10.1016/j.rbmo.2021.06.021
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2057455-1
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  • 3
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    A systematic review identifying seminal plasma biomarkers and their predictive ability on IVF and ICSI outcomes
    Elsevier BV ; 2024
    In:  Reproductive BioMedicine Online Vol. 48, No. 2 ( 2024-02), p. 103622-
    Details
    In: Reproductive BioMedicine Online, Elsevier BV, Vol. 48, No. 2 ( 2024-02), p. 103622-
    Type of Medium: Online Resource
    ISSN: 1472-6483
    URL: Article
    DOI: 10.1016/j.rbmo.2023.103622
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
    detail.hit.zdb_id: 2057455-1
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  • 4
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    FUNCTIONALLY ACTIVE MICROBIOTA LANDSCAPE IN RECURRENT IMPLANTATION FAILURE
    Elsevier BV ; 2022
    In:  Fertility and Sterility Vol. 118, No. 4 ( 2022-10), p. e344-
    Details
    In: Fertility and Sterility, Elsevier BV, Vol. 118, No. 4 ( 2022-10), p. e344-
    Type of Medium: Online Resource
    ISSN: 0015-0282
    URL: Article
    DOI: 10.1016/j.fertnstert.2022.09.141
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 1500469-7
    SSG: 12
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  • 5
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    Omission of non-poly(A) viral transcripts from the tissue level atlas of the healthy human virome
    Springer Science and Business Media LLC ; 2020
    In:  BMC Biology Vol. 18, No. 1 ( 2020-12)
    Details
    In: BMC Biology, Springer Science and Business Media LLC, Vol. 18, No. 1 ( 2020-12)
    Abstract: A recent paper in BMC Biology entitled “A tissue level atlas of the healthy human virome” by Kumata et al. describes a meta-transcriptomic analysis of RNA-sequencing datasets from the Genotype-Tissue Expression (GTEx) Project. Using a workflow that maps the GTEx sequences to the human genome, then screens unmapped sequences to detect viral transcripts, the authors present a quantitative analysis of the presence of different viruses in the non-diseased tissues of over 500 individuals and assess the impact of these viruses on host gene expression. Here we draw attention to an issue not acknowledged in this study. Namely, by relying solely on GTEx datasets, which are enriched for transcripts with poly(A) tails, the analysis will have missed non-poly(A) viral transcripts, rendering this tissue level atlas of the virome incomplete. A commentary on Kumata et al. (BMC Biol 18:55, 2020).
    Type of Medium: Online Resource
    ISSN: 1741-7007
    URL: Article
    DOI: 10.1186/s12915-020-00907-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2133020-7
    SSG: 12
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  • 6
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    Analysing endometrial microbiome: methodological considerations and recommendations for good practice
    Oxford University Press (OUP) ; 2021
    In:  Human Reproduction Vol. 36, No. 4 ( 2021-03-18), p. 859-879
    Details
    In: Human Reproduction, Oxford University Press (OUP), Vol. 36, No. 4 ( 2021-03-18), p. 859-879
    Abstract: There is growing evidence that the upper female genital tract is not sterile, harbouring its own microbial communities. However, the significance and the potential effect of endometrial microorganisms on reproductive functions remain to be fully elucidated. Analysing the endometrial microbiome, the microbes and their genetic material present in the endometrium, is an emerging area of study. The initial studies suggest it is associated with poor reproductive outcomes and with different gynaecological pathologies. Nevertheless, studying a low-biomass microbial niche as is endometrium, the challenge is to conduct well-designed and well-controlled experiments in order to avoid and adjust for the risk of contamination, especially from the lower genital tract. Herein, we aim to highlight methodological considerations and propose good practice recommendations for future endometrial microbiome studies.
    Type of Medium: Online Resource
    ISSN: 0268-1161 , 1460-2350
    URL: Article
    DOI: 10.1093/humrep/deab009
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1484864-8
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  • 7
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    Microbial composition across body sites in polycystic ovary syndrome: a systematic review and meta-analysis
    Elsevier BV ; 2023
    In:  Reproductive BioMedicine Online Vol. 47, No. 1 ( 2023-07), p. 129-150
    Details
    In: Reproductive BioMedicine Online, Elsevier BV, Vol. 47, No. 1 ( 2023-07), p. 129-150
    Type of Medium: Online Resource
    ISSN: 1472-6483
    URL: Article
    DOI: 10.1016/j.rbmo.2023.03.016
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2057455-1
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  • 8
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    Mapping the entire functionally active endometrial microbiota
    Oxford University Press (OUP) ; 2021
    In:  Human Reproduction Vol. 36, No. 4 ( 2021-03-18), p. 1021-1031
    Details
    In: Human Reproduction, Oxford University Press (OUP), Vol. 36, No. 4 ( 2021-03-18), p. 1021-1031
    Abstract: Does endometrium harbour functionally active microorganisms and whether the microbial composition differs between proliferative and mid-secretory phases? SUMMARY ANSWER Endometrium harbours functionally alive microorganisms including bacteria, viruses, archaea and fungi whose composition and metabolic functions change along the menstrual cycle. WHAT IS KNOWN ALREADY Resident microbes in the endometrium have been detected, where microbial dysfunction has been associated with reproductive health and disease. Nevertheless, the core microorganismal composition in healthy endometrium is not determined and whether the identified bacterial DNA sequences refer to alive/functionally active microbes is not clear. Furthermore, whether there are cyclical changes in the microbial composition remains an open issue. STUDY DESIGN, SIZE, DURATION RNA sequencing (RNAseq) data from 14 endometrial paired samples from healthy women, 7 samples from the mid-secretory phase and 7 samples from the consecutive proliferative phase were analysed for the microbial RNA sequences. PARTICIPANTS/MATERIALS, SETTING, METHODS The raw RNAseq data were converted into FASTQ format using SRA Toolkit. The unmapped reads to human sequences were aligned to the reference database Kraken2 and visualised with Krona software. Menstrual phase taxonomic differences were performed by R package metagenomeSeq. The functional analysis of endometrial microbiota was obtained with HUMANn2 and the comparison between menstrual phases was conducted by one-way ANOVA. Human RNAseq analysis was performed using miARma-Seq and the functional enrichment analysis was carried out using gene set enrichment analysis (GSEA; HumanCyc). The integration of metabolic pathways between host and microbes was investigated. The developed method of active microbiota mapping was validated in independent sample set. MAIN RESULTS AND THE ROLE OF CHANCE With the novel metatranscriptomic approach, we mapped the entire alive microbiota composing of & gt;5300 microorganisms within the endometrium of healthy women. Microbes such as bacteria, fungi, viruses and archaea were identified. The validation of three independent endometrial samples from different ethnicity confirmed the findings. Significant differences in the microbial abundances in the mid-secretory vs. proliferative phases were detected with possible metabolic activity in the host-microbiota crosstalk in receptive phase endometrium, specifically in the prostanoid biosynthesis pathway and L-tryptophan metabolism. LARGE SCALE DATA The raw RNAseq data used in the current study are available at GEO GSE86491 and at BioProject PRJNA379542. LIMITATIONS, REASONS FOR CAUTION These pioneering results should be confirmed in a bigger sample size. WIDER IMPLICATIONS OF THE FINDINGS Our study confirms the presence of active microbes, bacteria, fungi, viruses and archaea in the healthy human endometrium with implications in receptive phase endometrial functions, meaning that microbial dysfunction could impair the metabolic pathways important for endometrial receptivity. The results of this study contribute to the better understanding of endometrial microbiota composition in healthy women and its possible role in endometrial functions. In addition, our novel methodological pipeline for analysing alive microbes with transcriptional and metabolic activities could serve to inspire new analysis approaches in reproductive medicine. STUDY FUNDING/COMPETING INTERESTS This work is supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and European Regional Development Fund (FEDER): grants RYC-2016-21199 and ENDORE SAF2017-87526-R; FEDER/Junta de Andalucía-Consejería de Economía y Conocimiento: MENDO (B-CTS-500-UGR18) and by the University of Granada Plan Propio de Investigación 2016 - Excellence actions: Unit of Excellence on Exercise and Health (UCEES) (SOMM17/6107/UGR). A.S.-L. and N.M.M. are funded by the Spanish Ministry of Science, Innovation and Universities (PRE2018-0854409 and FPU19/01638). S.A. has received honoraria for lectures from Merck. The funder had no role in this study.
    Type of Medium: Online Resource
    ISSN: 0268-1161 , 1460-2350
    URL: Article
    DOI: 10.1093/humrep/deaa372
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1484864-8
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  • 9
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    The Gut Microbiome in Polycystic Ovary Syndrome and Its Association with Metabolic Traits
    The Endocrine Society ; 2021
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 106, No. 3 ( 2021-03-08), p. 858-871
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 106, No. 3 ( 2021-03-08), p. 858-871
    Abstract: Despite the gut microbiome being widely studied in metabolic diseases, its role in polycystic ovary syndrome (PCOS) has been scarcely investigated. Objective Compare the gut microbiome in late fertile age women with and without PCOS and investigate whether changes in the gut microbiome correlate with PCOS-related metabolic parameters. Design Prospective, case–control study using the Northern Finland Birth Cohort 1966. Setting General community. Participants A total of 102 PCOS women and 201 age- and body mass index (BMI)-matched non-PCOS control women. Clinical and biochemical characteristics of the participants were assessed at ages 31 and 46 and analyzed in the context of gut microbiome data at the age of 46. Intervention (s): None Main outcome measure(s) Bacterial diversity, relative abundance, and correlations with PCOS-related metabolic measures. Results Bacterial diversity indices did not differ significantly between PCOS and controls (Shannon diversity P = .979, unweighted UniFrac P = .175). Four genera whose balance helps to differentiate between PCOS and non-PCOS were identified. In the whole cohort, the abundance of 2 genera from Clostridiales, Ruminococcaceae UCG-002, and Clostridiales Family XIII AD3011 group, were correlated with several PCOS-related markers. Prediabetic PCOS women had significantly lower alpha diversity (Shannon diversity P = .018) and markedly increased abundance of genus Dorea (false discovery rate = 0.03) compared with women with normal glucose tolerance. Conclusion PCOS and non-PCOS women at late fertile age with similar BMI do not significantly differ in their gut microbial profiles. However, there are significant microbial changes in PCOS individuals depending on their metabolic health.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgaa848
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2026217-6
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  • 10
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    Effect of Direct Transportation to Thrombectomy-Capable Center vs Local Stroke Center on Neurological Outcomes in Patients With Suspected Large-Vessel Occlusion Stroke in Nonurban Areas : The RACECAT Randomized Clinical Trial
    American Medical Association (AMA) ; 2022
    In:  JAMA Vol. 327, No. 18 ( 2022-05-10), p. 1782-
    Details
    In: JAMA, American Medical Association (AMA), Vol. 327, No. 18 ( 2022-05-10), p. 1782-
    Abstract: In nonurban areas with limited access to thrombectomy-capable centers, optimal prehospital transport strategies in patients with suspected large-vessel occlusion stroke are unknown. Objective To determine whether, in nonurban areas, direct transport to a thrombectomy-capable center is beneficial compared with transport to the closest local stroke center. Design, Setting, and Participants Multicenter, population-based, cluster-randomized trial including 1401 patients with suspected acute large-vessel occlusion stroke attended by emergency medical services in areas where the closest local stroke center was not capable of performing thrombectomy in Catalonia, Spain, between March 2017 and June 2020. The date of final follow-up was September 2020. Interventions Transportation to a thrombectomy-capable center (n = 688) or the closest local stroke center (n = 713). Main Outcomes and Measures The primary outcome was disability at 90 days based on the modified Rankin Scale (mRS; scores range from 0 [no symptoms] to 6 [death] ) in the target population of patients with ischemic stroke. There were 11 secondary outcomes, including rate of intravenous tissue plasminogen activator administration and thrombectomy in the target population and 90-day mortality in the safety population of all randomized patients. Results Enrollment was halted for futility following a second interim analysis. The 1401 enrolled patients were included in the safety analysis, of whom 1369 (98%) consented to participate and were included in the as-randomized analysis (56% men; median age, 75 [IQR, 65-83] years; median National Institutes of Health Stroke Scale score, 17 [IQR, 11-21] ); 949 (69%) comprised the target ischemic stroke population included in the primary analysis. For the primary outcome in the target population, median mRS score was 3 (IQR, 2-5) vs 3 (IQR, 2-5) (adjusted common odds ratio [OR], 1.03; 95% CI, 0.82-1.29). Of 11 reported secondary outcomes, 8 showed no significant difference. Compared with patients first transported to local stroke centers, patients directly transported to thrombectomy-capable centers had significantly lower odds of receiving intravenous tissue plasminogen activator (in the target population, 229/482 [47.5%] vs 282/467 [60.4%]; OR, 0.59; 95% CI, 0.45-0.76) and significantly higher odds of receiving thrombectomy (in the target population, 235/482 [48.8%] vs 184/467 [39.4%]; OR, 1.46; 95% CI, 1.13-1.89). Mortality at 90 days in the safety population was not significantly different between groups (188/688 [27.3%] vs 194/713 [27.2%]; adjusted hazard ratio, 0.97; 95% CI, 0.79-1.18). Conclusions and Relevance In nonurban areas in Catalonia, Spain, there was no significant difference in 90-day neurological outcomes between transportation to a local stroke center vs a thrombectomy-capable referral center in patients with suspected large-vessel occlusion stroke. These findings require replication in other settings. Trial Registration ClinicalTrials.gov Identifier: NCT02795962
    Type of Medium: Online Resource
    ISSN: 0098-7484
    URL: Article
    DOI: 10.1001/jama.2022.4404
    RVK:
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    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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