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BACKGROUND: The effects of physical activity and sedentary behavior on human health are well known, however, the molecular mechanisms are poorly understood. Growing evidence points to physical activity as an important modulator of the composition and function of microbial communities, while evidence of sedentary behavior is scarce. We aimed to synthesize and meta-analyze the current evidence about the effects of physical activity and sedentary behavior on microbiome across different body sites and in different populations. METHODS: A systematic search in PubMed, Web of Science, Scopus and Cochrane databases was conducted until September 2022. Random-effects meta-analyses including cross-sectional studies (active vs. inactive/athletes vs. non-athletes) or trials reporting the chronic effect of physical activity interventions on gut microbiome alpha-diversity in healthy individuals were performed. RESULTS: Ninety-one studies were included in this systematic review. Our meta-analyses of 2632 participants indicated no consistent effect of physical activity on microbial alpha-diversity, although there seems to be a trend toward a higher microbial richness in athletes compared to non-athletes. Most of studies reported an increase in short-chain fatty acid-producing bacteria such as Akkermansia, Faecalibacterium, Veillonella or Roseburia in active individuals and after physical activity interventions. CONCLUSIONS: Physical activity levels were positively associated with the relative abundance of short-chain fatty acid-producing bacteria. Athletes seem to have a richer microbiome compared to non-athletes. However, high heterogeneity between studies avoids obtaining conclusive information on the role of physical activity in microbial composition. Future multi-omics studies would enhance our understanding of the molecular effects of physical activity and sedentary behavior on the microbiome.
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The beneficial effects of physical activity (PA) on gut microbiome have been reported, nevertheless the findings are inconsistent, with the main limitation of subjective methods for assessing PA. It is well accepted that using an objective assessment of PA reduces the measurement error and also allows objective assessment of sedentary behavior (SB). We aimed to study the associations between accelerometer-assessed behaviors (i.e., SB, light-intensity physical activity [LPA] and moderate-to-vigorous physical activity [MVPA]) with the gut microbiome using compositional data analysis, a novel approach that enables to study these behaviors accounting for their inter-dependency. This cross-sectional study included 289 women from the Northern Finland Birth Cohort 1966. Physical activity was measured during 14 days by wrist-worn accelerometers. Analyses based on the combined effect of MVPA and SB, and compositional data analyses in association with the gut microbiome data were performed. The microbial alpha- and beta-diversity were not significantly different between the MVPA-SB groups, and no differentially abundant microorganisms were detected. Compositional data analysis did not show any significant associations between any movement behavior (relative to the others) on microbial alpha-diversity. Butyrate-producing bacteria such as Agathobacter and Lachnospiraceae CAG56 were significantly more abundant when reallocating time from LPA or SB to MVPA (γ = 0.609 and 0.113, both p-values = 0.007). While PA and SB were not associated with microbial diversity, we found associations of these behaviors with specific gut bacteria, suggesting that PA of at least moderate intensity (i.e., MVPA) could increase the abundance of short-chain fatty acid-producing microbes.
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Acelerometría , Ejercicio Físico , Microbioma Gastrointestinal , Conducta Sedentaria , Humanos , Femenino , Microbioma Gastrointestinal/fisiología , Estudios Transversales , Ejercicio Físico/fisiología , Persona de Mediana Edad , FinlandiaRESUMEN
BACKGROUND: Endometriosis, defined as the presence of endometrial-like tissue outside of the uterus, is one of the most prevalent gynecological disorders. Although different theories have been proposed, its pathogenesis is not clear. Novel studies indicate that the gut microbiome may be involved in the etiology of endometriosis; nevertheless, the connection between microbes, their dysbiosis, and the development of endometriosis is understudied. This case-control study analyzed the gut microbiome in women with and without endometriosis to identify microbial targets involved in the disease. METHODS: A subsample of 1000 women from the Estonian Microbiome cohort, including 136 women with endometriosis and 864 control women, was analyzed. Microbial composition was determined by shotgun metagenomics and microbial functional pathways were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Partitioning Around Medoids (PAM) algorithm was performed to cluster the microbial profile of the Estonian population. The alpha- and beta-diversity and differential abundance analyses were performed to assess the gut microbiome (species and KEGG orthologies (KO)) in both groups. Metagenomic reads were mapped to estrobolome-related enzymes' sequences to study potential microbiome-estrogen metabolism axis alterations in endometriosis. RESULTS: Diversity analyses did not detect significant differences between women with and without endometriosis (alpha-diversity: all p-values > 0.05; beta-diversity: PERMANOVA, both R 2 < 0.0007, p-values > 0.05). No differential species or pathways were detected after multiple testing adjustment (all FDR p-values > 0.05). Sensitivity analysis excluding women at menopause (> 50 years) confirmed our results. Estrobolome-associated enzymes' sequence reads were not significantly different between groups (all FDR p-values > 0.05). CONCLUSIONS: Our findings do not provide enough evidence to support the existence of a gut microbiome-dependent mechanism directly implicated in the pathogenesis of endometriosis. To the best of our knowledge, this is the largest metagenome study on endometriosis conducted to date.
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Endometriosis , Microbioma Gastrointestinal , Humanos , Endometriosis/microbiología , Femenino , Microbioma Gastrointestinal/fisiología , Adulto , Estudios de Casos y Controles , Estonia/epidemiología , Estudios de Cohortes , Persona de Mediana Edad , Metagenómica , Disbiosis/microbiología , Adulto JovenRESUMEN
PURPOSE OF REVIEW: The analysis of microbiome in association with female health is today a "hot topic" with the main focus on microbes in the female reproductive tract. Nevertheless, recent studies are providing novel information of the possible influence of the gut microbiome on gynecological health outcomes, especially as we start to understand that the gut microbiome is an extended endocrine organ influencing female hormonal levels. This review summarizes the current knowledge of the gut microbes in association with gynecological health. RECENT FINDINGS: The gut microbiome has been associated with endometriosis, polycystic ovary syndrome, gynecological cancers, and infertility, although there is a lack of consistency and consensus among studies due to different study designs and protocols used, and the studies in general are underpowered. SUMMARY: The interconnection between the gut microbiome and reproductive health is complex and further research is warranted. The current knowledge in the field emphasizes the link between the microbiome and gynecological health outcomes, with high potential for novel diagnostic and treatment tools via modulation of the microenvironment.
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Endometriosis , Microbioma Gastrointestinal , Síndrome del Ovario Poliquístico , Salud Reproductiva , Humanos , Femenino , Microbioma Gastrointestinal/fisiología , Endometriosis/microbiología , Síndrome del Ovario Poliquístico/microbiología , Genitales Femeninos/microbiología , Neoplasias de los Genitales Femeninos/microbiología , Infertilidad Femenina/microbiología , Enfermedades de los Genitales Femeninos/microbiologíaRESUMEN
BACKGROUND: The increasing prevalence of obesity worldwide poses a significant threat to reproductive function owing, in part, to hormonal disturbances caused by negative feedback between excess adiposity and the hypothalamic-pituitary-ovarian axis. Consequently, finding the most appropriate strategies to lose weight and improve ovulation in women with overweight or obesity is a clinically relevant matter that needs to be investigated. A comprehensive comparison of the independent and combined efficacy of lifestyle and/or pharmacological interventions on BMI, ovulation, and hormonal profile in women with overweight or obesity at risk of anovulatory infertility would facilitate improving fertility strategies in this population. OBJECTIVE AND RATIONALE: This study aimed to evaluate the comparative efficacy of exercise, diet, and pharmacological interventions on BMI, ovulation, and hormonal profile in reproductive-aged women with overweight or obesity. SEARCH METHODS: A systematic review was performed by searching PubMed, Scopus, Web of Science, PsycINFO, and Cochrane Library up to 14 December 2023, for randomized controlled trials assessing the effects of exercise, diet and/or pharmacological interventions (i.e. weight-lowering drugs or ovulation inducers) on BMI, ovulation, and/or hormonal profile in reproductive-aged women with overweight or obesity. We performed frequentist random-effect network meta-analyses and rated the certainty of the evidence. The primary outcomes were BMI and ovulation rate, and the secondary outcomes were serum reproductive hormone levels (gonadotrophins, androgens, or oestrogens). We performed sensitivity analyses, including the studies that only involved women with PCOS. OUTCOMES: Among 1190 records screened, 148 full texts were assessed for eligibility resulting in 95 trials (9910 women), of which 53% presented a high or unclear risk of bias. The network meta-analyses revealed that, compared to control: diet combined with weight-lowering drugs (mean difference (MD) -2.61 kg/m2; 95% CI -3.04 to -2.19; τ2 = 0.22) and adding exercise (MD -2.35 kg/m2; 95% CI -2.81 to -1.89; τ2 = 0.22) led to the greatest decrease in BMI; exercise combined with diet and ovulation inducers (risk ratio (RR) 7.15; 95% CI 1.94-26.40; τ2 = 0.07) and exercise combined with diet and weight-lowering drugs (RR 4.80; 95% CI 1.67-13.84; τ2 = 0.07) produced the highest increase in ovulation rate; and exercise combined with diet and weight-lowering drugs was the most effective strategy in reducing testosterone levels (standardized mean difference (SMD) -2.91; 95% CI -4.07 to -1.74; τ2 = 2.25), the third most effective strategy in increasing sex hormone-binding globulin levels (SMD 2.37; 95% CI 0.99-3.76; τ2 = 2.48), and it was coupled with being ranked first in terms of free androgen index reduction (SMD -1.59; 95% CI -3.18 to 0.01; τ2 = 1.91). The surface under the cumulative ranking curve scores suggested that: diet combined with weight-lowering drugs is the strategy most likely (94%) to produce the highest BMI reduction; and exercise combined with diet and ovulation inducers is the strategy most likely (89%) to produce the highest ovulation rate improvement. The sensitivity analyses, which exclusively included studies involving women diagnosed with PCOS, were consistent with the results presented above. WIDER IMPLICATIONS: Overall, the findings of this network meta-analysis indicate that the combination of exercise, diet, and pharmacological interventions is effective for weight loss, improving ovulation, and normalizing the androgen levels of women with overweight or obesity. Although higher quality studies are needed, these results support that the optimal treatment strategy for women with overweight or obesity wishing to conceive must consider exercise, diet, and pharmacological interventions during the shared decision-making process.
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Índice de Masa Corporal , Ejercicio Físico , Obesidad , Sobrepeso , Ovulación , Adulto , Femenino , Humanos , Dieta , Metaanálisis en Red , Obesidad/dietoterapia , Obesidad/terapia , Obesidad/complicaciones , Obesidad/sangre , Sobrepeso/terapia , Sobrepeso/dietoterapia , Sobrepeso/complicaciones , Sobrepeso/sangre , Ovulación/efectos de los fármacosRESUMEN
PURPOSE OF REVIEW: The analysis of microbiome in association with female health is today a "hot topic" with the main focus on microbes in the female reproductive tract. Nevertheless, recent studies are providing novel information of the possible influence of the gut microbiome on gynecological health outcomes, especially as we start to understand that the gut microbiome is an extended endocrine organ influencing female hormonal levels. This review summarizes the current knowledge of the gut microbes in association with gynecological health. RECENT FINDINGS: The gut microbiome has been associated with endometriosis, polycystic ovary syndrome, gynecological cancers, and infertility, although there is a lack of consistency and consensus among studies due to different study designs and protocols used, and the studies in general are underpowered. SUMMARY: The interconnection between the gut microbiome and reproductive health is complex and further research is warranted. The current knowledge in the field emphasizes the link between the microbiome and gynecological health outcomes, with high potential for novel diagnostic and treatment tools via modulation of the microenvironment.
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INTRODUCTION: Implantation failure after transferring morphologically "good-quality" embryos in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) may be explained by impaired endometrial receptivity. Analyzing the endometrial transcriptome analysis may reveal the underlying processes and could help in guiding prognosis and using targeted interventions for infertility. This exploratory study investigated whether the endometrial transcriptome profile was associated with short-term or long-term implantation outcomes (ie success or failure). MATERIAL AND METHODS: Mid-luteal phase endometrial biopsies of 107 infertile women with one full failed IVF/ICSI cycle, obtained within an endometrial scratching trial, were subjected to RNA-sequencing and differentially expressed genes analysis with covariate adjustment (age, body mass index, luteinizing hormone [LH]-day). Endometrial transcriptomes were compared between implantation failure and success groups in the short term (after the second fresh IVF/ICSI cycle) and long term (including all fresh and frozen cycles within 12 months). The short-term analysis included 85/107 women (33 ongoing pregnancy vs 52 no pregnancy), excluding 22/107 women. The long-term analysis included 46/107 women (23 'fertile' group, ie infertile women with a live birth after ≤3 embryos transferred vs 23 recurrent implantation failure group, ie no live birth after ≥3 good quality embryos transferred), excluding 61/107 women not fitting these categories. As both analyses drew from the same pool of 107 samples, there was some sample overlap. Additionally, cell type enrichment scores and endometrial receptivity were analyzed, and an endometrial development pseudo-timeline was constructed to estimate transcriptomic deviations from the optimum receptivity day (LH + 7), denoted as ΔWOI (window of implantation). RESULTS: There were no significantly differentially expressed genes between implantation failure and success groups in either the short-term or long-term analyses. Principal component analysis initially showed two clusters in the long-term analysis, unrelated to clinical phenotype and no longer distinct following covariate adjustment. Cell type enrichment scores did not differ significantly between groups in both analyses. However, endometrial receptivity analysis demonstrated a potentially significant displacement of the WOI in the non-pregnant group compared with the ongoing pregnant group in the short-term analysis. CONCLUSIONS: No distinct endometrial transcriptome profile was associated with either implantation failure or success in infertile women. However, there may be differences in the extent to which the WOI is displaced.
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Implantación del Embrión , Endometrio , Infertilidad Femenina , Transcriptoma , Humanos , Femenino , Infertilidad Femenina/genética , Infertilidad Femenina/terapia , Infertilidad Femenina/metabolismo , Endometrio/metabolismo , Adulto , Embarazo , Inyecciones de Esperma Intracitoplasmáticas , Transferencia de Embrión , Fertilización In VitroRESUMEN
A frequent finding after preimplantation genetic diagnostic testing for aneuploidies using next-generation sequencing is an embryo that is putatively mosaic. The prevalence of this outcome remains unclear and varies with technical and external factors. Mosaic embryos can be classified by the percentage of cells affected, type of chromosome involvement (whole or segmental), number of affected chromosomes or affected cell type (inner mass cell, trophectoderm or both). The origin of mosaicism seems to be intrinsic as a post-zygotic mitotic error, but some external factors can play a role. As experience has increased with the transfer of mosaic embryos, clinical practice has gradually become more flexible in recent years. Nevertheless, clinical results show lower implantation, pregnancy and clinical pregnancy rates and higher miscarriage rates with mosaic embryo transfer when compared with the transfer of euploid embryos. Prenatal diagnosis is highly recommended after the transfer of mosaic embryos. This narrative review is intended to serve as reference material for practitioners in reproductive medicine who must manage a mosaic embryo result after preimplantation genetic testing for aneuploidies.
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Diagnóstico Preimplantación , Embarazo , Femenino , Humanos , Diagnóstico Preimplantación/métodos , Pruebas Genéticas/métodos , Implantación del Embrión , Aneuploidia , Mosaicismo , Blastocisto/metabolismoRESUMEN
BACKGROUND: The current knowledge about the molecular mechanisms underlying the health benefits of exercise is still limited, especially in childhood. We set out to investigate the effects of a 20-week exercise intervention on whole-blood transcriptome profile (RNA-seq) in children with overweight/obesity. METHODS: Twenty-four children (10.21 ± 1.33 years, 46% girls) with overweight/obesity, were randomized to either a 20-week exercise program (intervention group; n = 10), or to a no-exercise control group (n = 14). Whole-blood transcriptome profile was analyzed using RNA-seq by STRT technique with GlobinLock technology. RESULTS: Following the 20-week exercise intervention program, 161 genes were differentially expressed between the exercise and the control groups among boys, and 121 genes among girls (p-value <0.05), while after multiple correction, no significant difference between exercise and control groups persisted in gene expression profiles (FDR >0.05). Genes enriched in GO processes and molecular pathways showed different immune response in boys (antigen processing and presentation, infections, and T cell receptor complex) and in girls (Fc epsilon RI signaling pathway) (FDR <0.05). CONCLUSION: These results suggest that 20-week exercise intervention program alters the molecular pathways involved in immune processes in children with overweight/obesity.
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Sobrepeso , Transcriptoma , Masculino , Niño , Femenino , Humanos , Sobrepeso/genética , Sobrepeso/terapia , Obesidad/genética , Ejercicio Físico/fisiologíaRESUMEN
Infertility is a complex condition affecting millions of couples worldwide. The current definition of infertility, based on clinical criteria, fails to account for the molecular and cellular changes that may occur during the development of infertility. Recent advancements in sequencing technology and single-cell analysis offer new opportunities to gain a deeper understanding of these changes. The endometrium has a potential role in infertility and has been extensively studied to identify gene expression profiles associated with (impaired) endometrial receptivity. However, limited overlap among studies hampers the identification of relevant downstream pathways that could play a role in the development of endometrial-related infertility. To address these challenges, we propose sequencing the endometrial transcriptome of healthy and infertile women at the single-cell level to consistently identify molecular signatures. Establishing consensus on physiological patterns in endometrial samples can aid in identifying deviations in infertile patients. A similar strategy has been used with great success in cancer research. However, large collaborative initiatives, international uniform protocols of sample collection and processing are crucial to ensure reliability and reproducibility. Overall, the proposed approach holds promise for an objective and accurate classification of endometrial-based infertility and has the potential to improve diagnosis and treatment outcomes.
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Infertilidad Femenina , Femenino , Humanos , Infertilidad Femenina/diagnóstico , Infertilidad Femenina/genética , Infertilidad Femenina/metabolismo , Reproducibilidad de los Resultados , Endometrio/metabolismo , Transcriptoma , Resultado del Tratamiento , Implantación del Embrión/fisiologíaRESUMEN
The diverse nature and high molecule concentration of seminal plasma (SP) makes this fluid a good potential source for a potential biomarker that could predict assisted reproductive technology (ART) outcomes. Currently, semen quality parameters cannot accurately predict ART outcomes. A systematic literature search was conducted to identify human SP biomarkers with potential predictive ability for the outcomes of IVF and intracytoplasmic sperm injection. Observational cohort and case-control studies describing the association between biomarkers in human SP and the outcome of infertile men attending for ART were included. Forty-three studies were selected, reporting on 89 potential SP biomarkers (grouped as oxidative stress, proteins glycoproteins, metabolites, immune system components, metals and trace elements and nucleic acids). The present review supports 32 molecules in SP as potentially relevant biomarkers for predicting ART outcomes; 23 molecules were reported once and nine molecules were reported in more than one study; IL-18 and TGF-ß1-IL-18 ratio were confirmed in distinct studies. This review presents the most comprehensive overview of relevant SP biomarkers to predict ART outcomes to date, which is of clinical interest for infertility investigations and assisted reproduction; nevertheless, its potential is under-exploited. This review could serve as starting point for designing an all-encompassing study for biomarkers in SP and their predictive ability for ART outcomes, and for developing a non-invasive diagnostic tool.
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Infertilidad , Inyecciones de Esperma Intracitoplasmáticas , Femenino , Humanos , Masculino , Embarazo , Biomarcadores/metabolismo , Fertilización In Vitro , Infertilidad/metabolismo , Interleucina-18/metabolismo , Índice de Embarazo , Técnicas Reproductivas Asistidas , Semen/metabolismo , Análisis de SemenRESUMEN
We investigated the interaction between a genetic score and an exercise intervention on brain health in children with overweight/obesity. One hundred one children with overweight/obesity (10.0 ± 1.5 yr, 59% girls) were randomized into a 20-wk combined exercise intervention or a control group. Several cognitive and academic outcomes were measured with validated tests. Hippocampal volume was quantified using magnetic resonance imaging. Six brain health-related polymorphisms [rs6265 (BDNF), rs2253206 (CREB1), rs2289656 (NTRK2), rs4680 (COMT), rs429358, and rs7412 (APOE)] were genotyped. Cognitive flexibility and academic skills improved significantly more in the exercise than in the control group only in the children with a "favorable" genetic profile [mean z-score, 0.41-0.67 (95% CI 0.11 to 1.18)], yet not in those with "less favorable" genetic profile. An individual response analysis showed that children responded to exercise in cognitive flexibility only in the "genetically favorable" group [i.e., 62% of them had a meaningful (≥0.2 Cohen d) increase in the exercise group compared with only 25% in the control group]. This finding was consistent in per-protocol and intention-to-treat analyses (P = 0.01 and P = 0.03, respectively). The results were not significant or not consistent for the rest of outcomes studied. Our findings suggest that having a more favorable genetic profile makes children with overweight/obesity more responsive to exercise, particularly for cognitive flexibility.NEW & NOTEWORTHY Interindividual differences have been reported in brain health-related outcomes in response to exercise interventions in adults, which could be partially explained by genetic background differences. However, the role of genetic polymorphisms on brain health-related outcomes in response to exercise interventions remains unexplored in pediatric population. The current study in children with overweight/obesity showed that a genetic score composed of six brain health-related polymorphisms (BDNF, CREB1, NTRK2, COMT, and APOE) regulated the exercise-induced response on several brain health outcomes, yet mainly and more consistently on cognitive flexibility.
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Factor Neurotrófico Derivado del Encéfalo , Sobrepeso , Femenino , Adulto , Humanos , Niño , Masculino , Sobrepeso/genética , Factor Neurotrófico Derivado del Encéfalo/genética , Obesidad/genética , Encéfalo , Apolipoproteínas ERESUMEN
Introduction: The female reproductive tract harbours unique microbial communities (known as microbiota) which have been associated with reproductive functions in health and disease. While endometrial microbiome studies have shown that the uterus possesses higher bacterial diversity and richness compared to the vagina, the knowledge regarding the composition of the Fallopian tubes (FT) is lacking, especially in fertile women without any underlying conditions. Methods: To address this gap, our study included 19 patients who underwent abdominal hysterectomy for benign uterine pathology, and 5 women who underwent tubal ligation as a permanent contraceptive method at Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA). We analyzed the microbiome of samples collected from the FT and endometrium using 16S rRNA gene sequencing. Results: Our findings revealed distinct microbiome profiles in the endometrial and FT samples, indicating that the upper reproductive tract harbors an endogenous microbiome. However, these two sites also shared some similarities, with 69% of the detected taxa Being common to both. Interestingly, we identified seventeen bacterial taxa exclusively present in the FT samples, including the genera Enhydrobacter, Granulicatella, Haemophilus, Rhizobium, Alistipes, and Paracoccus, among others. On the other hand, 10 bacterial taxa were only found in the endometrium, including the genera Klebsiella, Olsenella, Oscillibacter and Veillonella (FDR <0.05). Furthermore, our study highlighted the influence of the endometrial collection method on the findings. Samples obtained transcervically showed a dominance of the genus Lactobacillus, which may indicate potential vaginal contamination. In contrast, uterine samples obtained through hysterescopy revealed higher abundance of the genera Acinetobacter, Arthrobacter, Coprococcus, Methylobacterium, Prevotella, Roseburia, Staphylococcus, and Streptococcus. Discussion: Although the upper reproductive tract appears to have a low microbial biomass, our results suggest that the endometrial and FT microbiome is unique to each individual. In fact, samples obtained from the same individual showed more microbial similarity between the endometrium and FT compared to samples from different women. Understanding the composition of the female upper reproductive microbiome provides valuable insights into the natural microenvironment where processes such as oocyte fertilization, embryo development and implantation occur. This knowledge can improve in vitro fertilization and embryo culture conditions for the treatment of infertility.
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Infertilidad , Útero , Femenino , Humanos , ARN Ribosómico 16S/genética , Endometrio , Vagina/microbiología , Bacterias/genéticaRESUMEN
Introduction: 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.
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Dieta Mediterránea , Endometriosis , Infertilidad Femenina , Animales , Femenino , Humanos , Masculino , Endometriosis/complicaciones , Cromatografía Liquida , Espectrometría de Masas en Tándem , Endometrio/metabolismo , Infertilidad Femenina/metabolismo , Metaboloma , LípidosRESUMEN
Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting reproductive-aged women, but the cause remains unclear. Recent evidence has linked microbial composition with PCOS; however, the results are inconsistent. The aim of this systematic review was to gather current knowledge of the microbes across body sites (oral cavity, blood, vagina/cervix, gut) in women with PCOS, and meta-analyse the microbial diversity in PCOS. For this purpose, a systematic search using PubMed, Web of Science, Cochrane and Scopus was carried out. After selection, 34 studies met the inclusion criteria. Most of the studies associated changes in the microbiome with PCOS, whereas heterogeneity of the studies in terms of ethnicity, body mass index (BMI) and methodology, among other confounders, made it difficult to corroborate this relationship. In fact, 19 out of 34 of the studies were categorised as having high risk of bias when the quality assessment was conducted. Our meta-analysis on the gut microbiome of 14 studies demonstrated that women with PCOS possess significantly lower microbial alpha diversity compared with controls (SMDâ¯=â¯-0.204; 95% CI -0.360 to -0.048; Pâ¯=â¯0.010; I2â¯=â¯5.508, by Shannon Index), which may contribute to the development of PCOS. Nevertheless, future studies should specifically overcome the shortcomings of the current studies by through well planned and conducted studies with larger sample sizes, proper negative and positive controls and adequate case-control matching.
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Síndrome del Ovario Poliquístico , Humanos , Femenino , Adulto , Índice de Masa Corporal , PubMed , ReproducciónRESUMEN
The generative pre-trained transformer, ChatGPT, is a chatbot that could serve as a powerful tool in scientific writing. ChatGPT is a so-called large language model (LLM) that is trained to mimic the statistical patterns of language in an enormous database of human-generated text combined from text in books, articles and websites across a wide range of domains. ChatGPT can assist scientists with material organization, draft creation and proofreading, making it a valuable tool in research and publishing. This paper discusses the use of this artificial intelligence (AI) chatbot in academic writing by presenting one simplified example. Specifically, it reflects our experience of using ChatGPT to draft a scientific article for Reproductive BioMedicine Online and highlights the pros, cons and concerns associated with using LLM-based AI for generating a manuscript.
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Inteligencia Artificial , Médicos , Humanos , Programas Informáticos , Bases de Datos Factuales , EscrituraRESUMEN
Cardiorespiratory fitness (CRF) is inversely associated with cardiovascular disease (CVD) risk factors and brain health impairments. However, the molecular mechanisms linking CRF to health in children are poorly understood. We aimed to examine protein levels related to brain health and CVD in plasma of fit compared to unfit children with overweight/obesity (OW/OB). Eighty-seven children with OW/OB (10.08 ± 1.1 years, 59% boys) from the ActiveBrains project were included. CRF was measured by performing a treadmill test, and children were categorized into fit or unfit. Targeted proteomics in plasma was performed using Olink's proximity extension assay technology of Neurology panel in the whole sample and of Cardiovascular panel in a subsample. Sixteen proteins (PLXNB3, sFRP3, CLEC1B, RSPO1, Gal8, CLEC10A, GCP5, MDGA1, CTSC, LAT, IL4RA, PRSS27, CXCL1, Gal9, MERTK, and GT) were differentially expressed between fit and unfit children with OW/OB after adjusting for sex, maturational status, and body mass index. However, statistically significant differences disappeared after applying FDR correction. Potential candidate proteins related to CRF levels in children with OW/OB were detected, being involved in several biological processes such as neurogenesis, immune/inflammatory response, signal transduction, platelet activation. Nevertheless, these preliminary findings should be confirmed or contrasted in future studies using larger sample sizes, longitudinal and experimental designs.HighlightsThe molecular mechanisms underlying the link of cardiorespiratory fitness (CRF) with cardiovascular and brain health in children with overweight/obesity (OW/OB) are poorly understood.Targeted proteomic analysis revealed differentially expressed proteins (PLXNB3, sFRP3, CLEC1B, RSPO1, Gal8, CLEC10A, GCP5, MDGA1, CTSC, LAT, IL4RA, PRSS27, CXCL1, Gal9, MERTK, and GT) in plasma of "Fit" compared to "Unfit" children with OW/OB. These proteins are involved in several biological processes such as immune/inflammatory response, neurogenesis, signal transduction, and cellular metabolic process.Longitudinal and experimental studies are warranted to reveal how improvements in CRF are related to changes in circulating levels of the abovementioned proteins and how they might reduce cardiovascular diseases risk factors and brain health impairments later in life.
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Capacidad Cardiovascular , Enfermedades Cardiovasculares , Masculino , Humanos , Niño , Femenino , Sobrepeso , Capacidad Cardiovascular/fisiología , Proteómica , Tirosina Quinasa c-Mer , Obesidad , Índice de Masa Corporal , Encéfalo , Factores de Riesgo , Serina EndopeptidasasRESUMEN
BACKGROUND: Emerging research supports the idea that exercise positively affects neurodevelopment. However, the mechanisms linking exercise with brain health are largely unknown. We aimed to investigate the effect of exercise on (a) blood biomarkers selected based on previous evidence (brain-derived neurotrophic factor, ß-hydroxybutyrate (BHB), cathepsin B (CTSB), kynurenine, fibroblast growth factor 21 (FGF21), soluble vascular cell adhesion molecule-1 (sVCAM-1)); and (b) a panel of 92 neurology-related proteins (discovery analysis). We also investigated whether changes in these biomarkers mediate the effects of exercise on brain health (hippocampal structure and function, cognitive performance, and mental health). METHODS: We randomized 81 overweight/obese children (10.1 ± 1.1 years, 41% girls) into 2 groups: either 20 weeks of aerobic plus resistance exercise or control. Candidate biomarkers were assessed using enzyme-linked immunosorbent assay (ELISA) for kynurenine, FGF21, and CTSB; colorimetry for ß-hydroxybutyrate; and XMap for brain-derived neurotrophic factor and soluble vascular cell adhesion molecule-1. The 92 neurology-related proteins were analyzed by an antibody-based proteomic analysis. RESULTS: Our intervention had no significant effect on candidate biomarkers (all p > 0.05). In the discovery analysis, a reduction in circulating macrophage scavenger receptor type-I was observed (standardized differences between groupsâ¯=â¯-0.3, pâ¯=â¯0.001). This effect was validated using ELISA methods (standardized differenceâ¯=â¯-0.3, pâ¯=â¯0.01). None of the biomarkers mediated the effects of exercise on brain health. CONCLUSIONS: Our study does not support a chronic effect of exercise on candidate biomarkers. We observed that while chronic exercise reduced the levels of macrophage scavenger receptor type-I, it did not mediate the effects of exercise on brain health. Future studies should explore the implications of this novel biomarker for overall health.
Asunto(s)
Sobrepeso , Obesidad Infantil , Femenino , Humanos , Niño , Masculino , Sobrepeso/terapia , Factor Neurotrófico Derivado del Encéfalo , Obesidad Infantil/terapia , Molécula 1 de Adhesión Celular Vascular , Ácido 3-Hidroxibutírico , Quinurenina , Proteómica , Encéfalo , Biomarcadores , Terapia por EjercicioRESUMEN
The female lower reproductive tract microbiota is a complex ecosystem comprising various microorganisms that play a pivotal role in maintaining women's reproductive well-being. During pregnancy, the vaginal microbiota undergoes dynamic changes that are important for a successful gestation. This review summarizes the implications of the cervical mucus plug microenvironment and its profound impact on reproductive health. Further, the symbiotic relationship between the vaginal microbiome and the cervical mucus plug is highlighted, with a special emphasis on how this natural barrier serves as a guardian against ascending infections. Understanding this complex host-microbes interplay could pave the way for innovative approaches to improve women's reproductive health and fertility.