Albert Salas Huetos
@urv.cat
Unitat de Medicina Preventiva i Salut Pública, Department of Basic Medical Sciences, Facultat de Medicina i Ciències de la Salut
Universitat Rovira i Virgili
RESEARCH, TEACHING, or OTHER INTERESTS
Reproductive Medicine, Obstetrics and Gynecology, Genetics, Epidemiology
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Iris Martínez-Rodero, Albert Salas-Huetos, Judith Diaz-Muñoz, Erika Alina Ordóñez-León, Tania García-Martínez, Marc Yeste, Carlos Olegario Hidalgo, and Teresa Mogas
Elsevier BV
María Fernández de la Puente, Albert Salas‐Huetos, Cristina Valle‐Hita, Nancy Babio, Michelle M. Murphy, Silvia Canudas, and Jordi Salas‐Salvadó
Wiley
AbstractBackgroundTelomeres are essential for the integrity of chromosome ends during cell division and their involvement in different processes linked to aging has been established. These chromosome components are involved in spermatogenesis and seem to play an important role in fertilization and embryo development. Telomere length is shortened with each cell division. Recently, short sperm telomere length has been proposed as a potential biomarker of male infertility.ObjectivesTo conduct a systematic review and meta‐analysis of studies exploring the association between spermatozoa and/or leukocyte telomere length with sperm quality parameters and different infertility conditions.Material and methodsA systematic review and meta‐analysis was conducted with studies from Medline‐PUBMED and Cochrane Library databases until May 2022. Eligible studies included cohort, cross‐sectional and case–control studies, and telomere length in spermatozoa and/or leukocytes cells was defined as the exposure. Semen quality parameters or infertility conditions (e.g., oligozoospermia, asthenozoospermia, teratozoospermia, or other spermatogenic impairment combinations) were defined as the outcomes.ResultsTwenty‐three observational studies were included. In the qualitative analysis, high heterogeneity was observed between studies regarding the associations between telomere length and semen parameters in different normozoospermic/fertile and oligozoospermic/infertile populations. In the meta‐analysis, spermatozoa and leukocyte telomere length were shorter in infertile individuals than in fertile individuals (mean difference [95% confidence interval]: –1.43 [–1.66 to –1.21], p‐value <0.001 and –1.67 [–2.02 to –1.31], p‐value <0.001, respectively). Moreover, in terms of sperm telomere length, these differences were also significant between individuals with a normal seminogram and individuals with a low quantity of spermatozoa in the ejaculate (–0.97 [–1.32, –0.61], p‐value <0.001).ConclusionThe current systematic review and meta‐analysis suggests the potential role of spermatozoa or leukocyte telomere length as a reliable biomarker of semen quality, which may help distinguish between infertility conditions beyond the routine semen analysis.
Cristina Valle-Hita, Albert Salas-Huetos, María Fernández de la Puente, María Ángeles Martínez, Silvia Canudas, Antoni Palau-Galindo, Cristina Mestres, José María Manzanares, Michelle M Murphy, Montse Marquès,et al.
Oxford University Press (OUP)
Abstract STUDY QUESTION Is ultra-processed food (UPF) consumption associated with semen quality parameters? SUMMARY ANSWER Higher UPF consumption was inversely associated with total sperm count, sperm concentration, and total motility in men of reproductive age. WHAT IS KNOWN ALREADY The consumption of UPF, which has been rising during the last decades, has been demonstrated to be positively associated with several chronic diseases such as diabetes or cardiovascular diseases. However, the scientific evidence on its potential impact on semen quality remains notably limited. STUDY DESIGN, SIZE, DURATION A cross-sectional analysis was conducted using data from 200 healthy men (mean age 28.4 ± 5.5 years) enrolled in the Led-Fertyl (Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters) study between February 2021 and April 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS UPF consumption (% of energy from UPF) was estimated according to the NOVA classification system using a validated 143-item semi-quantitative food frequency questionnaire. Total sperm count, sperm concentration, sperm vitality, total motility, progressive motility, and normal sperm forms were set as the main outcomes. Microscopic parameters were analyzed using a phase-contrast microscope and a computer-assisted sperm analysis (CASA) system. Semen samples were collected and tested according to World Health Organization 2010 standards. Multivariable linear regression models were fitted to estimate the associations between UPF tertile and semen quality parameters. MAIN RESULTS AND THE ROLE OF CHANCE Sperm concentration (β: −1.42 × 106 spz./ml; 95% CI: −2.72 to −0.12) and motility (β: −7.83%; 95% CI: −15.16 to −0.51) were lower in participants in the highest tertile of UPF compared to the lowest. A similar association was observed for sperm count when UPF was analyzed per 10% increment of energy from UPF consumption (β: −1.50 × 106 spz.; 95% CI: −2.83 to −0.17). Theoretically replacing 10% of energy from UPF consumption with 10% of energy from unprocessed or minimally processed food consumption was associated with a higher total sperm count, sperm concentration, total motility, progressive motility, and normal sperm forms. LIMITATIONS, REASONS FOR CAUTION Cross-sectional studies do not permit the drawing of causal inferences. Measurement errors and reporting bias cannot be entirely ruled out. WIDER IMPLICATIONS OF THE FINDINGS This work suggests that consumption of UPF may have an impact on certain semen quality parameters. Furthermore, opting for unprocessed or minimally processed foods instead of UPFs could potentially benefit semen quality. If these results are replicated in future epidemiological studies with different long-term designs, these novel findings could provide valuable insights for updating or even designing preventive and interventional programs to address infertility among men of reproductive age. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Spanish government’s official funding agency for biomedical research, ISCIII, through the Fondo de Investigación para la Salud (FIS), the European Union ERDF/ESF, ‘A way to make Europe’/‘Investing in your future’ [PI21/01447], and the Diputació de Tarragona (2021/11-No.Exp. 8004330008-2021-0022642). J.S.-S. gratefully acknowledges the financial support of ICREA under the ICREA Academia program. C.V.-H. received a predoctoral grant from the Generalitat de Catalunya (2022 FI_B100108). M.Á.M. was supported by the Sara Borrell postdoctoral fellowship (CD21/00045—Instituto de Salud Carlos III (ISCIII)). M.F.d.l.P. was supported by a predoctoral grant from the Rovira i Virgili University and Diputació de Tarragona (2020-PMF-PIPF-8). All authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER N/A.
Elena Sánchez-Resino, Montse Marquès, Daniel Gutiérrez-Martín, Esteban Restrepo-Montes, María Ángeles Martínez, Albert Salas-Huetos, Nancy Babio, Jordi Salas-Salvadó, Rubén Gil-Solsona, and Pablo Gago-Ferrero
American Chemical Society (ACS)
Understanding the potential impact of organic contaminants on male fertility is crucial, yet limited studies have examined these chemicals in semen, with most focusing on urine and blood. To address this gap, we developed and validated a robust LC-HRMS methodology for semen analysis, with a focus on polar and semipolar chemicals. Our methodology enables the quantitative (or semiquantitative) analysis of >2000 chemicals being compatible with suspect and nontarget strategies and providing unprecedented insights into the occurrence and potential bioaccumulation of diverse contaminants in this matrix. We comprehensively analyzed exogenous organic chemicals and associated metabolites in ten semen samples from Spanish participants collected in an area with a large presence of the chemical industry included in the LED-FERTYL Spanish study cohort. This investigation revealed the presence of various contaminants in semen, including plastic additives, PFAS, flame retardants, surfactants, and insecticides. Notably, prevalent plastic additives such as phthalic acid esters and bisphenols were identified, indicating potential health risks. Additionally, we uncovered previously understudied chemicals like the tire additive 2-mercaptobenzothiazole and specific organophosphate flame retardants. This study showcases the potential of our methodology as a valuable tool for large-scale cohort studies, providing insights into the association between contaminant exposure and the risk of male fertility impairments.
Albert Salas-Huetos, Jordi Ribas-Maynou, Yentel Mateo-Otero, Carolina Tamargo, Marc Llavanera, and Marc Yeste
Springer Science and Business Media LLC
Abstract Background MicroRNAs (miRNAs) are small, single-stranded, non-coding RNA molecules of 22–24 nucleotides that regulate gene expression. In the last decade, miRNAs have been described in sperm of several mammals, including cattle. It is known that miRNAs can act as key gene regulators of early embryogenesis in mice and humans; however, little is known about the content, expression, and function of sperm-borne miRNAs in early bovine embryo. In this study, total sperm RNA was isolated from 29 cryopreserved sperm samples (each coming from a separate bull) using a RNeasy kit and treatment with DNase I. RNA concentration and purity were determined through an Epoch spectrophotometer and an Agilent Bioanalyzer. The expression of 10 candidate miRNAs in bovine sperm (bta-miR-10a, bta-miR-10b, bta-miR-138, bta-miR-146b, bta-miR-19b, bta-miR-26a, bta-miR-34a, bta-miR-449a, bta-miR-495 and bta-miR-7), previously identified in testis and/or epididymis, was evaluated with RT-qPCR. The cel-miR-39-3p was used as a spike-in exogenous control. Nonparametric Mann–Whitney tests were run to evaluate which miRNAs were differentially expressed between bulls with high fertility [HF; non-return rates (NRR) ranging from 39.5 to 43.5] and those with subfertility (SF; NRR ranging from 33.3 to 39.3). Several sperm functionality parameters (e.g., viability, membrane stability or oxygen consumption, among others) were measured by multiplexing flow cytometry and oxygen sensing technologies. Results RNA concentration and purity (260/280 nm ratio) (mean ± SD) from the 29 samples were 99.3 ± 84.6 ng/µL and 1.97 ± 0.72, respectively. Bioanalyzer results confirmed the lack of RNA from somatic cells. In terms of the presence or absence of miRNAs, and after applying the Livak method, 8 out of 10 miRNAs (bta-miR-10b, -138, -146b, -19b, -26a, -449a, -495, -7) were consistently detected in bovine sperm, whereas the other two (bta-miR-10a, and -34a) were absent. Interestingly, the relative expression of one miRNA (bta-miR-138) in sperm was significantly lower in the SF than in the HF group (P = 0.038). In addition to being associated to fertility potential, the presence of this miRNA was found to be negatively correlated with sperm oxygen consumption. The expression of three other miRNAs (bta-miR-19b, bta-miR-26a and bta-miR-7) was also correlated with sperm function variables. Conclusions In conclusion, although functional validation studies are required to confirm these results, this study suggests that sperm bta-miR-138 is involved in fertilization events and beyond, and supports its use as a fertility biomarker in cattle.
Albert Salas-Huetos, Makiko Mitsunami, Siwen Wang, Lidia Mínguez-Alarcón, Jordi Ribas-Maynou, Marc Yeste, Irene Souter, Jorge E. Chavarro, Russ Hauser, Paige L Williams,et al.
American Medical Association (AMA)
ImportanceIncreasing evidence suggests that specific foods and nutrients may improve infertility treatment outcomes in women. However, less is known about the role of dietary patterns.ObjectiveTo investigate whether women’s adherence to a priori–defined dietary patterns promoted for the prevention of chronic conditions is associated with outcomes of infertility treatment.Design, Setting, and ParticipantsThis prospective cohort study was conducted at a fertility center at an academic medical center in Boston, Massachusetts. Women undergoing infertility treatment cycles, including intrauterine insemination cycles and in vitro fertilization with or without intracytoplasmic sperm injection were included. Data were collected from January 2007 to October 2019, and data were analyzed from February to December 2022.ExposuresWomen’s pretreatment diet was assessed with a validated food frequency questionnaire from which 8 a priori–defined scores were calculated (higher score indicates greater adherence): (1) Trichopoulou Mediterranean diet, (2) alternate Mediterranean diet, (3) Panagiotakos Mediterranean diet, (4) Healthy Eating Index, (5) Alternate Healthy Eating Index, (6) American Heart Association (AHA) index, (7) Dietary Approaches to Stop Hypertension index, and (8) plant-based diet.Main Outcomes and MeasuresThe adjusted probability of clinically relevant outcomes (live birth as a primary outcome and clinical pregnancy and pregnancy loss as secondary outcomes) was evaluated across quartiles of adherence to each dietary pattern using multivariable generalized linear mixed models to account for repeated cycles.ResultsThis analysis included 612 women with a median (IQR) age of 35.0 (32.0-38.0) years. There was no association between women’s adherence to the 8 a priori dietary patterns and probability of clinical pregnancy or live birth following in vitro fertilization or intrauterine insemination. However, an inverse association was found between adherence to AHA dietary pattern and risks of total and clinical pregnancy loss. Among women who became pregnant during the course of infertility treatment, the adjusted probabilities of pregnancy loss in the lowest and highest quartile of the AHA dietary pattern were 0.41 (95% CI, 0.33-0.50) and 0.28 (95% CI, 0.21–0.36), respectively (P for trend = .02). The corresponding adjusted probabilities of clinical pregnancy loss were 0.30 (95% CI, 0.22-0.39) and 0.15 (95% CI, 0.10-0.23) (P for trend = .007). A similar pattern was observed for all other dietary patterns, with the exception of the plant-based diet pattern.Conclusions and RelevanceFindings of this cohort study suggest that preconception adherence to the AHA diet may be associated with a lower likelihood of pregnancy loss during the course of infertility treatment.
Jordi Ribas-Maynou, Sergi Novo, Albert Salas-Huetos, Sergi Rovira, Marta Antich, and Marc Yeste
Oxford University Press (OUP)
AbstractSTUDY QUESTIONDo defects in sperm chromatin protamination and condensation have an impact on ICSI outcomes?SUMMARY ANSWERSperm protamination is related to fertilization rates in healthy donors, and the in vitro capacity of sperm to condense their chromatin is linked to blastocyst rates, both associations being more apparent in women &lt;33 years of age.WHAT IS KNOWN ALREADYPrevious data on how sperm chromatin damage affects ICSI outcomes are inconsistent. Revealing which sperm factors influence embryo development is necessary to understand the male contribution to ICSI success and to develop novel sperm selection techniques or male-based treatments. Sperm chromatin is mainly condensed in protamines, which are cross-linked through disulphide bridges. This study aimed to determine whether sperm protamination and the integrity of disulphide bonds (condensation) are related to embryo development after ICSI.STUDY DESIGN, SIZE, DURATIONThe design was a retrospective study with a blind analysis of sperm chromatin. Gametes were divided into two groups: double donation (DD) cohort and single donation (SD) cohort. Samples from 45 semen donors used in 55 ICSI cycles with oocyte donors (age range 19–33 years), generating 491 embryos, were included in the DD cohort. The SD cohort consisted of samples from 34 semen donors used in 41 ICSI cycles with oocytes from healthy females (single-parent families or lesbian couples, age range 20–44 years), generating a total of 378 embryos.PARTICIPANTS/MATERIALS, SETTINGS, METHODSDonor sperm samples from DD and SD cohorts were used for standard ICSI, and embryo development was observed by time-lapse imaging. The incidence of thiol reduction (dibromobimane, DBB) and the degree of chromatin protamination (chromomycin A3, CMA3, indicating non-protaminated regions) in sperm were determined by flow cytometry at 0 and 4 h post-thawing.MAIN RESULTS AND THE ROLE OF CHANCEPercentages ± standard deviation of CMA3 were 21.08 ± 9.09 and 35.01 ± 14.68 at 0 and 4 h post-thawing, respectively, in the DD cohort and 22.57 ± 9.48 and 35.79 ± 12.58, at 0 and 4 h post-thawing, respectively, in the SD cohort. Percentages of DBB+ were 16.57 ± 11.10 and 10.51 ± 8.40 at 0 and 4 h post-thawing (P &lt; 0.0001), respectively, in the DD cohort and 17.98 ± 10.19 and 12.72 ± 8.76 at 0 and 4 h post-thawing (P &lt; 0.0001), respectively, in the SD cohort. Female age correlated with fertilization rates, and the relation between sperm chromatin and embryo development was determined through multiple linear regression. While CMA3 was associated with fertilization rates, with no influence of female age, in the DD cohort (β1 = −1.036, P &lt; 0.001 for CMA3; β2 = 0.667, P = 0.304 for female age), this was not observed in the SD cohort, where female age had a significant effect, masking the effects of CMA3 (β1 = −0.066, P = 0.804 for CMA3; β 2 = −1.451, P = 0.003 for female age). The in vitro capacity of sperm to condense their chromatin after 4 h of incubation was associated with blastocyst rates, independent of female age (DD cohort: β1 = −0.238, P = 0.008 for %DBB+ variation; β2 = 0.404, P = 0.638 for female age; SD cohort: β1 = −0.278, P = 0.010 for %DBB+ variation; β2 = −0.292, P = 0.594 for female age). The in vitro capacity of sperm to condense their chromatin was also related to the time required for the embryo to reach blastocyst stage in the DD cohort (P = 0.007). Finally, multiple logistic regression showed that both chromatin protamination and condensation, together with the age of the oocyte donors and the embryo recipients, had an impact on pregnancy achievement (P &lt; 0.01) and on live birth rates (P &lt; 0.01).LIMITATIONS, REASONS FOR CAUTIONThe main limitation was the restrictive selection of couples, which led to a relatively small sample size and could influence the observed outcomes. For this reason, and to reduce Type I error, the level of significance was set at P ≤ 0.01. On the other hand, the use of cryopreserved samples could also be a limitation.WIDER IMPLICATIONS OF THE FINDINGSThis research demonstrated that protamination and condensation of sperm chromatin are related to embryo development after ICSI, but female age could be a confounding factor when oocytes from older females are used.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by the European Union’s Horizon 2020 Research and Innovation scheme under the Marie Skłodowska-Curie grant agreement No 801342 (Tecniospring INDUSTRY; TECSPR-19-1-0003); La Marató de TV3 Foundation (214/857-202039); the Ministry of Science and Innovation, Spain (IJC2019-039615-I); the Catalan Agency for Management of University and Research Grants, Regional Government of Catalonia, Spain (2017-SGR-1229); and the Catalan Institution for Research and Advanced Studies, Spain (ICREA). The authors declare no competing interests.TRIAL REGISTRATION NUMBERN/A.
Carolina Maside, Sandra Recuero, Albert Salas-Huetos, Jordi Ribas-Maynou, and Marc Yeste
Elsevier BV
Linda Tapsell, Joan Sabaté, Raquel Martínez, Marc Llavanera, Elizabeth Neale, and Albert Salas-Huetos
MDPI AG
Nuts have formed part of human diets throughout the ages. In recent decades, research has shown they are key foods in dietary patterns associated with lower chronic disease risk. The current state of climate change, however, has introduced an imperative to review the impact of dietary patterns on the environment with a shift to plant-based diets. Nuts emerge as a significant source of protein in plant-based diets and are a minimally processed and sustainable food. Research in this area is evolving to drive better production methods in varying climate conditions. Nevertheless, nut consumption remains an important contributor to human health. The mechanisms of action can be explained in terms of the nutrients they deliver. Studies of nut consumption have linked components such as monounsaturated fatty acids, plant omega-3 fatty acids, antioxidants, and plant sterols to improved lipoprotein profiles, lower blood pressure, and reduced cardiovascular disease risk. Preliminary research also indicates possible beneficial effects of nut consumption on reproductive health. In any case, the ultimate effects of foods on health are the results of multiple interactive factors, so where nuts fit within dietary patterns is a significant consideration for research translation. This has implications for research methodologies, including categorization within food groups and inclusion in Healthy Dietary Indices. The aim of this narrative review is to outline new focal points for investigation that examine the environmental and some novel human health impacts of nut consumption and discuss future directions for research.
Jordi Ribas-Maynou, Isabel Barranco, and Albert Salas-Huetos
MDPI AG
Recent research has focused on the understanding of the causes of subfertility observed in livestock species, evidencing that different factors could underlie this condition [...]
María Ángeles Martínez, Montse Marquès, Albert Salas-Huetos, Nancy Babio, José L. Domingo, and Jordi Salas-Salvadó
Elsevier BV
Albert Salas-Huetos, Sergi Bonet, and Jordi Ribas-Maynou
Frontiers Media SA
One of the most astonishing processes in nature is the creation of a new individual from two single superspecialized cells; the oocyte and the sperm. Gamete quality and fertilization process is of great interest to the general population and has wide implications for human health. Although outstanding research has been in this area, many questions remain unanswered. For example, why reproductive health seems to be declining over the last few years? (GBD 2017 Population and Fertility Collaborators et al., 2018; Levine et al., 2017; Skakkebaek et al., 2019; Levine et al., 2022). This problem has resulted into an increase of around 20% in the total number of assisted reproductive technology (ART) cycles in the last two decades (de Mouzon et al., 2020). The current Research Topic on “Gamete quality and assisted reproductive technology (ART) outcomes” has collected cutting-edge original research on these key topics from an interdisciplinary perspective, representing the current research progress in this dynamic and central discipline. The Research Topic currently includes four papers. Firstly, in “MicroRNA-targeting in male infertility: Sperm microRNA-19a/ b-3p and its spermatogenesis related transcripts content in men with oligoasthenozoospermia,” Abu-Halima and collaborators add some spark to the role of sperm microRNAs (miRNAs) in infertility (Abu-Halima et al.). Several papers reported on the essential role of sperm miRNAs for spermatogenesis and early embryo development (Salas-Huetos et al., 2019; Salas-Huetos et al., 2020), however, the miRNA-mRNA interaction is not well understood yet for the vast majority of miRNAs. In the paper published on this Research Topic, the expression levels of both hsa-miR-19a-3p and -19b-3p were measured in 82 age-matched men (41 normozoospermic and 41 oligoasthenozoospermic). An upregulation of miR-19a/ b-3p in oligoasthenozoospermic men was found. In an in silico prediction of miR19a/b-3p target genes, 130 mRNA were identified and 82 were selected for RT-qPCR validation based on their role in sperm function or spermatogenesis. The authors described 51 target genes significantly downregulated in oligoasthenozoospermic men and, interestingly, suggest that the higher expression of both miRNAs (hsa-miROPEN ACCESS
Marc Llavanera, Ariadna Delgado-Bermudez, Jordi Ribas-Maynou, Albert Salas-Huetos, and Marc Yeste
Elsevier BV
Jordi Ribas-Maynou, Sergi Novo, Marc Torres, Albert Salas-Huetos, Sergi Rovira, Marta Antich, and Marc Yeste
Springer Science and Business Media LLC
AbstractBased on the inconsistent literature published thus far involving infertile patients, whether intracytoplasmic sperm injection (ICSI) allows overcoming total fertilization failure due to sperm DNA fragmentation is still unclear. Related to this, female factors, which may have a significant impact on assisted reproduction outcomes, can mask male infertility. In this scenario, evaluating ICSI outcomes following cycles using healthy donor gametes could shed light on this realm, as it would avoid the influence of (un)known confounding factors present in infertile individuals. The present work, therefore, aimed to address whether single- and double-stranded sperm DNA fragmentation leads to impaired ICSI outcomes in double gamete donation cycles. The study also compared these double-gamete donation cycles to cycles in which only sperm were donated and oocytes were obtained from infertile patients. Two cohorts were included: (a) the Donor-Donor (DD) cohort, which included 27 semen donor samples used in 49 ICSI cycles with young healthy oocyte donors; and (b) the Donor-Infertile (DI) cohort, which involved 34 semen donor samples used in 57 ICSI cycles with oocytes from patients. Single- and double-stranded sperm DNA breaks were determined with alkaline and neutral Comet assays, respectively; ICSI was conducted following standard protocols and embryos were monitored through time-lapse microscopy. In the DD cohort, the percentage of sperm with high overall DNA damage correlated with fertilization rates (Rs = − 0.666;P < 0.001) and with the percentage of blastocysts per injected oocyte (Rs = − 0.414;P = 0.040). In addition, sperm DNA damage delayed the first embryo division (Rs = 0.421;P = 0.036), and development from the 8-cell to the morula stage (Rs = 0.424;P = 0.034). In contrast, double-stranded DNA breaks had no effect in this cohort. As far as the DI cohort is concerned, while overall sperm DNA damage was not found to be correlated to fertilization or blastocyst rates, pronuclei formation following ICSI was delayed when the incidence of double-stranded DNA breaks was high (Rs = 0.485;P = 0.005). In conclusion, this study, which is the first involving double donation cycles (i.e., a donor-donor cohort), supports that sperm DNA damage has a detrimental impact on fertilization rates after ICSI, and delays embryo development. Moreover, the use of oocytes from infertile individuals is suggested to hide the male-factor effect.
Iris Martínez‐Rodero, Albert Salas‐Huetos, Alina Ordóñez‐León, Carlos Olegario Hidalgo, Marc Yeste, Elena Mercadé, and Teresa Mogas
Wiley
AbstractThe cold‐adapted bacterium Pseudomonas sp. ID1 produces the extracellular exopolysaccharide ID1 (EPS ID1) with cryoprotective activity. This study was designed to optimize the vitrification/in‐straw warming protocol of in vitro‐produced (IVP) blastocysts by adding EPS ID1 to the vitrification media. Day 7‐expanded blastocysts were vitrified/warmed using the VitTrans device after the addition of 0 or 100 μg/mL EPS ID1 to the vitrification media. Blastocysts vitrified by the Cryotop method and fresh non‐vitrified blastocysts served as controls. Outcomes were assessed in the warmed embryos in terms of survival rates and mRNA relative abundances of BAX, BCL2, GPX1, and CDX2 genes. No differences in survival rates were observed at 3 h post‐warming between vitrification treatments. At 24 h post‐warming, the addition of EPS prior to vitrification with the VitTrans device produced similar survival rates to Cryotop‐vitrified embryos and similar hatching rates to fresh non‐vitrified or Cryotop‐vitrified embryos. No differences emerged in BCL2 gene expression. Lower BAX (p < .05) and higher GPX1 (p < .05) and CDX2 (p < .1) gene expression were observed in expanded and/or hatched blastocysts derived from VitTrans‐EPS‐vitrified embryos when compared to those from the non‐supplemented group. In conclusion, addition of EPS not only promoted blastocyst survival and hatching after VitTrans vitrification/warming but also modified the expression of genes associated with better embryo quality.
Marc Llavanera, Ariadna Delgado-Bermúdez, Jordi Ribas-Maynou, Albert Salas-Huetos, and Marc Yeste
Elsevier BV
Albert Salas-Huetos, Mariel Arvizu, Lidia Mínguez-Alarcón, Makiko Mitsunami, Jordi Ribas-Maynou, Marc Yeste, Jennifer B. Ford, Irene Souter, and Jorge E. Chavarro
Elsevier BV
Cristina Bouzas, Maria del Mar Bibiloni, Silvia Garcia, David Mateos, Miguel Ángel Martínez-González, Jordi Salas-Salvadó, Dolores Corella, Albert Goday, J. Alfredo Martínez, Ángel M. Alonso-Gómez,et al.
Frontiers Media SA
BackgroundMetabolic syndrome (MetS) worsens quality of life and increases mortality. Dissatisfaction with weight in patients with MetS may modify the effect of lifestyle interventions to achieve changes in health-related behaviors.ObjectiveTo assess 1-year changes in cardiovascular risk scores, self-perceived general health and health-related behaviors according to observed changes in desired weight loss during the first year of intervention in a large cardiovascular prevention trial.DesignProspective analysis of the PREDIMED-PLUS trial, including 5,499 adults (55–75 years old) with overweight or obesity at baseline.MethodsThe desired weight loss was the difference between ideal and measured weight. Tertiles of change in desired weight loss (1 year vs. baseline) were defined by the following cut-off points: ≥0.0 kg (T1, n = 1,638); 0.0 to −4.0 kg (T2, n = 1,903); ≤−4.0 kg (T3, n = 1,958). A food frequency questionnaire assessed diet and the Minnesota-REGICOR questionnaire assessed physical activity. The Framingham equation assessed cardiovascular risks. The changes in the severity of MetS were also assessed. The Beck Depression Inventory assessed depressive symptoms and the SF-36 assessed health-related quality of life. Data were analyzed using general linear models.ResultsBMI decreased at T2 and T3 (T1: 0.3, T2: −0.7, T3: −1.9). The most significant improvement in diet quality was observed at T3. Cardiovascular risk decreased at T2 and T3. Mean reductions in MetS severity score were: −0.02 at T1, −0.39 at T2 and −0.78 at T3. The perception of physical health increases in successive tertiles.ConclusionsIn older adults with MetS, more ambitious desired weight loss goals were associated with improvements in diet, cardiovascular health and perceived physical health during the first year of a healthy lifestyle intervention programme. Weight dissatisfaction needs to be considered by health professionals.Clinical trial registrationhttp://www.isrctn.com/ISRCTN89898870, identifier 89898870.
Isabel Barranco, Albert Salas-Huetos, Angel Berlanga, Marcella Spinaci, Marc Yeste, and Jordi Ribas-Maynou
CSIRO Publishing
In recent years, extracellular vesicles (EVs) have emerged as essential players in cell-to-cell communication, particularly having an active regulating role in biological systems. Because reproductive-associated processes are not exempt of this communication, multiple studies have been devoted to this realm, focusing on gamete maturation, embryo implantation or fetal development. The aim of the present review was to comprehensively and systematically collect evidence about the function of the microRNA (miRNA) encapsulated in EVs isolated from different reproductive tissues or fluids in reproductive-related diseases. Following PRISMA guidelines, we conducted a systematic search of the literature published in MEDLINE-PubMed until the end of February 2021. After selection, 32 studies were included in the qualitative review comparing the miRNA expression profile in EVs between different pathological disorders. Most reports showed the potential of the miRNAs carried by EVs to be used as putative biomarkers of reproductive disorders, including pregnancy affections, disease progression and quality of preimplantation embryos. The most relevant miRNAs were found to be highly heterogeneous among studies, with some conflicting results. Further research is thus warranted to address whether cofounding factors, such as the methods to isolate EVs and miRNAs, the subset of EVs, the criteria of patient selection, the timing of sample retrieval, or any other factor, may explain the inconsistencies between studies.
Haiyang Bian, Lidia Mínguez-Alarcón, Albert Salas-Huetos, David Bauer, Paige L Williams, Irene Souter, Jill Attaman, and Jorge E Chavarro
Elsevier BV
BACKGROUND
Male obesity has been related to poor semen quality and may also have a negative effect on assisted reproductive technologies (ART) outcomes. Whether male waist circumference (WC), as a measure of central obesity, impacts a couple's fertility independently of body mass index is unclear.
OBJECTIVE
To examine the associations of male WC with semen quality and couples' outcomes of infertility treatment with ART.
DESIGN
Couples presenting to the Massachusetts General Hospital Fertility Center were invited to participate in the study. Between 2009 and 2019, 269 males provided 671 semen samples and 176 couples underwent 317 ART cycles. Height, weight and WC were measured on-site. We analyzed the association of male WC with semen quality and pregnancy outcomes using cluster-weighted regression models to account for repeated observations while adjusting for potential confounders. Models were also stratified by male BMI (<25 vs. ≥25 kg/m2).
RESULTS
Median male age, WC and BMI were 36.1 years, 96.0 cm and 26.8 kg/m2, respectively. A 5 cm increase in WC was associated with a 6.3% (95% confidence interval: 2.1, 10.5%) lower sperm concentration after adjustment for potential confounders including BMI. Male WC was also inversely related to the probability of achieving a live birth. For each 5 cm increase in male WC, the odds (95% confidence interval) of live birth per initiated cycle decreased by 9.0% (1.1, 16.4%) after accounting for several anthropometric and demographic characteristics of both partners. These associations were stronger among males in the normal BMI category (<25 kg/m2) than among overweight or obese males.
CONCLUSIONS
Higher male WC may be an additional risk factor for poor outcomes of infertility treatment, even after accounting for male and female partner BMI, and particularly in couples where the male partner has a normal BMI.
Albert Salas-Huetos, Lidia Mínguez-Alarcón, Makiko Mitsunami, Mariel Arvizu, Jennifer B. Ford, Irene Souter, Marc Yeste, and Jorge E. Chavarro
Elsevier BV
Brendan J Houston, Antoni Riera-Escamilla, Margot J Wyrwoll, Albert Salas-Huetos, Miguel J Xavier, Liina Nagirnaja, Corinna Friedrich, Don F Conrad, Kenneth I Aston, Csilla Krausz,et al.
Oxford University Press (OUP)
Abstract BACKGROUND Human male infertility has a notable genetic component, including well-established diagnoses such as Klinefelter syndrome, Y-chromosome microdeletions and monogenic causes. Approximately 4% of all infertile men are now diagnosed with a genetic cause, but a majority (60–70%) remain without a clear diagnosis and are classified as unexplained. This is likely in large part due to a delay in the field adopting next-generation sequencing (NGS) technologies, and the absence of clear statements from field leaders as to what constitutes a validated cause of human male infertility (the current paper aims to address this). Fortunately, there has been a significant increase in the number of male infertility NGS studies. These have revealed a considerable number of novel gene–disease relationships (GDRs), which each require stringent assessment to validate the strength of genotype–phenotype associations. To definitively assess which of these GDRs are clinically relevant, the International Male Infertility Genomics Consortium (IMIGC) has identified the need for a systematic review and a comprehensive overview of known male infertility genes and an assessment of the evidence for reported GDRs. OBJECTIVE AND RATIONALE In 2019, the first standardised clinical validity assessment of monogenic causes of male infertility was published. Here, we provide a comprehensive update of the subsequent 1.5 years, employing the joint expertise of the IMIGC to systematically evaluate all available evidence (as of 1 July 2020) for monogenic causes of isolated or syndromic male infertility, endocrine disorders or reproductive system abnormalities affecting the male sex organs. In addition, we systematically assessed the evidence for all previously reported possible monogenic causes of male infertility, using a framework designed for a more appropriate clinical interpretation of disease genes. SEARCH METHODS We performed a literature search according to the PRISMA guidelines up until 1 July 2020 for publications in English, using search terms related to ‘male infertility’ in combination with the word ‘genetics’ in PubMed. Next, the quality and the extent of all evidence supporting selected genes were assessed using an established and standardised scoring method. We assessed the experimental quality, patient phenotype assessment and functional evidence based on gene expression, mutant in-vitro cell and in-vivo animal model phenotypes. A final score was used to determine the clinical validity of each GDR, across the following five categories: no evidence, limited, moderate, strong or definitive. Variants were also reclassified according to the American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) guidelines and were recorded in spreadsheets for each GDR, which are available at imigc.org. OUTCOMES The primary outcome of this review was an overview of all known GDRs for monogenic causes of human male infertility and their clinical validity. We identified a total of 120 genes that were moderately, strongly or definitively linked to 104 infertility phenotypes. WIDER IMPLICATIONS Our systematic review curates all currently available evidence to reveal the strength of GDRs in male infertility. The existing guidelines for genetic testing in male infertility cases are based on studies published 25 years ago, and an update is far overdue. The identification of 104 high-probability ‘human male infertility genes’ is a 33% increase from the number identified in 2019. The insights generated in the current review will provide the impetus for an update of existing guidelines, will inform novel evidence-based genetic testing strategies used in clinics, and will identify gaps in our knowledge of male infertility genetics. We discuss the relevant international guidelines regarding research related to gene discovery and provide specific recommendations to the field of male infertility. Based on our findings, the IMIGC consortium recommend several updates to the genetic testing standards currently employed in the field of human male infertility, most important being the adoption of exome sequencing, or at least sequencing of the genes validated in this study, and expanding the patient groups for which genetic testing is recommended.
F L Nassan, L Priskorn, A Salas-Huetos, T I Halldorsson, T K Jensen, N Jørgensen, and J E Chavarro
Oxford University Press (OUP)
Abstract STUDY QUESTION Is intake of sugar-sweetened beverages (SSB) or artificially sweetened beverages (ASB) associated with testicular function in young men? SUMMARY ANSWER Among young men unaware of their semen quality and reproductive hormone levels, intake of SSBs was associated with lower sperm concentration, lower total sperm count, and a lower ratio of serum inhibin-B/FSH. WHAT IS KNOWN ALREADY SSBs may adversely impact testicular function, but results are not consistent across studies. Moreover, the associations of ASB, energy-drinks or fruit juices with testicular function are unclear. STUDY DESIGN, SIZE, DURATION Young healthy men and unselected for fertility status men enrolled in a cross-sectional study between 2008 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 2935 young (median age: 19 years) men enrolled in the study. Intake of SSBs, ASBs, fruit juices, and energy-drinks was assessed with a validated food frequency questionnaire. Testicular function was assessed through conventional semen quality parameters (semen volume, sperm concentration, total count, motility and morphology), testicular volume assessed with ultrasound, and serum reproductive hormone concentrations (total testosterone, free testosterone, E2, inhibin-B, LH, FSH, sex hormone-binding globulin) were measured. MAIN RESULTS AND THE ROLE OF CHANCE In multivariable-adjusted analyses, men in the highest category of SSB intake (median: 1.1 servings (∼220 ml)/day) had a 13.2 million/ml lower median sperm concentration (95% CI: –21.0, –5.5) than non-consumers. A similar pattern was observed with total sperm count (–28 million (95% CI: –48, –9)), serum inhibin-B (–12 pg/ml (95% CI: –21, –4)), and inhibin-B/FSH ratio (–9 (95% CI: –18, 0)). The adjusted median difference in sperm concentration and inhibin-B associated with increasing SSB intake by 1 serving (∼200ml)/day at the expense of water was –3.4 million sperm/ml (95% CI: –5.8, –1.0) and –7 pg/ml (95% CI: –11, –3), respectively. LIMITATIONS, REASONS FOR CAUTION Inferring causality is limited owing to the cross-sectional design. We adjusted for a number of potential confounders but cannot exclude that unmeasured lifestyle and behavior associated with soft drink intake is associated with testicular function in these young men. WIDER IMPLICATIONS OF THE FINDINGS In the largest study to date, intake of SSBs was associated with lower sperm concentration, total sperm count, and serum inhibin-B/FSH ratio, consistent with a direct suppressive effect of SSB intake on testicular function among otherwise healthy men, potentially affecting fertility. However, the observed association between higher SSB intake and lower semen quality does not necessarily imply a decrease in fertility. STUDY FUNDING/COMPETING INTEREST(S) Supported by research from the Danish Council for Strategic Research (2101-08-0058), Independent Research Fund Denmark (8020-00218B), European Union (212844), the Kirsten and Freddy Johansen’s Foundation (95-103-72087), the Research Fund of the Capital Region of Denmark (A6176), and the NIH (P30DK046200). The authors report no conflict of interest. TRIAL REGISTRATION NUMBER N/A.
Marc Yeste, Sandra Recuero, Carolina Maside, Albert Salas-Huetos, Sergi Bonet, and Elisabeth Pinart
MDPI AG
Few data exist about the presence and physiological role of Na+/H+ exchangers (NHEs) in the plasma membrane of mammalian sperm. In addition, the involvement of these channels in the ability of sperm to undergo capacitation and acrosomal reaction has not been investigated in any mammalian species. In the present study, we addressed whether these channels are implicated in these two sperm events using the pig as a model. We also confirmed the presence of NHE1 channels in the plasma membrane of ejaculated sperm by immunofluorescence and immunoblotting. The function of NHE channels during in vitro capacitation was analyzed by incubating sperm samples in capacitating medium for 300 min in the absence or presence of a specific blocker (DMA; 5-(N,N-dimethyl)-amiloride) at different concentrations (1, 5, and 10 µM); acrosome exocytosis was triggered by adding progesterone after 240 min of incubation. Sperm motility and kinematics, integrity of plasma and acrosome membranes, membrane lipid disorder, intracellular calcium and reactive oxygen species (ROS) levels, and mitochondrial membrane potential (MMP) were evaluated after 0, 60, 120, 180, 240, 250, 270, and 300 min of incubation. NHE1 localized in the connecting and terminal pieces of the flagellum and in the equatorial region of the sperm head and was found to have a molecular weight of 75 kDa. During the first 240 min of incubation, i.e., before the addition of progesterone, blocked and control samples did not differ significantly in any of the parameters analyzed. However, from 250 min of incubation, samples treated with DMA showed significant alterations in total motility and the amplitude of lateral head displacement (ALH), acrosomal integrity, membrane lipid disorder, and MMP. In conclusion, while NHE channels are not involved in the sperm ability to undergo capacitation, they could be essential for triggering acrosome exocytosis and hypermotility after progesterone stimulus.
Makiko Mitsunami, Albert Salas-Huetos, Lidia Mínguez-Alarcón, Jill A. Attaman, Jennifer B. Ford, Martin Kathrins, Irene Souter, and Jorge E. Chavarro
Elsevier BV