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2.
Cells ; 8(12)2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31817143

RESUMO

The recent discovery of microRNAs (miRNAs) in human reproductive tissues and cells indicates a possible functional role in reproductive function. However, the studies published to date in female reproductive tissues/cells and embryos are inconclusive and sometimes controversial. In order to update the knowledge of this field, the present study aimed to discuss, through a systematic review, the role of miRNAs in female human reproduction and early embryogenesis. We conducted a systematic review of the published literature in MEDLINE and EMBASE databases through June 2018 (plus a complementary search until July 2019), in accordance with the PRISMA guidelines. We have included descriptive and observational studies, in which fertile/infertile women were well-defined. The primary outcome was the miRNA expression in ovaries, oocytes, extracellular vesicles, and embryos. We identified 25,204 articles, of which 28 were selected for qualitative analysis: 18 in ovaries and extracellular vesicles, three in oocytes, and seven in embryos. The present systematic review of descriptive and observational studies demonstrates that aberrant miRNA expression in female reproductive tissues/cells and embryos is related with infertility and embryogenesis errors. The expression of specific miRNAs, particularly in extracellular vesicles, may be used in the future as biomarkers of infertility and prognostic tools of embryo development.

3.
Epigenetics Chromatin ; 12(1): 74, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31856899

RESUMO

BACKGROUND: The impact of aging on the sperm methylome is well understood. However, the direct, subsequent impact on offspring and the role of altered sperm DNA methylation alterations in this process remain poorly understood. The well-defined impact of aging on sperm DNA methylation represents an excellent opportunity to trace the direct, transgenerational transmission of these signals. RESULTS: We utilized the Illumina MethylationEPIC array to analyze the sperm of 16 patients with older (> 40 years of age) paternal grandfathers ('old grand paternal age' patients; OGPA) and 16 patients with younger (< 25 years of age) grandfathers ('young grand paternal age' patients; YGPA) identified through the Subfertility Health Assisted Reproduction and the Environment (SHARE) cohort to investigate differences in DNA methylation. No differentially methylated regions were identified between the OGPA and YGPA groups. Further, when assessing only the sites previously shown to be altered by age, no statistically significant differences between OGPA and YGPA were identified. This was true even despite the lower bar for significance after removing multiple comparison correction in a targeted approach. Interestingly though, in an analysis of the 140 loci known to have decreased methylation with age, the majority (~ 72%) had lower methylation in OGPA compared to YGPA though the differences were extremely small (~ 1.5%). CONCLUSIONS: This study suggests that the robust and consistent age-associated methylation alterations seen in human sperm are 'reset' during large-scale epigenetic reprograming processes and are not directly inherited trans-generationally (over two generations). An extremely small trend was present between the YGPA and OGPA groups that resemble the aging pattern in older sperm. However, this trend was not significant and was so small that, if real, is almost certainly biologically inert.

4.
Cardiovasc Diabetol ; 18(1): 151, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722714

RESUMO

BACKGROUND: The pandemic of cardiovascular disease (CVD) and type 2 diabetes (T2D) requires the identification of new predictor biomarkers. Biomarkers potentially modifiable with lifestyle changes deserve a special interest. Our aims were to analyze: (a) The associations of lysine, 2-aminoadipic acid (2-AAA) or pipecolic acid with the risk of T2D or CVD in the PREDIMED trial; (b) the effect of the dietary intervention on 1-year changes in these metabolites, and (c) whether the Mediterranean diet (MedDiet) interventions can modify the effects of these metabolites on CVD or T2D risk. METHODS: Two unstratified case-cohort studies nested within the PREDIMED trial were used. For CVD analyses, we selected 696 non-cases and 221 incident CVD cases; for T2D, we included 610 non-cases and 243 type 2 diabetes incident cases. Metabolites were quantified using liquid chromatography-tandem mass spectrometry, at baseline and after 1-year of intervention. RESULTS: In weighted Cox regression models, we found that baseline lysine (HR+1 SD increase = 1.26; 95% CI 1.06-1.51) and 2-AAA (HR+1 SD increase = 1.28; 95% CI 1.05-1.55) were both associated with a higher risk of T2D, but not with CVD. A significant interaction (p = 0.032) between baseline lysine and T2D on the risk of CVD was observed: subjects with prevalent T2D and high levels of lysine exhibited the highest risk of CVD. The intervention with MedDiet did not have a significant effect on 1-year changes of the metabolites. CONCLUSIONS: Our results provide an independent prospective replication of the association of 2-AAA with future risk of T2D. We show an association of lysine with subsequent CVD risk, which is apparently diabetes-dependent. No evidence of effects of MedDiet intervention on lysine, 2-AAA or pipecolic acid changes was found. Trial registration ISRCTN35739639; registration date: 05/10/2005; recruitment start date 01/10/2003.

5.
Fertil Steril ; 112(5): 831-841, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31587805

RESUMO

OBJECTIVE: To identify candidates of fertility biomarkers among pairs of human sperm microRNAs. DESIGN: Expression data of 736 sperm microRNAs from fertile and infertile individuals characterized in previous published studies by means of TaqMan quantitative polymerase chain reaction (PCR) were reexamined. A set of microRNA pairs with the best biomarker potential were selected and validated by means of quantitative real-time (qRT) PCR in an independent cohort. SETTING: University laboratory. PATIENT(S): Semen samples were obtained from fertile (n = 10) and infertile (asthenozoospermia, n = 10; teratozoospermia, n = 10; oligozoospermia, n = 10; unexplained male infertility [UMI], n = 8) individuals. The validation cohort included 9 fertile donors and 14 infertile patients with different seminal alterations. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Spearman test was used to select microRNA pairs with a correlated expression in fertile individuals and a noncorrelated expression in each infertile group. The biomarker potential of these pairs was determined with the use of receiver operating characteristic curves. The differential relative expression of each pair in fertile and infertile populations was verified (Mann-Whitney test). Those pairs with best results were validated by qRT-PCR. RESULT(S): Forty-eight pairs showed significant correlations in the fertile group. The pairs that were uncorrelated in the infertile populations and displayed the best biomarker potential were hsa-miR-942-5p/hsa-miR-1208 (asthenozoospermia), hsa-miR-296-5p/hsa-miR-328-3p (teratozoospermia), hsa-miR-139-5p/hsa-miR-1260a (oligozoospermia), and hsa-miR-34b-3p/hsa-miR-93-3p (UMI). The hsa-miR-942-5p/hsa-miR-1208 pair showed the greatest potential for detecting seminal alterations in the validation cohort (85.71% true positives). CONCLUSION(S): The pairs hsa-miR-942-5p/hsa-miR-1208 and hsa-miR-34b-3p/hsa-miR-93-3p have the potential to become new molecular biomarkers that could help to diagnose male infertility, especially in cases of UMI or when seminal parameters are close to the threshold values.

6.
Reprod Biol ; 19(3): 219-224, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31375368

RESUMO

Human semen quality has declined worldwide in the last 40 years, by some accounts as much as 50-60%, causing serious concerns and implications for human fertility. Even though it has been shown to be a worldwide problem, this decrease is more pronounced in developed and industrialized countries, pointing to changes in modifiable lifestyle factors (e.g. unhealthy diets, lifestyles, and pollution) as the main causes. Studies investigating the relation between diet and semen quality can be classified into three groups; studies assessing the association between semen quality and 1) nutrients, dietary supplements and antioxidants, 2) food, and 3) dietary patterns. The present narrative review provides a wide-ranging vision of the positive associations and effects of diet on sperm quality. Although the picture of the relationship between diet and sperm quality and fertility is far from complete, a number of broad conclusions have emerged. First, increased intake of selenium and zinc, omega-3 (ω-3) fatty acids, CoenzymeQ10 (CoQ10) and carnitine supplements have been positively related to sperm quality. In terms of food groups, vegetables, fruits, nuts and whole cereals, all rich in fiber and antioxidants, and fish, seafood, shellfish, poultry, and low-fat dairy products have been positively associated with sperm quality. Finally, adherence to healthy dietary patterns is positively associated with sperm concentration and sperm motility.

7.
Nutr. hosp ; 36(4): 981-987, jul.-ago. 2019. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-184726

RESUMO

Alexandre Frias nació en Reus, ciudad donde desarrolló la mayor parte de su actividad profesional. Médico y puericultor, trabajó incansablemente con el fin de mejorar la salud infantil. Creó el primer Instituto de Puericultura integral de España en 1919, que se mantuvo en funcionamiento hasta su muerte. Las actividades del instituto se iniciaron con un consultorio para niños lactantes, servicio de lactario y un laboratorio de análisis, y se ampliaron posteriormente con servicios de puericultura prenatal, refectorio para embarazadas y mujeres, un consultorio de pediatría con servicio de vacunación y, como complemento, un servicio de asistencia domiciliaria de comadrona y un médico tocólogo. Convencido de que la lactancia materna y la higiene eran fundamentales para la prevención de enfermedades, realizó una ingente labor educativa entre madres, médicos, gobernantes y sociedad en general. Precursor de numerosas iniciativas con fines curativos y preventivos, instauró la educación sanitaria para madres y profesionales, las colonias escolares, la inspección médica-escolar, el servicio a domicilio de básculas para control de peso e incubadoras para niños prematuros e incluso un modelo de vestido higiénico para recién nacidos. Realizó numerosas publicaciones en forma de libros, como el titulado "Lo que deben saber las madres", opúsculos y artículos de prensa. Fundó y dirigió la revista Puericultura, editada en Reus y distribuida a todo el país, que se publicó hasta 1936. Su incesante actividad en pro de la lucha contra la mortalidad infantil redujo drásticamente las muertes en Reus e influyó en la mejora sanitaria y demográfica de toda España


Alexandre Frias was born in Reus, the city where he developed most of his professional activity. Medical doctor and childcare pediatrician, he worked tirelessly in order to improve children's health. He created the first Instituto de Puericultura Integral (Integral Institute of Childcare) in Spain in 1919, which remained in operation until his death. The Institute's activities began with a clinic for breastfeeding children, breastfeeding service and a biochemical analysis laboratory, later expanding with prenatal childcare services, a refectory for pregnant women and general women, a pediatric office with a vaccination service and, as a complement, a home health care service and medical obstetrics. Convinced that breastfeeding and hygiene were fundamental for the prevention of diseases, he carried out an enormous educational work among mothers, doctors, governors and society in general. Forerunner of numerous initiatives for curative and preventive purposes, he established health education for mothers and professionals, school colonies, medical-school inspection, home delivery of scales for weight control and incubators for premature children and even a hygienic dress model for newborns. He made numerous publications as books form, such as the one entitled "Lo que deben saber las madres", booklets and newspapers articles. He founded and directed the scientific journal Puericultura (child care), published in Reus and distributed throughout the country until 1936. Its incessant activity in favor of the fight against infant mortality drastically reduced infant/children mortality in Reus and influenced the health and demographic improvement of all of Spain


Assuntos
Humanos , História do Século XX , Cuidado da Criança/história , Aleitamento Materno/história , Mortalidade Infantil/história , Transtornos da Nutrição Infantil/história , Transtornos da Nutrição Infantil/prevenção & controle , Desnutrição/epidemiologia , Desnutrição/história , Desnutrição/prevenção & controle
8.
Nutr Hosp ; 36(4): 981-987, 2019 Aug 26.
Artigo em Espanhol | MEDLINE | ID: mdl-31244321

RESUMO

Introduction: Alexandre Frias was born in Reus, the city where he developed most of his professional activity. Medical doctor and childcare pediatrician, he worked tirelessly in order to improve children's health. He created the first Instituto de Puericultura Integral (Integral Institute of Childcare) in Spain in 1919, which remained in operation until his death. The Institute's activities began with a clinic for breastfeeding children, breastfeeding service and a biochemical analysis laboratory, later expanding with prenatal childcare services, a refectory for pregnant women and general women, a pediatric office with a vaccination service and, as a complement, a home health care service and medical obstetrics. Convinced that breastfeeding and hygiene were fundamental for the prevention of diseases, he carried out an enormous educational work among mothers, doctors, governors and society in general. Forerunner of numerous initiatives for curative and preventive purposes, he established health education for mothers and professionals, school colonies, medical-school inspection, home delivery of scales for weight control and incubators for premature children and even a hygienic dress model for newborns. He made numerous publications as books form, such as the one entitled "Lo que deben saber las madres", booklets and newspapers articles. He founded and directed the scientific journal Puericultura (child care), published in Reus and distributed throughout the country until 1936. Its incessant activity in favor of the fight against infant mortality drastically reduced infant/children mortality in Reus and influenced the health and demographic improvement of all of Spain.

9.
Nutrients ; 11(6)2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31248067

RESUMO

Lifestyle risk factors for erectile and sexual function include smoking, excessive alcohol consumption, lack of physical activity, psychological stress, and adherence to unhealthy diets. In the present study, we evaluated the effects of mixed nuts supplementation on erectile and sexual function. Eighty-three healthy male aged 18-35 with erectile function assessment were included in this FERTINUTS study sub-analysis; a 14-week randomized, controlled, parallel feeding trial. Participants were allocated to (1) the usual Western-style diet enriched with 60 g/day of a mixture of nuts (nut group; n = 43), or (2) the usual Western-style diet avoiding nuts (control group; n = 40). At baseline and the end of the intervention, participants answered 15 questions contained in the validated International Index of Erectile Function (IIEF), and peripheral levels of nitric oxide (NO) and E-selectin were measured, as surrogated markers of erectile endothelial function. Anthropometrical characteristics, and seminogram and blood biochemical parameters did not differ between intervention groups at baseline. Compared to the control group, a significant increase in the orgasmic function (p-value = 0.037) and sexual desire (p-value = 0.040) was observed during the nut intervention. No significant differences in changes between groups were shown in peripheral concentrations of NO and E-selectin. Including nuts in a regular diet significantly improved auto-reported orgasmic function and sexual desire.


Assuntos
Valor Nutritivo , Nozes , Ereção Peniana , Comportamento Sexual , Adolescente , Adulto , Biomarcadores/sangue , Dieta Ocidental , Selectina E/sangue , Voluntários Saudáveis , Humanos , Masculino , Óxido Nítrico/sangue , Recomendações Nutricionais , Espanha , Fatores de Tempo , Adulto Jovem
10.
Sci Rep ; 9(1): 3389, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30833599

RESUMO

The aim of this cross-sectional analysis is to investigate the associations between the adherence to the Mediterranean Diet (MD) and semen quality parameters. To assess the adherence to the MD, the Trichopoulou score was used. Semen parameters were assessed as described in the 2010 WHO's report and the results are showed across tertiles of MD adherence. A total of 106 participants were included. Compared to those in the lowest MD adherence tertile, participants in the top tertile had statistically significant higher BMI and waist circumference and consumed more energy, and also had statistically significant higher semen pH, and total sperm motility and progressive sperm motility percentages, and lower sperm immotility percentages. Moreover, percentage of total and progressive motility were significantly higher among those subjects in the higher adherence to MD in comparison with those in low-medium adherence category. The multivariable linear regression models evaluating the relationship between the sperm quality parameters and tertiles of MD adherence adjusted by age, energy and BMI showed that compared with the lowest tertile, men in the highest tertile had a higher percentage of total sperm motility [ß non-standardized coefficient = 12.785]. These findings suggest that adherence to the MD was positively associated with sperm motility.

11.
Am J Clin Nutr ; 108(5): 953-962, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30475967

RESUMO

Background: Human semen quality has declined in industrialized countries. Pollution, smoking, and the consumption of a Western-style diet are all hypothesized as potential causes. Objective: We evaluated the effect of chronic consumption of nuts on changes in conventional semen parameters and the potential mechanisms implicated. Design: The FERTINUTS study was a 14-wk randomized, controlled, parallel trial. A total of 119 healthy men, aged 18-35 y, were allocated to 1 of 2 intervention groups: one group was fed the usual Western-style diet enriched with 60 g of a mixture of nuts/d (nut group), and the other was fed the usual Western-style diet avoiding nuts (control group). Semen and blood samples were collected at baseline and at the end of the intervention. Dietary information was recorded throughout the trial. Changes in conventional semen parameters (pH, volume, sperm count and concentration, motility, and morphology) were determined as primary outcomes. The effect of nut consumption on sperm DNA fragmentation (SDF), reactive oxygen species (ROS) production, chromosome anomalies (X, Y, and 18), total DNA methylation, and microRNA expression were measured in sperm samples as potential causes of the changes in the seminogram. Results: Compared with the control group, improvements in total sperm count (P = 0.002) and vitality (P = 0.003), total motility (P = 0.006), progressive motility (P = 0.036), and morphology of sperm (P = 0.008) were observed in the nut group. Participants in the nut group showed an increase in the consumption of total fat, monounsaturated fatty acids, polyunsaturated fatty acids, magnesium, vitamin E, α-linolenic acid, total omega-3 (n-3) and ω-3:ω-6 ratio intake during the intervention. Participants in the nut group showed a significant reduction in SDF (P < 0.001) and in the expression of hsa-miR-34b-3p (P = 0.036). No significant changes in ROS, sperm chromosome anomalies, or DNA methylation were observed between groups. Conclusions: The inclusion of nuts in a Western-style diet significantly improves the total sperm count and the vitality, motility, and morphology of the sperm. These findings could be partly explained by a reduction in the sperm DNA fragmentation. This trial was registered at ISRCTN as ISRCTN12857940.


Assuntos
Fragmentação do DNA , Dieta Ocidental , Comportamento Alimentar , Nozes , Contagem de Espermatozoides , Motilidade Espermática , Espermatozoides , Adolescente , Adulto , Cromossomos , Metilação de DNA , Dieta , Dieta Mediterrânea , Dieta Ocidental/efeitos adversos , Gorduras na Dieta/administração & dosagem , Ácidos Graxos Ômega-3 , Humanos , Masculino , MicroRNAs/metabolismo , Valor Nutritivo , Espécies Reativas de Oxigênio/metabolismo , Valores de Referência , Sêmen , Análise do Sêmen , Espermatozoides/fisiologia , Adulto Jovem
12.
Adv Nutr ; 9(6): 833-848, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30462179

RESUMO

Infertility, which affects ∼15% of the world's population, is a global public health issue recognized by the WHO. Therefore, it is of major clinical and public health importance to investigate whether modifiable lifestyle factors-such as stress, drug use, smoking, alcohol intake, and diet-may influence human fertility. A systematic review and meta-analysis of randomized clinical trials (RCTs) from the MEDLINE-PubMed database was conducted to assess the effect of nutrients, dietary supplements, or food on sperm quality parameters. In total, 28 articles were included for qualitative analysis and 15 for quantitative meta-analysis. Total sperm concentrations [expressed as mean differences (MDs); 95% CIs, in spermatozoa (spz)/mL] were increased by selenium (3.91 × 106 spz/mL; 3.08, 4.73 spz/mL), zinc (1.48 × 106 spz/mL; 0.69, 2.27 spz/mL), omega-3 (n-3) fatty acids (10.98 × 106 spz/mL; 10.25, 11.72 spz/mL), and coenzyme Q10 (CoQ10) (5.93 × 106 spz/mL; 5.36, 6.51 spz/mL). Sperm counts were increased by ω-3 fatty acids (18.70 × 106 spz/mL; 16.89, 20.51 spz/mL) and CoQ10 supplementation (10.15 × 106 spz/mL; 8.34, 11.97 spz/mL). Sperm total motility was increased by selenium (3.30%; 2.95%, 3.65%), zinc (7.03%; 6.03%, 8.03%), ω-3 fatty acids (7.55%; 7.09%, 8.01%), CoQ10 (5.30%; 4.98%, 5.62%), and carnitines (7.84%; 6.54%, 9.13%), whereas sperm progressive motility was increased only after supplementation with carnitines (7.45%; 6.24%, 8.67%). Finally, sperm morphology was enhanced by selenium (1.87%; 1.50%, 2.24%), ω-3 fatty acid (0.91%; 0.69%, 1.13%), CoQ10 (1.06%; 0.72%, 1.41%), and carnitine (4.91%; 3.68%, 6.15%) supplementation. This meta-analysis of RCTs suggests that some dietary supplements could beneficially modulate sperm quality parameters and affect male fertility. However, results must be cautiously interpreted due to the limited sample size of the meta-analyzed studies and the considerable observed interstudy heterogeneity.The present study and the corresponding search protocol were registered at the PROSPERO registry at http://www.crd.york.ac.uk/PROSPERO as CRD42017058380.


Assuntos
Suplementos Nutricionais , Infertilidade Masculina/terapia , Nutrientes/farmacologia , Espermatozoides/efeitos dos fármacos , Adulto , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos
14.
Epigenomics ; 9(10): 1299-1315, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28877596

RESUMO

AIM: To characterize the sperm methylome in semen samples from 19 donors with proven fertility. MATERIALS & METHODS: Bisulfite-converted sperm DNA was hybridized on the HumanMethylation450 Infinium BeadChip platform. CpG fluorescence intensities were extracted and converted to ß-values. RESULTS: The sperm methylome is highly homogeneous and hypomethylated. Genes with hypomethylated promoters are ontologically associated to biological functions related to spermatogenesis and embryogenesis. Sex chromosomes are the most hypomethylated chromosomes, supporting data that indicated their essential role in spermatogenesis. A total of 94 genes are resistant to demethylation, being strong candidates for transgenerational inheritance. CONCLUSION: Spermatozoa carry a homogeneous methylation profile that is a footprint of past events (spermatogenesis), is designed to facilitate future events (embryogenesis) and has a possible influence in the adult life (transgenerational effects).


Assuntos
Metilação de DNA , Epigênese Genética , Espermatozoides/metabolismo , Adulto , Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Ilhas de CpG , Desenvolvimento Embrionário/genética , Humanos , Masculino , Regiões Promotoras Genéticas , Espermatogênese/genética , Espermatozoides/citologia
15.
Hum Reprod Update ; 23(4): 371-389, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28333357

RESUMO

BACKGROUND: Infertility is a global public health issue, affecting 15% of all couples of reproductive age. Male factors, including decreased semen quality, are responsible for ~25% of these cases. The dietary pattern, the components of the diet and nutrients have been studied as possible determinants of sperm function and/or fertility. OBJECTIVE AND RATIONALE: Previous systematic reviews have been made of the few heterogeneous low-quality randomized clinical trials (RCTs) conducted in small samples of participants and investigating the effect of specific nutrients and nutritional supplements on male infertility. However, as yet there has been no systematic review of observational studies. SEARCH METHODS: A comprehensive systematic review was made of the published literature, from the earliest available online indexing year to November 2016, in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We have included cross-sectional, case-control and prospective and retrospective studies in which fertile/infertile men were well defined (men with sperm disorders, sperm DNA damage, varicocele or idiopathic infertility). The primary outcomes were semen quality or fecundability. With the data extracted, we evaluated and scored the quality of the studies selected. We excluded RCTs, animal studies, review articles and low-quality studies. OUTCOMES: A total of 1944 articles were identified, of which 35 were selected for qualitative analysis. Generally, the results indicated that healthy diets rich in some nutrients such as omega-3 fatty acids, some antioxidants (vitamin E, vitamin C, ß-carotene, selenium, zinc, cryptoxanthin and lycopene), other vitamins (vitamin D and folate) and low in saturated fatty acids and trans-fatty acids were inversely associated with low semen quality parameters. Fish, shellfish and seafood, poultry, cereals, vegetables and fruits, low-fat dairy and skimmed milk were positively associated with several sperm quality parameters. However, diets rich in processed meat, soy foods, potatoes, full-fat dairy and total dairy products, cheese, coffee, alcohol, sugar-sweetened beverages and sweets have been detrimentally associated with the quality of semen in some studies. As far as fecundability is concerned, a high intake of alcohol, caffeine and red meat and processed meat by males has a negative influence on the chance of pregnancy or fertilization rates in their partners. WIDER IMPLICATIONS: Male adherence to a healthy diet could improve semen quality and fecundability rates. Since observational studies may prove associations but not causation, the associations summarized in the present review need to be confirmed with large prospective cohort studies and especially with well-designed RCTs.


Assuntos
Dieta/efeitos adversos , Comportamento Alimentar , Fertilidade , Alimentos , Infertilidade Masculina/etiologia , Análise do Sêmen , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Observacionais como Assunto , Gravidez , Estudos Prospectivos , Estudos Retrospectivos
16.
Mol Hum Reprod ; 23(1): 45-53, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27932553

RESUMO

STUDY QUESTION: What is the most reliable normalization strategy for sperm microRNA (miRNA) quantitative Reverse Transcription Polymerase Chain Reactions (qRT-PCR) using singleplex assays? SUMMARY ANSWER: The use of the average expression of hsa-miR-100-5p and hsa-miR-30a-5p as sperm miRNA qRT-PCR data normalizer is suggested as an optimal strategy. WHAT IS KNOWN ALREADY: Mean-centering methods are the most reliable normalization strategies for miRNA high-throughput expression analyses. Nevertheless, specific trustworthy reference controls must be established in singleplex sperm miRNA qRT-PCRs. STUDY DESIGN, SIZE DURATION: Cycle threshold (Ct) values from previously published sperm miRNA expression profiles were normalized using four approaches: (i) Mean-Centering Restricted (MCR) method (taken as the reference strategy); (ii) expression of the small nuclear RNA RNU6B; (iii) expression of four miRNAs selected by the Concordance Correlation Restricted (CCR) algorithm: hsa-miR-100-5p, hsa-miR-146b-5p, hsa-miR-92a-3p and hsa-miR-30a-5p; (iv) the combination of two of these miRNAs that achieved the highest proximity to MCR. PARTICIPANTS/MATERIALS, SETTING, METHODS: Expression profile data from 736 sperm miRNAs were taken from previously published studies performed in fertile donors (n = 10) and infertile patients (n = 38). For each tested normalizer molecule, expression ubiquity and uniformity across the different samples and populations were assessed as indispensable requirements for being considered as valid candidates. The reliability of the different normalizing strategies was compared to MCR based on the set of differentially expressed miRNAs (DE-miRNAs) detected between populations, the corresponding predicted targets and the associated enriched biological processes. MAIN RESULTS AND THE ROLE OF CHANCE: All tested normalizers were found to be ubiquitous and non-differentially expressed between populations. RNU6B was the least uniformly expressed candidate across samples. Data normalization through RNU6B led to dramatically misguided results when compared to MCR outputs, with a null prediction of target genes and enriched biological processes. Hsa-miR-146b-5p and hsa-miR-92a-3p were more uniformly expressed than RNU6B, but their results still showed scant proximity to the reference method. The highest resemblance to MCR was achieved by hsa-miR-100-5p and hsa-miR-30a-5p. Normalization against the combination of both miRNAs reached the best proximity rank regarding the detected DE-miRNAs (Area Under the Curve = 0.8). This combination also exhibited the best performance in terms of the target genes predicted (72.3% of True Positives) and their corresponding enriched biological processes (70.4% of True Positives). LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: This study is focused on sperm miRNA qRT-PCR analysis. The use of the selected normalizers in other cell types or tissues would still require confirmation. WIDER IMPLICATIONS OF THE FINDINGS: The search for new fertility biomarkers based on sperm miRNA expression using high-throughput assays is one of the upcoming challenges in the field of reproductive genetics. In this context, validation of the results using singleplex assays would be mandatory. The normalizer strategy suggested in this study would provide a universal option in this area, allowing for normalization of the validated data without causing meaningful variations of the results. Instead, qRT-PCR data normalization by RNU6B should be discarded in sperm-miRNA expression studies. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the 2014/SGR00524 project (Agència de Gestió d'Ajuts Universitaris i de Recerca, Generalitat de Catalunya, Spain) and UAB CF-180034 grant (Universitat Autònoma de Barcelona). Celia Corral-Vazquez is a recipient of a Personal Investigador en Formació grant UAB/PIF2015 (Universitat Autònoma de Barcelona). The authors report no conflict of interest.


Assuntos
Infertilidade Masculina/genética , MicroRNAs/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , Espermatozoides/metabolismo , Adulto , Estudos de Casos e Controles , Humanos , Infertilidade Masculina/patologia , Masculino , RNA Nuclear Pequeno/genética , Padrões de Referência , Espermatozoides/patologia
17.
Reprod Biomed Online ; 33(6): 709-719, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27692602

RESUMO

The influence of aberrant sperm DNA methylation on the reproductive capacity of couples has been postulated as a cause of infertility. This study compared the DNA methylation of spermatozoa of 19 fertile donors and 42 infertile patients using the Illumina 450K array. Clustering analysis of methylation data arranged fertile and infertile patients into two groups. Bivariate clustering analysis identified a differential distribution of samples according to the characteristics of seminogram and age, suggesting a possible link between these parameters and specific methylation profiles. The study identified 696 differentially methylated cytosine-guanine dinucleotides (CpG) associated with 501 genes between fertile donors and infertile patients. Ontological enrichment analysis revealed 13 processes related to spermatogenesis. Data filtering identified a set of 17 differentially methylated genes, some of which had functions relating to spermatogenesis. A significant association was identified between RPS6KA2 hypermethylation and advanced age (P = 0.016); APCS hypermethylation and oligozoospermia (P = 0.041); JAM3/NCAPD3 hypermethylation and numerical chromosome sperm anomalies (P = 0.048); and ANK2 hypermethylation and lower pregnancy rate (P = 0.040). This description of a set of differentially methylated genes provides a framework for further investigation into the influence of such variation in male fertility in larger patient cohorts.


Assuntos
Metilação de DNA , Infertilidade Masculina/genética , Espermatogênese/genética , Espermatozoides/metabolismo , Adulto , Análise por Conglomerados , Ilhas de CpG , Feminino , Fertilidade/genética , Humanos , Masculino , Oligospermia/genética , Gravidez , Taxa de Gravidez , Regiões Promotoras Genéticas , Reprodução , Adulto Jovem
18.
Int J Mol Sci ; 17(8)2016 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-27537871

RESUMO

Recently, microRNAs (miRNA) have been proposed as regulators in the different processes involved in alcohol intake, and differences have been found in the miRNA expression profile in alcoholics. However, no study has focused on analyzing polymorphisms in genes encoding miRNAs and daily alcohol consumption at the population level. Our aim was to investigate the association between a functional polymorphism in the pre-miR-27a (rs895819 A>G) gene and alcohol consumption in an elderly population. We undertook a cross-sectional study of PREvención con DIeta MEDiterránea (PREDIMED)-Valencia participants (n = 1007, including men and women aged 67 ± 7 years) and measured their alcohol consumption (total and alcoholic beverages) through a validated questionnaire. We found a strong association between the pre-miR-27a polymorphism and total alcohol intake, this being higher in GG subjects (5.2 ± 0.4 in AA, 5.9 ± 0.5 in AG and 9.1 ± 1.8 g/day in GG; padjusted = 0.019). We also found a statistically-significant association of the pre-miR-27a polymorphism with the risk of having a high alcohol intake (>2 drinks/day in men and >1 in women): 5.9% in AA versus 17.5% in GG; padjusted < 0.001. In the sensitivity analysis, this association was homogeneous for sex, obesity and Mediterranean diet adherence. In conclusion, we report for the first time a significant association between a miRNA polymorphism (rs895819) and daily alcohol consumption.


Assuntos
Consumo de Bebidas Alcoólicas/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Estudos Transversais , Feminino , Genótipo , Humanos , Masculino , Região do Mediterrâneo , Pessoa de Meia-Idade
19.
Fertil Steril ; 104(3): 591-601, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26143365

RESUMO

OBJECTIVE: To compare the microRNA (miRNA) expression profile in spermatozoa from three infertile populations vs. a group of fertile men. DESIGN: Evaluation of the expression level of 736 miRNAs in human spermatozoa using TaqMan quantitative reverse transcription-polymerase chain reaction. SETTING: University research facility. PATIENT(S): Semen samples with a single seminal alteration were collected from infertile individuals: asthenozoospermic (n = 10), teratozoospermic (n = 10), and oligozoospermic (n = 10). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Correlation of the expression level of each miRNA with seminal parameters, age, and chromosome instability; clustering of the individuals according to their miRNA expression profiles and influence of the seminogram, age, chromosome instability, and assisted reproductive technology outcome in the clustering; analysis of the differentially expressed miRNAs (DE-miRNAs) in each infertile population; genome annotation of these DE-miRNAs; and ontological analysis of their predicted targets. RESULT(S): The hsa-miR-34b-3p correlated with age, the hsa-miR-629-3p with sperm motility, and the hsa-miR-335-5p, hsa-miR-885-5p, and hsa-miR-152-3p with sperm concentration. The individuals clustered into two groups, and only the seminogram was differentially distributed. We identified 32 DE-miRNAs in the asthenozoospermic group, 19 in the teratozoospermic group, and 18 in the oligozoospermic group. The up-regulated miRNAs presented an enriched localization in introns, affecting relevant genes for spermatogenesis. The predicted targets of the DE-miRNAs contained critical genes associated to infertility, and their ontological analysis revealed significantly associated functions related to the seminal alterations of each group. CONCLUSION(S): Spermatozoa from patients with seminal alterations exhibit a differential miRNA profile. This provides new evidence that miRNAs have an essential role in spermatogenesis, contributing to the mechanisms involved in human fertility.


Assuntos
Fertilidade/genética , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genética , MicroRNAs/genética , Espermatozoides/química , Astenozoospermia/diagnóstico , Astenozoospermia/genética , Astenozoospermia/fisiopatologia , Azoospermia/diagnóstico , Azoospermia/genética , Azoospermia/fisiopatologia , Estudos de Casos e Controles , Instabilidade Cromossômica , Análise por Conglomerados , Perfilação da Expressão Gênica/métodos , Marcadores Genéticos , Humanos , Infertilidade Masculina/fisiopatologia , Masculino , Oligospermia/diagnóstico , Oligospermia/genética , Oligospermia/fisiopatologia , Idade Paterna , Fatores de Risco , Contagem de Espermatozoides , Motilidade Espermática , Espermatozoides/patologia
20.
Fertil Steril ; 102(1): 213-222.e4, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24794309

RESUMO

OBJECTIVE: To characterize the microRNA (miRNA) expression profile in spermatozoa from human fertile individuals and their implications in human fertility. DESIGN: The expression levels of 736 miRNAs were evaluated using TaqMan arrays. Ontologic analyses were performed to determine the presence of enriched biological processes among their targets. SETTING: University research and clinical institutes. PATIENT(S): Ten individuals with normal seminogram, standard karyotype, and proven fertility. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Expression levels of 736 miRNAs, presence of enriched metabolic routes among their targets, homogeneity of the population, influence of demographic features in the results, presence of miRNA stable pairs, and best miRNA normalizing candidates. RESULT(S): A total of 221 miRNAs were consistently present in all individuals, 452 were only detected in some individuals, and 63 did not appear in any sample. The ontologic analysis of the 2,356 potential targets of the ubiquitous miRNAs showed an enrichment of processes related to cell differentiation, development, morphogenesis, and embryogenesis. None of the miRNAs were significantly correlated with age, semen volume, sperm concentration, motility, or morphology. Correlations between samples were statistically significant, indicating a high homogeneity of the population. A set of 48 miRNA pairs displayed a stable expression, a particular behavior that is discussed in relationship to their usefulness as fertility biomarkers. Hsa-miR-532-5p, hsa-miR-374b-5p, and hsa-miR-564 seemed to be the best normalizing miRNA candidates. CONCLUSION(S): Human sperm contain a stable population of miRNAs potentially related to embryogenesis and spermatogenesis.


Assuntos
Fertilidade/genética , Perfilação da Expressão Gênica , MicroRNAs/análise , Espermatogênese/genética , Espermatozoides/química , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica no Desenvolvimento , Ontologia Genética , Marcadores Genéticos , Humanos , Infertilidade Masculina/genética , Infertilidade Masculina/fisiopatologia , Masculino
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