Evaluación de la expresión de Ccna1, Cyp17, StAR y Prm2 en la espermatogénesis de ratones Swiss Rockefeller tratados con Lepidium meyenii Walp. (maca)

Lepidium meyenii Walp (maca) (Brassicaceae), es empleada tradicionalmente por sus diversas propiedades, entre las que destacan la mejora en el desempeño sexual en humanos, ratas y ratones, además de mejorar la espermatogénesis. Sin embargo, el mecanismo de como la maca influye sobre la espermatogénesis es aún desconocido En el presente estudio, ratones machos de edad adulta fueron tratados con el extracto acuoso de maca, durante periodos de 7, 14 y 21 días; al final de cada tratamiento se midieron los pesos, concentración espermática y se evaluó la expresión de ciclina A1 (Ccna1), citocromo P450 17α-hidroxilasa/17,20-liasa (Cyp17), protamina 2 (Prm2) y la proteína reguladora de esteroidogénesis aguda (StAR), genes involucrados en el proceso de espermatogénesis. En los resultados se observó que la maca incrementó significativamente (p menos 0.05) la concentración espermática en los 3 grupos tratados; además la expresión de los genes Ccna1, Cyp17 y Prm2 no fue afectada significativamente a diferencia de StAR, que muestra una regulación negativa en su expresión en los grupos de 7 y 14 días de tratamiento. Estos resultados sugieren que el mecanismo por el cual la maca incrementa la concentración espermática, no está relacionado al incremento de la actividad meiótica, ni a la síntesis de testosterona, sino mas bien a la respuesta de algún componente con actividad androgénica presente en el extracto acuoso de maca, evidenciado por el efecto negativo sobre la expresión de StAR. Estos resultados revalidan la importancia de maca como potenciador reproductivo, sin el riesgo del incremento de andrógenos, contraindicados para los casos de cáncer de próstata.Lepidium meyenii Walp. (maca) (Brassicaceae) is widely used as a folk medicine, for the ability to enhance the sexual performance in humans, rats and mice, besides to improve the spermatogenesis. However, the way maca acts on spermatogenesis still unclear. In this study, adult male mice were treated with maca aqueous extract during periods of 7, 14 and 21 days, after each treatment, physiological parameters were measured and the expression of cyclin A1 (Ccna1), cytochrome P450 17α-hydroxylase/17,20-lyase (Cyp17), protamine 2 (Prm2) and steroidogenic acute regulatory protein (StAR) (genes involved in spermatogenesis), were recorded. The results shows that maca increased significantly (p less than 0.05) sperm concentration in the three treatment groups, plus Ccna1, CYP17 and Prm2 expression were not significantly affected, while StAR, shows a negative regulation on their expression in groups of 7 and 14 days of treatment. These results suggest, that the mechanism maca increases sperm concentration is not related to increased meiotic activity, or the synthesis of testosterone, but rather the response of a component with androgenic activity present in the aqueous extract of maca, evidenced by the negative effect on StAR expression. These results re-enact the importance of maca as reproductive enhancer without running the risk of increased androgen contraindicated in cases of prostate cancer.Tesi

Efecto de la solucion acuosa de "mashua" en la capacidad reproductiva de mus musculus machos y su implicancia en el desarrollo embrionario preimplantacional. Prueba preclínica: Effect of the aqueous solution of "mashua" on the reproductive capacity of male mus musculus and its implication in preimplantation embryonic development. Preclinical test

The "mashua", Tropaeolum tuberosum Ruiz & Pavón, 1802 is a plant species native from Peru and a resource of great nutritional value. In addition, there are several investigations carried out in the last decade in which its effects on mammal fertility have been verified. In this work, we evaluate the effect of the aqueous extract of T. tuberosum on the development of the preimplantation embryos of Mus musculus. The aqueous extract was administered ad libitum, in a concentration of 50 g / Kg of body weight, to three groups of mice (n = 24) during 8, 16 and 35 days; the control group drank only tap water. Each group of males were crossed with females of fertile age, the presence of a vaginal plug indicated the 0th day of embryonic development. At 72 h the uterine horns were perfused and the stage of development, condition and embryonic morphology were evaluated. Differences were found between the control and treatment groups. Our results demonstrate that the aqueous extract of T. tuberosum alters the quality of the mouse sperm, affecting the ability of the embryo to develop normally to the blastocyst stage.La "mashua", Tropaeolum tuberosum, es una especie vegetal nativa del Perú y un recurso de gran valor nutricional. Además, son varias las investigaciones realizadas en la última década en las cuales se ha comprobado sus efectos sobre la fertilidad de mamíferos. Objetivo: evaluar el efecto del extracto acuoso de T. tuberosum en el desarrollo de los embriones preimplantacionales de Mus musculus. Métodos; Se administró el extracto acuoso ad libitum, en una concentración de 50 g/Kg de peso corporal a tres grupos de ratones (n=32 – 8 por grupo caso y 7 control) durante 8, 16 y 35 días; el grupo control tomo solo agua. Cada grupo de machos se cruzaron con hembras de edad fértil, la presencia de tapón vaginal nos indicaba el día 0 de desarrollo embrionario. A las 72 h se perfusionaron los cuernos uterinos y se evaluó el grado de desarrollo, condición y morfología embrionarias. Resultados: Se encontraron diferencias entre los grupos control y tratamiento. Discusión: Nuestros resultados demuestran que el extracto acuoso de T. tuberosum altera la calidad del espermatozoide de ratón afectando la capacidad del embrión para desarrollarse normalmente hasta el estadio de blastocisto.&nbsp

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Efecto de Tropaeolum Tuberosum "Mashua" (Tropaeolaceae) sobre la expresión génica relacionada a Espermatogénesis en ratón: Effect of Tropaeolum Tuberosum "Mashua" (Tropaeolaceae) on gene expression related to spermatogenesis in mouse

Introduction: Tropaeolum tuberosum, known as "mashua" is an Andean tuber that holds both economic and nutritional value for low-income populations. It is believed that it affects male fertility because Andean men associate it with impotence and decreased fertility. Studies conducted on rats fed with "mashua" showed that there was a 45% decrease in the testosterone/dihydrotestosterone ratio. The effect of this plant on reproduction is related to its content of isothiocyanates, compounds that covalently bind to proteins, which may be directly or indirectly involved in the spermatogenic process. The purpose of this research was to evaluate the effect of the aqueous extract of "mashua" on spermatogenesis and reproductive physiology of mice. Methodology: In vivo morphofunctional parameters of mouse sperm (spermatogram) were evaluated and the expression of Cytochrome P450 17α-hydroxylase/17,20-lyase, acute steroidogenesis regulatory protein, cyclin, and protamine related to spermatogenesis was quantified. Results: The results indicated that at 7, 14 and 21 days of dosing, the sperm count was affected, as well as their progressive motility (PM), on the other hand, a delay in their maturation was observed. Regarding gene expression, no significant differences were found between the expression of the two genes studied (Cytochrome P450 17α-hydroxylase/17,20-lyase, Cyclin), Conclusion: The effect of "mashua" does not occur at the level of gene expression involved in spermatogenesis, but at the level of its functions as a protein.Introducción: Tropaeolum tuberosum, conocido como mashua, es un tubérculo andino que tiene un valor tanto económico como nutritivo para las poblaciones de pocos recursos. Se cree que afecta la fertilidad masculina, porque los hombres andinos lo relacionan con impotencia y disminución de la capacidad fecundante. Estudios hechos en ratas que se alimentaron con mashua demostraron que hubo un 45% de decrecimiento de la tasa testosterona/dihidrotestosterona. El efecto de esta planta en la reproducción está relacionada a su contenido de isotiocianatos, compuestos que se unen covalentemente a las proteínas, las cuales pueden estar directa o indirectamente involucradas en el proceso espermatogénico. El propósito de esta investigación fue evaluar el efecto del extracto acuoso de la mashua sobre la espermatogénesis y la fisiología reproductiva de ratones. Metodología: Se evaluaron los parámetros morfofuncionales in vivo de espermios de ratones (espermatograma) y se cuantificó la expresión de: Cytochrome P450 17α-hydroxylase/17,20-lyase, proteína reguladora de esteroidogenesis aguda, ciclina y protamina, relacionados a la espermatogénesis. Resultados: A los 7, 14 y 21 días de dosificación, se vio afectado el conteo de espermatozoides, así como su motilidad progresiva (MP); por otra parte, se observó un retardo en la maduración de los mismos. En cuanto a la expresión génica, no se encontró diferencias significativas entre la expresión de los dos genes estudiados (cytochrome P450 17α-hydroxylase/17,20-lyase, ciclina), Conclusión: El efecto de la mashua no se da a nivel de la expresión de los genes involucrados en la espermatogénesis, sino a nivel de sus funciones como proteína