title: Red wine consumption may affect sperm biology: the effects of different concentrations of the phytoestrogen myricetin on human male gamete function.
abstract: Myricetin is a natural flavonoid, particularly enriched in red wines, whose occurrence is widespread among plants. Despite extensive research, the beneficial effects of Myricetin on human health are still controversial. Here, we tested the estrogen-like effect of the phytoestrogen Myricetin on human ejaculated sperm biology. To this aim, human normozoospermic samples were exposed to increasing concentrations (10 nM, 100 nM, and 1 µM) of Myricetin. Motility, viability, capacitation-associated biochemical changes (i.e., cholesterol efflux and tyrosine phosphorylation), acrosin activity, as well as glucose utilization and fatty-acid oxidation (i.e., glucose and lipid metabolism) were all significantly increased by low doses of Myricetin. Importantly, both estrogen receptors α and β (ERs) and phosphatidylinositol-3-OH kinase (PI3K)/AKT signaling are activated in the presence of Myricetin since these were both abrogated by specific inhibitors of each pathway. Our results show how Myricetin, through ERs and PI3K/AKT signalings, potentiates sperm function. This effect is dose-dependent at low concentrations of Myricetin (up to 100 nM), whereas higher amounts do not seem to improve any further sperm motility, viability, or other tested features, and, in some cases, they reduced or even abrogated the efficacy exerted by lower doses. Further studies are needed to elucidate if high levels of Myricetin, which could be attained even with moderate wine consumption, could synergize with endogenous estrogens in the female reproductive tract, interfering with the physiological sperm fertilization process.
authors.affiliation: Pharmaco-Biology Department, Faculty of Pharmacy and of Nutrition and Health Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: Saveria
authors.initials: S
authors.lastname: Aquila
authors.forename: Marta
authors.initials: M
authors.lastname: Santoro
authors.forename: Francesca
authors.initials: F
authors.lastname: De Amicis
authors.forename: Carmela
authors.initials: C
authors.lastname: Guido
authors.forename: Daniela
authors.initials: D
authors.lastname: Bonofiglio
authors.forename: Marilena
authors.initials: M
authors.lastname: Lanzino
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cesario
authors.forename: Ida
authors.initials: I
authors.lastname: Perrotta
authors.forename: Diego
authors.initials: D
authors.lastname: Sisci
authors.forename: Catia
authors.initials: C
authors.lastname: Morelli
mesh_terms: D000176:Acrosin / Q000378:metabolism; D000704:Analysis of Variance; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000032:analysis / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D048789:Phytoestrogens / Q000032:analysis / Q000494:pharmacology*; D013075:Sperm Capacitation / Q000187:drug effects; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology*; D014920:Wine / Q000032:analysis*
chemical_list: D005227:Fatty Acids; D005419:Flavonoids; D048789:Phytoestrogens; C040015:myricetin; D019869:Phosphatidylinositol 3-Kinases; D000176:Acrosin; D005947:Glucose