Dieta iperlipidica e infertilità maschile: ruolo degli acidi grassi saturi sul metabolismo energetico degli spermatozoi

L’assunzione di una dieta iperlipidica, caratterizzata da un elevato contenuto in acidi grassi saturi e monoinsaturi e priva di acidi grassi polinsaturi della serie ω-3 ha causato, in modelli animali, obesità, insulino-resistenza, dislipidemie e, parallelamente, una riduzione della qualità spermatica in termini di decremento della concentrazione e della motilità dei gameti maschili. Un’approfondita analisi dei meccanismi molecolari che sono alla base di tale effetto ha evidenziato la presenza di difetti nel metabolismo energetico, riguardanti sia la glicolisi che i processi mitocondriali responsabili della produzione di ATP. Pertanto, l’impiego di nuove strategie terapeutiche, quali la restrizione calorica o l’integrazione con acidi grassi polinsaturi, che regolano la funzione e la biogenesi mitocondriale, potrebbe avere un enorme potenziale preventivo e/o terapeutico anche nel trattamento dell’infertilità maschile

Obesity and Male Infertility: Role of Fatty Acids in the Modulation of Sperm Energetic Metabolism

Obesity in men of reproductive age is increasing worldwide, impacting negatively on reproductive potential, sperm function, and assisted reproduction outcomes. Changes in modern eating behaviors are needed to invert the negative correlation between lifestyle and sperm quality. It is known from the literature that fatty acids are able to modulate lipid metabolism by complex mechanisms involving a sequence of interdependent and cross-regulated molecular events. Although a great deal of data is currently available on the dietary modulation of lipid metabolism, little is known about the nutritional regulation of sperm energetic metabolism. In this review, major data from the literature about the role of some dietary fats as modulators of sperm function and quality are described. Moreover, biochemical mechanisms responsible for an impairment or improvement in sperm bioenergetics are critically analyzed. It is noteworthy that both quantitative and qualitative aspects of dietary fats influence sperm function. The administration of a high-fat diet, low in polyunsaturated fatty acids, caused a significant increase in body weight hyperglycemia, hyperinsulinemia, and dyslipidemia, along with a significant reduction in sperm quality. In contrast, unsaturated fatty acids are able to positively influence sperm quality and function. The understanding of the biochemical mechanisms underlying the development of male infertility related to obesity led us to depict a possible framework for the molecular action of fatty acids on sperm quality during dysmetabolic conditions

Comparative ProteomicAnalysis of Proteins Involved in Bioenergetics Pathways Associated with Human Sperm Motility

none8Sperm motility is the most important parameter involved in the fertilization process and it is strictly required for the reproductive success. Although sperm movements are essential for the physiologic fertilization process, the data, deriving from studies focused on the research of altered cell pathways involved in asthenozoospermia, offer only limited information about molecular mechanism underlying sperm motility. The aim of this study was to identify proteins involved in human sperm motility deficiency by using LC−MS/MS. For this purpose, we selected sperm samples with three different classes of progressive motility: low, medium (asthenozoospermic samples) and high (normozoospermic samples). We found that several differential expressed proteins in asthenozoospermic samples were related to energetic metabolism, suggesting an interesting link between bioenergetics pathways and the regulation of sperm motility, necessary for the flagellum movement. Therefore, our results provide strong evidence that mass spectrometry-based proteomics represents an integrated approach to detect novel biochemical markers of sperm motility and quality with diagnostic relevance for male infertility and unravel the molecular etiology of idiopathic cases.mixedMoscatelli, Natalina; Lunetti, Paola; Braccia, Clarissa; Armirotti, Andrea; Pisanello, Ferruccio; De Vittorio, Massimo; Zara, Vincenzo; Ferramosca, Alessandra.Moscatelli, Natalina; Lunetti, Paola; Braccia, Clarissa; Armirotti, Andrea; Pisanello, Ferruccio; De Vittorio, Massimo; Zara, Vincenzo; Ferramosca, Alessandra

Single-cell-based evaluation of sperm progressive motility via fluorescent assessment of mitochondria membrane potential

Sperm cells progressive motility is the most important parameter involved in the fertilization process. Sperm middle piece contains mitochondria, which play a critical role in energy production and whose proper operation ensures the reproductive success. Notably, sperm progressive motility is strictly related to mitochondrial membrane potential (MMP) and consequently to mitochondrial functionality. Although previous studies presented an evaluation of mitochondrial function through MMP assessment in entire sperm cells samples, a quantitative approach at single-cell level could provide more insights in the analysis of semen quality. Here we combine laser scanning confocal microscopy and functional fluorescent staining of mitochondrial membrane to assess MMP distribution among isolated spermatozoa. We found that the sperm fluorescence value increases as a function of growing progressive motility and that such fluorescence is influenced by MMP disruptors, potentially allowing for the discrimination of different quality classes of sperm cells in heterogeneous populations

Chemical Control of FGF-2 Release for Promoting Calvarial Healing with Adipose Stem Cells*

Chemical control of protein secretion using a small molecule approach provides a powerful tool to optimize tissue engineering strategies by regulating the spatial and temporal dimensions that are exposed to a specific protein. We placed fibroblast growth factor 2 (FGF-2) under conditional control of a small molecule and demonstrated greater than 50-fold regulation of FGF-2 release as well as tunability, reversibility, and functionality in vitro. We then applied conditional control of FGF-2 secretion to a cell-based, skeletal tissue engineering construct consisting of adipose stem cells (ASCs) on a biomimetic scaffold to promote bone formation in a murine critical-sized calvarial defect model. ASCs are an easily harvested and abundant source of postnatal multipotent cells and have previously been demonstrated to regenerate bone in critical-sized defects. These results suggest that chemically controlled FGF-2 secretion can significantly increase bone formation by ASCs in vivo. This study represents a novel approach toward refining protein delivery for tissue engineering applications