Abstract
Graphene Oxide (GO) is a widely used biomaterial with an amazing variety of applications in biology and medicine. Recently, we reported the ability of GO to improve the in vitro fertilization (IVF) outcomes in swine, a validated animal model with a high predictive value for human fertility. For that reason, here we characterized the mechanisms involved in this positive interaction by adopting an experimental approach combining biological methods (confocal microscopy analysis on single cell, flow cytometry on cell populations and co-incubation with epithelial oviductal cells), physical-chemical techniques (Differential Scanning Calorimetry and Thermogravimetric Analysis), and chemical methods (mass spectrometry and lipid measurement). As a result, we propose a model in which GO is able to extract cholesterol from the spermatozoa membrane without causing any detrimental effect. In this way, the cholesterol extraction promotes a change in membrane chemical-physical properties that could positively affect male gamete function, modulating sperm signalling function and increasing in this way the fertilizing potential, without losing the ability to physiologically interact with the female environment. In conclusion, these data seem to suggest new intriguing possibilities in engineering sperm membrane for improving assisted reproduction technologies outcomes, even in human medicine.
Highlights
The use of biomaterials has experienced an incredible dissemination for a myriad of applications, ranging from regenerative medicine to diagnostics
After its discovery, researchers started to develop a large family of graphene-related materials, such as few layer graphene sheets (FLGS), ultrathin graphite, graphene nanosheets, graphene oxide (GO), and reduced graphene oxide, with a wide range of applications in electronic, engineering, chemistry, and
The presence of Ca2+ and bicarbonate activates a cAMP/ PKA-dependent pathway that leads to the rupture of membrane asymmetry with the consequent exposure of cholesterol on the outer side of plasma membrane (PM)[23,24,25,26,27,28,29,30,31,32,33]
Summary
The use of biomaterials has experienced an incredible dissemination for a myriad of applications, ranging from regenerative medicine to diagnostics. At relatively high concentrations (10 and 50 μg/ml), it was able to induce a toxic damage expressed as decreased viability and loss of acrosome integrity, while in a definite range of concentrations (0.5 to 1 μg/mL), surprisingly, GO seemed to promote the fertilizing ability in an in vitro fertilization (IVF) assay[20] Since this unexpected effect could be interesting either for the understanding of the basics GO interaction with living systems as well as for the development of possible technological applications in assisted reproduction technologies (ARTs), here we carried out further experiments by combining biological, chemical and physical approaches, with the aim of exploring the molecular mechanisms of this interaction
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