Graphene Oxide Improves in vitro Fertilization in Mice With No Impact on Embryo Development and Preserves the Membrane Microdomains Architecture

Nicola Bernabò,Serena Pilato,Marina Ramal-Sanchez,Paola Palestini,Luca Valbonetti,Martin Fray,Ferdinando Scavizzi,Susan Allen,Marcello Raspa,Renata Paoletti,Barbara Barboni,Juliana Machado-Simoes,Antonella Fontana,Laura Botto

doi:10.3389/fbioe.2020.00629

Abstract

During the latest years, human infertility worsened all over the world and is nowadays reputed as a global public health issue. As a consequence, the adoption of Assisted Reproductive Technologies (ARTs) such as In Vitro Fertilization (IVF) is undergoing an impressive increase. In this context, one of the most promising strategies is the innovative adoption of extra-physiological materials for advanced sperm preparation methods. Here, by using a murine model, the addition of Graphene Oxide (GO) at a specific concentration has demonstrated to increase the spermatozoa fertilizing ability in an IVF assay, finding that 0.5 μg/ml GO addition to sperm suspensions before IVF is able to increase both the number of fertilized oocytes and embryos created with a healthy offspring given by Embryo Transplantation (ET). In addition, GO treatment has been found more effective than that carried out with methyl-β-cyclodextrin, which represents the gold standard in promoting in vitro fertility of mice spermatozoa. Subsequent biochemical characterization of its interaction with male gametes has been additionally performed. As a result, it was found that GO exerts its positive effect by extracting cholesterol from membranes, without affecting the integrity of microdomains and thus preserving the sperm functions. In conclusion, GO improves IVF outcomes in vitro and in vivo, defining new perspectives for innovative strategies in the treatment of human infertility.

Highlights

In the recent years, our society has witnessed a concerning decay of human fertility, as claimed by the WHO (Mascarenhas et al, 2012) and the European in vitro fertilization (IVF)-Monitoring Consortium (EIM), group of the European Society of Human Reproduction and Embryology (ESHRE) (De Geyter et al, 2018)
The use of Assisted Reproduction Technology (ART) as a specific therapeutic strategy has been characterized by an impressive increase since 1978 with the birth of Louise Brown, the first baby conceived by in vitro fertilization (IVF) in the world and, more recently, thanks to the awarded of Nobel prize in Physiology or Medicine for the development of Human In Vitro Fertilization (Edwards, 2001)
We found that the co-incubation of capacitating spermatozoa with a specific concentration of graphene oxide (GO) (0.5 μg/ml) was able to increase the number of both fertilized oocytes and developed embryos/birth rates without exerting toxic collateral effects

Summary

Introduction

Our society has witnessed a concerning decay of human fertility, as claimed by the WHO (Mascarenhas et al, 2012) and the European IVF-Monitoring Consortium (EIM), group of the European Society of Human Reproduction and Embryology (ESHRE) (De Geyter et al, 2018). Graphene Oxide Improves Mice IVF a pregnancy over 12 months of regular and unprotected sexual intercourse (Barratt et al, 2017). This medical condition affects approximately 15–20% (48.5 million) of the couples worldwide (Mascarenhas et al, 2012). The use of Assisted Reproduction Technology (ART) as a specific therapeutic strategy has been characterized by an impressive increase since 1978 with the birth of Louise Brown, the first baby conceived by in vitro fertilization (IVF) in the world and, more recently, thanks to the awarded of Nobel prize in Physiology or Medicine for the development of Human In Vitro Fertilization (Edwards, 2001). It is important to mind that, as reported by the Grand View Research Incorporation1 “the global assisted reproductive technology (ART) market is expected to reach USD 45.4 billion by 2025.”

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