Abstract
Currently, even the most sophisticated methods of assisted reproductive technology (ART) allow us to achieve live births in only approximately 30% of patients, indicating that our understanding of the fine mechanisms underlying reproduction is far from ideal. One of the main challenges associated with studies of gamete structure and function is that these cells are remarkably resistant towards the uptake of exogenous substances, including 'molecular research tools' such as drugs, biomolecules and intracellular markers. This phenomenon can affect not only the performance of reproductive biology research techniques, but also the outcomes of the in vitro handling of gametes, which forms the cornerstone of ART. Improvement of intra-gamete delivery in a non-aggressive fashion is vital for the investigation of gamete physiology, and the advancement of infertility treatment. In this review, we outline the current state of nanomaterial-mediated delivery into gametes and embryos in vitro, and discuss the potential of a novel exciting drug delivery technology, based upon the use of targeted 'natural' nanoparticles known as extracellular vesicles (EVs), for reproductive science and ART, given the promising emerging data from other fields. A comprehensive electronic search of PubMed and Web of Science databases was performed using the following keywords: 'nanoparticles', 'nanomaterials', 'cell-penetrating peptides', 'sperm', 'oocyte', 'egg', 'embryo', 'exosomes', 'microvesicles', 'extracellular vesicles', 'delivery', 'reproduction', to identify the relevant research and review articles, published in English up to January 2015. The reference lists of identified publication were then scanned to extract additional relevant publications. Biocompatible engineered nanomaterials with high loading capacity, stability and selective affinity represent a potential versatile tool for the minimally invasive internalization of molecular cargo into gametes and embryos. However, it is becoming increasingly clear that the translation of these experimental tools into clinical applications is likely to be limited by their non-biodegradable nature. To allow the subsequent use of these methodologies for clinical ART, studies should utilize biodegradable delivery platforms, which mimic natural mechanisms of molecular cargo trafficking as closely as possible. Currently, EVs represent the most physiological intracellular delivery tools for reproductive science and medicine. These natural mediators of cell communication combine the benefits of engineered nanomaterials, such as the potential for in vitro production, targeting and loading, with the essential feature of biodegradability. We anticipate that future investigations into the possibility of applying EVs for the intentional intracellular delivery of molecular compounds into gametes and embryos will open new horizons for reproductive science and clinical ART, ultimately leading to improvements in patient care.
Highlights
Introduction BackgroundResearch into the mechanisms of gamete function: current challenges
From a rather more applied perspective, tools for efficient and nondamaging intra-gamete delivery could hold a therapeutic promise for patients with infertility caused by specific molecular deficiencies in gametes, for example deficiency of the sperm-borne oocyte-activating factor phospholipase C zeta (PLCz), resulting in oocyte activation failure post-fertilization, even following the intracytoplasmic injection of sperm into oocytes (ICSI) (Amdani et al, 2013)
A comprehensive electronic search of PubMed (US National Library of Medicine, National Institute of Health; http://www.ncbi.nlm.nih.gov/pubmed/) and Web of Science (Thomson Reuters, http://webofknowledge.com/) databases was performed using the following keywords: ‘nanoparticles’, ‘nanomaterials’, ‘cell-penetrating peptides’, ‘sperm’, ‘oocyte’, ‘egg’, ‘embryo’, ‘exosomes’, ‘microvesicles’, ‘extracellular vesicles’, ‘delivery’, ‘reproduction’ to identify the relevant research and review articles published in English up to January 2015
Summary
Assisted reproductive technology (ART) has revolutionized the field of infertility treatment, resulting in the birth of .5 million children worldwide ever since its first successful use in humans in 1978 (Adamson et al, 2013). From a rather more applied perspective, tools for efficient and nondamaging intra-gamete delivery could hold a therapeutic promise for patients with infertility caused by specific molecular deficiencies in gametes, for example deficiency of the sperm-borne oocyte-activating factor PLCz, resulting in oocyte activation failure post-fertilization, even following the intracytoplasmic injection of sperm into oocytes (ICSI) (Amdani et al, 2013) These tools could be used in applied ART to supplement gametes with fertility-enhancing compounds, either promoting sperm motility or protecting gametes from deterioration during long-term culture in vitro (Kawamura et al, 2012; Yun et al, 2013; Tardif et al, 2014), especially for such indications as the in vitro maturation of oocytes or the in vitro culture of oocytes from primordial follicles for experimental fertility preservation programmes (Telfer and McLaughlin, 2012). We outline the current state of nanomaterial-mediated delivery into gametes and embryos in vitro, and discuss the potential of a novel exciting drug delivery technology, based upon the use of targeted ‘natural’ nanoparticles, known as extracellular vesicles (EVs), for reproductive science and ART, given the promising emerging data from other fields
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
