Nanomedicine and mammalian sperm: Lessons from the porcine model

Abstract

Biomedical nanotechnology allows us to engineer versatile nanosized platforms that are comparable in size to biological molecules and intracellular organelles. These platforms can be loaded with large amounts of biological cargo, administered systemically and act at a distance, target specific cell populations, undergo intracellular internalization via endogenous uptake mechanisms, and act as contrast agents or release cargo for therapeutic purposes. Over recent years, nanomaterials have been increasingly viewed as favorable candidates for intragamete delivery. Particularly in the case of sperm, nanomaterial-based approaches have been shown to improve the efficacy of existing techniques such as sperm-mediated gene transfer, loading sperm with exogenous proteins, and tagging sperm for subsequent sex- or function-based sorting. In this short review, we provide an outline of the current state of nanotechnology for biomedical applications in reproductive biology and present highlights from a series of our studies evaluating the use of specialized silica nanoparticles in boar sperm as a potential delivery vehicle into mammalian gametes. The encouraging data obtained already from the porcine model in our laboratory have formed the basis for ethical approval of similar experiments in human sperm, thereby bringing us a step closer toward the potential use of this novel technology in the clinical environment.

Applications of omics and nanotechnology to improve pig embryo production in vitro

“…Although mice have been the model of choice for most ART studies, there has been a tendency to use bull and boar sperm to evaluate nanomaterial delivery efficiency and effects. Bull and boar sperm, as human sperm, do not need to be surgically retrieved and present similarities regarding morphology and maturation profiles (Barkalina et al, ). Characterization of sperm and identification of potential targets, such as proteins related to acrosome integrity (Cross & Watson, ) and genes linked to freezability (Vilagran et al, ), make the use of nanoparticles interesting for applications in studies involving sperm enrichment and sorting (Feugang, ).…”

“…Mesoporous silica, quantum dots, iron oxide, zinc oxide, gold, and silver nanostructures have been shown to interact with cattle, human, mouse, and pig spermatozoa (Barkalina, Jones, Kashir, et al, ; Feugang et al, ; Feugang, Youngblood, Greene, Willard, & Ryan, ; Moretti et al, ; Taylor et al, ; Yoisungnern et al, ). In the pig, Barkalina et al () observed that mesoporous silica nanoparticles (MSNPs) functionalized with polyethileneimine (PEI) and aminopropyltriethoxysilane were able to stably bind one in five boar sperm with no negative effects on the main parameters of sperm function (total and progressive motility, motion parameters, viability, acrosome morphology, or DNA fragmentation index). Moreover, MSNPs loaded with proteins or nucleic acids were able to bind to the boar sperm and to the zona pellucida of mouse oocytes, demonstrating their potential for intracellular delivery.…”

“…These systems are able to pass through biological barriers and target selected pathways (Barkalina, Jones, Kashir, et al, 2014). The growing number of nanomaterials exhibiting biocompatibility with gametes and embryos have created diverse applications for the reproductive field (Barkalina, Jones, & Coward, 2016;Kim et al, 2018;Remião et al, 2017). Besides the use as nanocarriers for intragamete/embryo delivery of supplements, other significant applications of nanotechnology to the swine industry and biomedical science could be the delivery of exogenous DNA to sperm cells (Barkalina et al, 2016;Campos et al, 2011) and the delivery of Cas9 or sgRNA plasmids for gene editing (Wang et al, 2018).…”

“…It was observed that the 3D culture system enhanced development of secondary follicles when compared to a two-dimensional control treatment (follicles individually culture in 24-well plate). Also, after in vitro maturation, the 3D system improved oocyte viability and meiotic resumption when compared to the control group (Antonino et al, 2019 do not need to be surgically retrieved and present similarities regarding morphology and maturation profiles (Barkalina et al, 2016). Characterization of sperm and identification of potential targets, such as proteins related to acrosome integrity (Cross & Watson, 1994) and genes linked to freezability (Vilagran et al, 2015), make the use of nanoparticles interesting for applications in studies involving sperm enrichment and sorting (Feugang, 2017).…”

Will AI in pigs become more efficient?

“…Exosomes, small extracellular membrane vesicles modulating cellular functionality, also deserve future attention, as they are substantially present in SP. It is speculated that exosomes secreted by the male reproductive tract play important roles in promoting and regulating sperm motility, protecting the sperm in the female genital tract and facilitating fertilizing ability [59].…”