Development of nanoparticle-mediated delivery tools to investigate the role of molecular genetic mechanisms underlying male infertility

Male factor infertility is a complex disorder, affecting approximately 10-15% of couples worldwide, however many of its aetiologies are unknown [1,2]. With the advent of assisted reproductive technology (ART), men with sub-optimal sperm quality are now able to overcome natural selection mechanisms and produce viable offspring [3]. Since ART is a relatively new phenomenon, the impact of inheritance and the frequency of mutations or altered gene expression is not yet fully understood, and there are concerns that ART may conceal reproductive defects that could have negative consequences at the epigenetic level [46]. Comprehending the genetic foundation of male infertility has large implications for both understanding the underlying cause of infertility as well as determining the prognosis for patients. Mounting evidence from investigations into the specific mechanisms underlying reproduction suggests an association between abnormal gene expression/genetic polymorphisms and various forms of previously unexplained states of infertility, such as gonadal insufficiency [7] and fertilization failure [8]. Consequently, efficient targeted gene transfer into gametes, embryos, and reproductive tissues would be a powerful tool with which to manipulate and study specific mechanisms underlying infertility. With the increased prevalence of ART treatments worldwide, it is necessary to develop efficient tools for research into idiopathic infertility. Elucidating the underlying genetic causes of infertility will aid in discovering their origin and determine effective treatments for patients. In this review, we discuss important aspects of genetic male infertility, describe research advances in the development of engineered sperm constructs as research tools and to combat genetic abnormalities, as well as highlight the promising development of mesoporous silica nanoparticles as a powerful noninvasive tool to engineer sperm.