Abstract
Despite recent advances in male reproductive health research, there remain many elements of male infertility where our understanding is incomplete. Consequently, diagnostic tools and treatments for men with sperm dysfunction, other than medically assisted reproduction, are limited. On the other hand, the gaps in our knowledge of the mechanisms which underpin sperm function have hampered the development of male non-hormonal contraceptives. The study of mature spermatozoa is inherently difficult. They are a unique and highly specialised cell type which does not actively transcribe or translate proteins and cannot be cultured for long periods of time or matured in vitro. One large-scale approach to both increasing the understanding of sperm function and the discovery and development of compounds that can modulate sperm function is to directly observe responses to compounds with phenotypic screening techniques. These target agnostic approaches can be developed into high-throughput screening platforms with the potential to drastically increase advances in the field. Here, we discuss the rationale and development of high-throughput phenotypic screening platforms for mature human spermatozoa and the multiple potential applications these present, as well as the current limitations and leaps in our understanding and the capabilities needed to overcome them. Further development and use of these technologies could lead to the identification of compounds which positively or negatively affect sperm cell motility or function or novel platforms for toxicology or environmental chemical testing among other applications. Ultimately, each of these potential applications is also likely to increase the understanding within the field of sperm biology.
Highlights
There have been several significant developments in male reproductive health that have increased our understanding of basic mechanisms and opened exciting areas of research
One is uncovering how epigenetic modification of the paternal gamete can potentially have profound effects on the health of subsequent generations (Bodden et al 2020, Lismer et al 2021). Another is understanding how male reproductive health is increasingly viewed as a sentinel marker for somatic health issues (Choy & Eisenberg 2018, Del Giudice et al 2021) and the health of subsequent offspring (Kasman et al 2020)
A plethora of studies demonstrate that our understanding of the physiology of the mature human spermatozoon is quite limited and that this is a significant roadblock to the development of badly needed diagnostic and therapeutic tools (Barratt et al 2017, 2021, De Jonge & Barratt 2019, Schlegel et al 2021)
Summary
There have been several significant developments in male reproductive health that have increased our understanding of basic mechanisms and opened exciting areas of research. One is uncovering how epigenetic modification of the paternal gamete can potentially have profound effects on the health of subsequent generations (Bodden et al 2020, Lismer et al 2021) Another is understanding how male reproductive health is increasingly viewed as a sentinel marker for somatic health issues (Choy & Eisenberg 2018, Del Giudice et al 2021) and the health of subsequent offspring (Kasman et al 2020). There are two key areas where progress remains limited, namely (i) the diagnosis of and non-medically assisted reproduction (MAR) treatment of men with sperm dysfunction; (ii) development of new male contraceptives. This review outlines these two areas including discussing the driving requirement for progress.
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