20% of infertile cases remain unexplained and could be attributed to as yet undetermined deficiency in sperm function
Our research explores sperm development, structure and function. Our overarching aim is to improve our understanding of the processes of sperm formation and function using a variety of laboratory techniques and models.
SPERM DEVELOPMENT AND FUNCTION
Phospholipase C zeta (PLCζ), a sperm-specific protein responsible for activating the oocyte at fertilization
Activation of the oocyte at fertilization is a fundamental developmental event and in mammals is associated with a critical rise in intracellular egg calcium that manifests as a series of characteristic oscillations. Current research strongly suggests that the protein responsible is a sperm-specific phospholipase C with distinctive properties, PLCζ. We investigate how the expression, structure, and function of this, and other sperm proteins, might influence fertility.
We investigate how PLCζ, and other sperm proteins interacting with the oocyte at fertilisation, might be related to certain types of male infertility including oocyte activation deficiency, total fertilisation failure, or recurrent ICSI failure. We are also investigating the potential role of other proteins inside the oocyte that might interact with PLCζ and other sperm proteins, in order to induce activation. This work aims to develop new diagnostic tests and therapeutic strategies.
Nanoparticle- and exosome-mediated delivery systems for mammalian sperm.
Currently, artificial reproductive technology (ART) remains the gold standard for human infertility treatment and involves the complex laboratory micromanipulation of sperm and oocytes to create an embryo in vitro which is then transferred back to the mother’s uterus for implantation. However, success rates rarely exceed 35%; consequently, there is a significant need for basic scientific research to address this inefficiency and translate improvements in methodology, diagnosis and therapy back into the clinical embryology laboratory.
It may be possible to treat certain infertile conditions by delivering a therapeutic agent directly into pre-selected oocytes or sperm prior to fertilization, or even to the embryo prior to implantation. However, there are no efficient techniques at present that can ‘treat’ poor quality gametes or embryos by delivering therapeutic compounds aimed to augment or suppress physiological function. This is because these specialized cells are highly resistant to the uptake of exogenous compounds. Existing technologies all involve some form of chemical, electrical or invasive treatment, which may cause further iatrogenic damage. In our laboratory, we are developing nanoparticle- and exosome-mediated systems to deliver engineered protein constructs, or other molecular agents, into mammalian gametes and embryos in experimental scenarios. Such methods could provide a useful tool for studying or manipulating target proteins during fertilization and early embryogenesis, and may, in future, provide an effective means of delivering targeted clinical agents to augment functionality.