How PLCzeta Research Can Revolutionise Male Infertility
A WRH Research Group operates within our department's Reproduction and Genetic theme, lead by Prof. Kevin Coward
Sperm, oocyte activation deficiency, and phospholipase C zeta
Why this project is important?
PLCzeta is a sperm-specific protein responsible for activating the oocyte at fertilisation and therefore plays a critical role in creating a viable embryo. We have a long history of investigating how PLCzeta, and other proteins in either the sperm or oocyte, might be related to certain types of male factor infertility, including oocyte activation deficiency, total fertilisation failure, and recurrent intracytoplasmic sperm injection (ICSI) failure. Our work aims to develop new diagnostic and therapeutic tools to facilitate the management and treatment of patients experiencing these problems.
How WE can help
Our research has already led to the development of a PLCzeta assay that can detect PLCzeta deficiency in semen samples from patients. Our research assay is available at The Fertility Partnership Oxford under appropriate ethical legislation and recruitment criteria.
The assay can identify PLCzeta-deficiency in human sperm samples, thus providing specific evidence for the clinical use of artificial oocyte activating agents (AOAs), which at present, represent the only option for treatment. We are also synthesising a recombinant form of PLCzeta that could represent a far more efficient and endogenous alternative to AOAs.
WHAT WE ARE DOING
Activation of the oocyte at fertilisation 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 directly responsible for this is PLCzeta, a specific phospholipase C with distinctive properties.
We investigate how PLCzeta, 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 PLCzeta, and other sperm proteins, in order to induce activation.
At present, the only treatment available for couples with PLCzeta-related infertility are artificial oocyte activating agents (AOAs), which are only available in some fertility clinics.
The clinical use of these agents creates an environment in which an oocyte is ‘chemically tricked’ into activating. Our work aims to control the use of AOAs by providing scientific evidence for a need to improve oocyte activation capability and by identifying patients who are most likely to benefit from AOAs in their next treatment cycle.
20% of all infertile cases remain unexplained and could be attributed to an as yet undetermined deficiency in the molecular identity or function of sperm. - Kevin Coward
WHAT WE HOPE TO ACHIEVE
PLCzeta activates (wakes up) the egg at fertilisation and initiates the formation of an embryo.
In some males, PLCzeta does not work properly; this can result in infertility. This cause of infertility cannot be detected by routine clinical tests. Our research aims to enhance our knowledge of this condition so that we can diagnose and treat PLCzeta-related infertility.
UPDATE: How our research is going?
We have already developed a research-based assay that can detect PLCzeta deficiency in semen samples from patients attending The Fertility Partnership Oxford under appropriate ethical legislation and recruitment criteria. Thus far, we have screened over 300 patients, allowing us to provide scientific advice to the clinicians to consider when developing treatment strategies.
Our clinical assay has given us a far greater understanding of the role of PLCzeta in human infertility how me might use this knowledge for diagnostic and therapeutic purposes. We have developed a recombinant form of PLCzeta that is undergoing a series of tests, and published several papers related to our clinical assay and what we have learnt from this assay with regards to diagnostic tests and therapeutic strategies.
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Useful links
Reproduction and Genetics
Nuffield Department of Women's and Reproductive Health manages over 30 research groups that fall within either Global Health, Cancer, Maternal & Fetal Health; Big data; and Reproductive Medicine & Genetics.
Molecular delivery systems for gametes and embryos.
A WRH Research Group operates within our department’s Reproduction and Genetics theme and is run by Prof. Kevin Coward
MSC in Clinical Embryology
Oxford Universities one-year, residential-taught Masters course aims to provide graduates from either a scientific or clinical background with advanced theoretical and practical understanding of human reproductive biology, embryology, infertility and assisted reproductive technology (ART).
Latest publications
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Sperm chromatin: Evaluation, epigenetic signatures and relevance for embryo development and assisted reproductive technology outcomes
Journal article
Balder P. et al, (2024), European Journal of Cell Biology, 103, 151429 - 151429
The research team
How can you help?
You can support the ongoing work of the PRAMH project through donations, collaborations and research support. If you wish to support our work, please contact us or email Kevin Coward using the button below.