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QU Researchers Unravel the Complex Sperm Factors that Trigger Egg Development into an Embryo upon Fertilization | Qatar University

QU Researchers Unravel the Complex Sperm Factors that Trigger Egg Development into an Embryo upon Fertilization

2018-01-31 00:00:00.0

Doha, Qatar, 31 January 2018: A ground-breaking research project by Qatar University (QU) research team and external collaborators assessed the veracity of PAWP (post acrosomal WW domain-binding protein) versus PLC-zeta (PLCz), as the major sperm-derived protein candidates for initiating Ca2+ oscillations in the unfertilized egg. Understanding this vital Ca2+ signalling mechanism will contribute to major therapeutic developments in the field of assisted reproductive technology.

Led by QU College of Medicine (CMED) Assistant Professor of Biochemistry Dr Michail Nomikos, the team includes recently-recruited CMED Professor of Molecular and Cellular Biology Prof Anthony Lai and research collaborator Prof Karl Swann (Cardiff University, UK).

They completed a research project titled “Is PAWP the "real" sperm factor?”. Their research paper won the “Outstanding Paper Award 2017”, an accolade given by the Asian Journal of Andrology (AJA) for the most influential publications that provide significant impact in reproductive medicine.

At fertilization, the primary event following fusion of the sperm and egg (oocyte) is a series of transient rises in the intracellular free Ca2+ concentration, termed Ca2+ oscillations. Over the past decade, mounting experimental and clinical evidence has been congruent with the hypothesis that the sperm factor responsible for the initiation of Ca2+ oscillations during mammalian fertilization is a testis-specific isoform of PLC-zeta (PLCz). The prize-winning study compared PLCz with PAWP, a sperm head protein that exclusively resides in the postacrosomal sheath region of the perinuclear theca. In a FASEB Journal paper, it was claimed that PAWP produces Ca2+ oscillations and pronuclear formation in human and mouse oocytes similar to that observed during intracytoplasmic sperm injection. This competing claim made for PAWP highlights the requirement to determine the relative contributions of PAWP and PLCz in enabling successful fertilization to occur.

To date, no research groups have independently verified PAWP’s ability to activate oocytes and/or cause Ca2+ oscillations, Dr Michail Nomikos said. He added: “We investigated whether PAWP can initiate Ca2+ oscillations and oocyte activation in the mouse. We microinjected into mouse oocytes the recombinant mouse PAWP protein but we consistently failed to observe any Ca2+ increases. Additionally, PAWP was unable to hydrolyse PIP2 in vitro and also did not act as a generic activator of PLCz activity.”

Prof Lai noted that the research culminating in this prize-winning paper have provided an immense development in the field of fertilization and assisted reproduction technology by revealing major technical issues in the debate regarding the identity of the “sperm factor” – these advances point to PLCz as a critical protein responsible for initiating the physiological process of human fertilization. Prof Lai’s team was the first in the world to identify PLCz as the “sperm factor” (“spark of life”; The Times, UK) that initiates egg activation and embryo development at fertilization, a phenomenon that has been verified by numerous laboratories worldwide.

Commenting on this research, QU Vice President for Medical and Health Sciences and CMED Dean Dr Egon Toft said: “This award-winning research is an excellent example of the important biomedical projects taking place at CMED and demonstrates the highest level of competency and excellence in research. International recognition of this research success positively reflects the College’s collaborative efforts with local and international institutions to advance the health care sector in Qatar and beyond, and will further promote biomedical research on health care issues of great interest and benefit to society. Importantly, it also demonstrates QU’s firm commitment to offering high-quality research to serve the community in line with Qatar National Health Strategy.”