Dr. Junaid Kashir’s Research Project Supported by Khalifa University’s Faculty Start-up Grant, Offers Scope for Infertility Challenges
A team of researchers led by a Khalifa University faculty has identified for the first time the essential role of a sperm protein in ensuring high embryo quality and successful pregnancy rates in humans. The study on the protein called phospholipase C zeta (PLCζ), responsible for ensuring successful fertilization in mammals, during the early stages of embryogenesis, has important implications for addressing infertility challenges.
The research was published in the paper titled ’ in the Oxford Academic journal Human Reproduction. The research team, led by Dr. Junaid Kashir, Associate Professor, Biological Sciences, Khalifa University College of Medicine and Health Sciences, (CMHS). The project was also supported by Khalifa University’s faculty start-up grant.
The researchers discovered that levels of this specific sperm protein are closely linked to the success of early embryonic development and successful pregnancy outcomes, where an optimal range of this protein was required to cause successful embryogenesis and pregnancy. Couples where the male partner’s sperm had PLCζ levels above a certain threshold were significantly more likely to achieve a successful pregnancy through fertility treatment, compared to those with lower PLCζ levels.
Key institutions that were part of the research project included King Faisal Specialist Hospital and Research Centre (KFSH&RC), Saudi Arabia, and the College of Medicine, QU Health, Qatar University,
Dr. Kashir said: “Our data suggests this important sperm protein could be a valuable biomarker to help guide fertility treatments and for the first time the clinical utilization of PLCζ may stand to benefit not just a specific population of male infertility but a larger population of couples seeking fertility treatment. Male patients whose sperm had levels of this protein below a threshold while leading to successful fertilization, led to poorer embryogenesis and resulted in lower pregnancy success rates. However, patients whose sperm had levels of this protein higher than this threshold led to good quality of embryogenesis and almost double the pregnancy success. This represents the first time that PLCf levels in sperm have been correlated to predictive measures of embryogenic efficacy and pregnancy rates in humans. ”
A total of 54 couples were analyzed at the KFSH&RC for this study. Patient samples and data for this study were obtained from consecutive treatment cycles of couples undergoing fertility treatment in the ART laboratory at the King Faisal Hospital and Research Centre (KFSH&RC), Riyadh, Saudi Arabia.
To further support this data, the research team generated the first genetically engineered mice via CRISPR-Cas9 gene-editing technology in Saudi Arabia at the KFSH&RC, in order to gain a broader understanding of the function of the gene responsible for producing the PLCζ protein in the body. This precise gene modification allowed the team to observe that mice lacking the PLCζ protein exhibited an increase in the rate of polyspermy, leading to early embryo development failure and consequently fewer births compared to mice with normal protein levels.
Researchers emphasize that the test should be expanded to examine a multicenter group since the variables for infertility rates differ from one human group to another and that the results from the mutant mouse suggest the significant role of PLCζ in early embryo development.
All procedures and experiments involving laboratory animals were approved by the Institutional Animal Care and Use Committees (IACUC) and Research Advisory Council (RAC) at the KFSH&RC. The mice were raised and maintained in the Association for Assessment and Accreditation of Laboratory Animal Care International accredited laboratory animal facility. The experimental procedures involving mice were carried out according to the Animal Research: Reporting of In Vivo Experiments (ARRIVE) and IACUC guidelines. Human patient recruitment was approved by the local research ethics committee and the office of research affairs at the KFSH&RC.
Clarence Michael
English Editor – Specialist
22 Aug 2024
