Determining the molecular mechanism of sperm:oocyte fusion during mammalian fertilization

01 July 2020 → 14 February 2021
Research Foundation - Flanders (FWO)
Research disciplines
  • Natural sciences
    • Proteins
    • General biology not elsewhere classified
    • Cell growth and development
    • Cellular interactions and extracellular matrix
    • Molecular and cell biology not elsewhere classified
proteomic screen Reproductive biology Fertilization
Project description

Fertilization is an important process for species survival. In mammals, fertilization requires the recognition and fusion of the sperm and oocyte to produce a new organism. Recent discoveries have identified the recognition of sperm expressed Izumo to its receptor Juno on the egg to be crucial for fertilization. However, this binding alone is insufficient for fusion, indicating other factors are involved. The host lab has conducted pioneering work in the field of apoptotic cell clearance. Normally, the phospholipid phosphatidylserine (PtdSer) is exposed on apoptotic cells, and functions as a recognition signal for phagocytosis. Interestingly, the host lab noted viable sperm expose PtdSer on their outer membrane, further identified that PtdSer interactions with its cognate receptors on the oocyte are important for fertilization. We hypothesise that PtdSer exposure on sperm is essential for both recognition and fusion of sperm and oocytes. Here, I propose to genetically target mice to produce PtdSer null sperm and define if PtdSer is crucial for fertilization. Furthermore, I will characterize sperm derived vesicles for PtdSer exposure and function in fertilization. Additionally, I will conduct a proximity-based screen to determine novel interacting factors at the sperm:egg fusion surface, and signalling within the oocyte. We anticipate, this study will provide important insights into mammalian fertilization that will have implications for reproductive health and fertility.