Project description
Unravelling fertilisation in mammals
The sperm-specific protein Izumo binds to Juno – its egg receptor counterpart. This binding is essential for fertilisation, but more players must be involved in the process. The EU-funded Sperm-Egg Phusion project will investigate the theory that lipids called phosphatidylserine (PtdSer) on viable sperm and corresponding PtdSer receptors on oocytes (immature egg cells) are instrumental in the fertilisation of mammals. This testing will be performed at molecular, biochemical, cellular, functional and genetic levels. It will explore how PtdSer alters during sperm maturation and what molecular processes control PtdSer’s exposure on viable sperm. In addition, the project will study the genetic importance of various PtdSer receptors in fertilisation and how PtdSer causes novel signals within oocytes.
Objective
Fertilization is essential for a species to survive. Mammalian sexual reproduction requires the fusion between the haploid gametes sperm and egg to create a new diploid organism. Although fertilization has been studied for decades, and despite the remarkable recent discoveries of Izumo (on sperm) and Juno (on oocytes) as a critical ligand:receptor pair, due to the structure of Izumo and Juno, it is clear that other players on both the sperm and the oocytes must be involved. While the focus of our laboratory over the years has been in understanding apoptotic cell clearance by phagocytes, we accidentally noted that viable, motile, and fertilization-competent sperm exposes phosphatidylserine (PtdSer). PtdSer is a phospholipid normally exposed during apoptosis and functions as an ‘eat-me’ signal for phagocytosis. Further, masking this PtdSer on sperm inhibits fertilization in vitro. Based on additional exciting preliminary data, in this ERC proposal, we will test the hypothesis that PtdSer on viable sperm and the complementary PtdSer receptors on oocytes are key players in mammalian fertilization. We will test this at a molecular, biochemical, cellular, functional, and genetic level. From the sperm perspective — we will ask how does PtdSer changes during sperm maturation, and what molecular mechanisms regulate the exposure of PtdSer on viable sperm. From the oocyte perspective — we will test the genetic relevance of different PtdSer receptors in fertilization. From the PtdSer perspective — we will test PtdSer induces novel signals within oocytes. By combining the tools and knowledge from field of phagocytosis with tools from spermatogenesis/fertilization, this proposal integrates fields that normally do not intersect. In summary, we believe that these studies are innovative, timely, and will identify new players involved in mammalian fertilization. We expect the results of these studies to have high relevance to both male and female reproductive health and fertility.
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Funding Scheme
ERC-ADG - Advanced GrantHost institution
9052 ZWIJNAARDE - GENT
Belgium