A structural approach to understanding the role of the centrioles in human sperm

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An overall decline in fertility across the globe has led to an increase in the use of assisted reproductive technologies (ART). Despite the increased need for ART, the success rates are still low (<25% for women younger than 35 and even lower for older women), thus requiring multiple cycles. ART success rates can be improved with correct diagnosis of the cause of infertility. Male infertility is one of the major reasons for couples to attempt ART. However, more than 60% of male infertility is considered idiopathic, highlighting that there is a need for a more detailed understanding of sperm biology. One of the most frequently used approaches in ART is intracytoplasmic sperm injection (ICSI), in which a single sperm cell is selected and directly injected into an oocyte. The fertilized oocyte can then be transferred into the uterus to develop into an embryo. A crucial step in ICSI is the selection of a single sperm cell for injection. Often the main criteria for this selection is gross morphology but the low success rates in ART call for new tools and criteria to assess sperm quality before ICSI. Sperm centrioles are organelles that are entirely responsible to orchestrate the first cell division, as oocytes do not have centrioles of their own. Thus, when the sperm centrioles or their structure are impaired, this will lead to embryo development defects and pregnancy loss. Compared to somatic cells, sperm centrioles were shown to undergo a significant remodeling process during sperm maturation. The main aim of this project is to provide a detailed view of human sperm centrioles using cryo-electron tomography. Centrioles from mature sperm cells of fertile and infertile patients as well as centrioles in early spermatids (immature sperm cells) will be compared. The project will provide a detailed molecular understanding of fertile human sperm centrioles. In addition, it may allow the identification of molecular and structural details causing infertility in men and consequently improve sperm selection for ICSI.