Unraveling genetic causes and risk factors for severe male infertility

This research will significantly advance our molecular and clinical understanding of human spermatogenesis and severe male infertility. We will study the germline genomes of men with selected infertility syndromes as well as large-cohorts of men with non-obstructive azoospermia, aiming to identify pathogenic mutations in novel male infertility genes and non-coding genomic regions, including complex Y chromosomal abnormalities. In addition, we will use innovative flow cytometry and transcriptomics approaches to study normal and abnormal human spermatogenesis. Finally, we will study the consequences of assisted reproductive technologies for the genome of offspring, and look at the preservation of fertility in this offspring. Throughout this research, we will make use of unique material from infertile patients, their parents and their offspring born through ART. This will allow us study the role of de novo germline as well as somatic mutations as unappreciated causes of severe male infertility. The results of this research will be used to develop novel diagnostic procedures and improve the diagnostic yield in this largely unexplained patient cohort. In addition, this research will provide crucial biological information for the development of novel fertility procedures and provide improved methods to monitor the safety of these procedures.