"Human infertility affects ~15% of couples, each partner being equally likely to be affected. Sperm differentiation anomalies such as sperm absence, malformation or reduced motility, are commonly found in infertile men but their cause remains unknown in ~75% of the cases. In mammals, sperm differentiation requires a high proportion of genes located on the sex chromosomes and a tight epigenetic control of their expression. Alterations of the epigenetic marks associated with these spermiogenic genes are expected to contribute significantly to male infertility. The aim of our proposal is to understand the epigenetic regulation of sex chromosomes during sperm differentiation and its impact on male infertility. We will first investigate this process using innovative mouse models; we will then apply knowledge obtained from studies of mice to the study of human physiopathology. The long-term goal is to determine if abnormal epigenetic regulation of spermiogenic genes is at the basis of unexplained cases of human infertility.Through the use of assisted reproductive technologies (ART), the genetic and epigenetic causes of infertility may now be transmitted to subsequent generations, even in cases of severe spermiogenic failure. Between 1 to 4% of children born in the EU are conceived with the help of ART, and recent studies suggest that alterations in the epigenetic program of the father’s germ cells (in case of spermiogenic defects or exposure to environmental factors such as endocrine disruptors) are responsible for a higher incidence in birth defects. A better knowledge of the epigenetic events occurring during spermatogenesis is therefore of critical importance.This proposal will allow an experienced UK-based postdoctoral fellow to join a French team studying human infertilities. There, she will acquire expertise in epigenetics and human reproductive biology and considerably improve her chances of becoming an independent investigator in the near future."