From Villains to Heroes: Insights into the Antagonizing Functions of Prion like Genes and Proteins

During the past decades, prion proteins, the pathological agents causing sporadic, genetic and infectious neurodegenerative disorders, have constituted major concerns for public health authorities. Although the molecular mechanisms of these diseases are not completely understood, the invariably fatal outcome in humans [namely Kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome, fatal insomnia and new variant CJD (vCJD)] and animals (bovine spongiform encephalopathy and scrapie in sheep) has partly overshadowed the physiological action of prions. In fact, increasing evidence support the essential role of prion and prion-like proteins in reproductive physiology. This review examines the roles played by prion (PrPc), prion-like testis specific (Prt), Shadoo and Doppel genes and proteins, in reproductive physiology, and is supported by the expertise acquired by our group in this domain. This covers spermatogenesis, sperm motility, zona binding, fertilization, 3D NMR structure, as well as the evaluation of the genetic regulation of these genes in granulosa cells, using novel techniques of gene silencing (siRNAs) and epigenetic analysis (methylation). This review will thus appraise key issues concerning the biological characters and physiological functions of prion like family members in reproduction.