Médecine de la Reproduction


Proteomics, a powerful technology to help understanding normal and pathological spermatogenesis Volume 14, issue 4, Octobre-Novembre-Décembre 2012


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Inserm, U1085, Irset, université de Rennes I, campus de Beaulieu, 35042 Rennes, France

Spermatogenesis is a highly sophisticated process involved in transmission of genetic heritage. It includes halving ploidy, repackaging of the chromatin for transport, and equipment of developing spermatids and eventually spermatozoa with the advanced apparatus (e.g. tightly packed mitochondrial sheat in the mid piece, elongating of the tail, reduction of cytoplasmic volume) to elicit motility once they reach the epididymis. Mammalian spermatogenesis is classically divided into three phases. In the first — the proliferative or mitotic phase — primitive germ cells or spermatogonia undergo a series of mitotic divisions. In the second — the meiotic phase — the spermatocytes undergo two consecutive divisions to produce haploid spermatids. In the third — spermiogenesis — spermatids differentiate into spermatozoa. Paracrine, autocrine, juxtacrine and endocrine pathways all contribute to regulation of the process; the array of structural elements and chemical factors modulating somatic and germ cell activity is such that the network linking the various cellular activities during spermatogenesis is unimaginably complex. Over the past two decades, advances in genomics have greatly improved our knowledge of spermatogenesis, by identifying numerous genes essential for the development of functional male gametes. Large-scale analyses of testicular function have deepened our insight into normal and pathological spermatogenesis. Progresses in genome sequencing and microarray technology have been exploited for genome-wide expression studies, leading to the identification of hundreds of genes differentially expressed within the testis. However, although proteomics has now come of age, the proteomics-based investigation of spermatogenesis remains in its infancy. Here, we review the state-of-the-art of large-scale proteomic analyses of spermatogenesis, from germ cell development during sex determination to spermatogenesis in the adult. Indeed, a few laboratories have undertaken differential protein profiling expression studies and/or systematic analyses of testicular proteomes in entire organs or isolated cells from various species. We consider the pros and cons of proteomics for studying the testicular germ cell gene expression program. Finally, we address the use of protein datasets, through integrative genomics ( i.e., combining genomics, transcriptomics and proteomics), bioinformatics and modelling.