title: Male germ cell gene expression.
abstract: Formation of the male gamete occurs in sequential mitotic, meiotic, and postmeiotic phases. Many germ cell-specific transcripts are produced during this process. Their expression is developmentally regulated and stage specific. Some of these transcripts are product of genes that are male germ cell-specific homologs of genes expressed in somatic cells, while some are expressed from unique genes unlike any others in the genome. Others are alternate transcripts derived from the same gene as transcripts in somatic cells but differing from them in size and/or overall sequence. They are generated during gene expression by using promoters and transcription factors that activate transcription at different start sites upstream or downstream of the usual site, by incorporation of alternate exons, by germ cell-specific splicing events, and by using alternate initiation sites for polyadenylation. Male germ cell development consists of an assortment of unique processes, including meiosis, genetic recombination, haploid gene expression, formation of the acrosome and flagellum, and remodeling and condensation of the chromatin. These processes are intricate, highly ordered, and require novel gene products and a precise and well-coordinated program of gene expression to occur. The regulation of gene expression in male germ cells occurs at three levels: intrinsic, interactive, and extrinsic. A highly conserved genetic program "intrinsic" to germ cells determines the sequence of events that underlies germ cell development. This has been underscored by recent studies showing that meiosis involves many genes that have been conserved during evolution from yeast to man. During meiosis and other processes unique to germ cells, the intrinsic program determines which genes are utilized and when they are expressed. In the postmeiotic phase, it coordinates the expression of genes whose products are responsible for constructing the sperm. The process of spermatogenesis occurs in overlapping waves, with cohorts of germ cells developing in synchrony. The intrinsic program operating within a particular germ cell requires information from and provides information to neighboring cells to achieve this coordination. Sertoli cells are crucial for this "interactive" process as well as for providing essential support for germ cell proliferation and progression through the phases of development. The interactive level of regulation is dependent on "extrinsic" influences, primarily testosterone and follicle-stimulating hormone (FSH). Studies during the last 4 years have established that FSH is not essential for germ cell development but instead serves an important supportive role for this process. While testosterone is essential for maintenance of spermatogenesis, it acts on Sertoli cells and peritubular cells and has indirect effects on germ cells. The extrinsic and interactive processes are extremely important for establishing and maintaining an optimum environment within which gametogenesis occurs. Nevertheless, an intrinsic evolutionarily conserved genetic program regulates male germ cell gene expression and development.
authors.affiliation: Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709-2233, USA. eddy@niehs.nih.gov
authors.forename: Edward M
authors.initials: EM
authors.lastname: Eddy
mesh_terms: D000818:Animals; D017209:Apoptosis; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008540:Meiosis; D008938:Mitosis; D012708:Sertoli Cells / Q000502:physiology; D013091:Spermatogenesis / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism*