Gene regulation in spermatogenesis

Abstract

Mammalian spermatogenesis is a complex hormone-dependent developmental program in which a myriad of events must take place to ensure that germ cells reach their proper stage of development at the proper time. Many of these events are controlled by cell type- and stage-specific transcription factors. The regulatory mechanisms involved provide an intriguing paradigm for the field of developmental biology and may lead to the development of new contraceptives an and innovative routs to treat male infertility. In this review, we address three aspects of the genetic regulatory mechanism that drive spermatogenesis. First, we detail what is known about how steroid hormones (both androgens and estrogens) and their cognate receptors initiate and maintain mammalian spermatogenesis. Steroids act through three mechanistic routes: (i) direct activation of genes through hormone-dependent promoter elements, (ii) secondary transcriptional responses through activation of hormone-dependent transcription factors, and (iii) rapid, transcription-independent (nonclassical) events induced by steroid hormones. Second, we provide a survey of transcription factors that function in mammalian spermatogenesis, including homeobox, zinc-finger, heat-shock, and cAMP-response family members. Our survey is not intended to cover all examples but to give a flavor for the gamut of biological roles conferred by transcription factors in the testis, particularly those defined in knockout mice. Third, we address how testis-specific transcription is achieved. In particular, we cover the evidence for and against the idea that some testis-specific genes are transcriptionally silent in somatic tissues as a result of DNA methylation.