Spermatogenesis
Normal fertility in the male requires the constant production of large numbers of gametes over a long time period. Spermatogenesis is a very complex, highly organized and regulated process that involves mitosis, meiosis and unique pathways of differentiation. In general, spermatogenesis involves three major biological fundamentals: (a) the renewal of stem cells and the production and expansion of progenitor cells (mitosis) (b) the reduction, by one-half, of the chromosome numbers in progenitor cells (meiosis) and (c) the unique differentiation of haploid cells (spermiogenesis). Early progenitor cells or spermatogonia are defined as “undifferentiated” or A spermatogonia in the mouse. Once the spermatogonia enter the “differentiation” pathway they begin the series of differentiation steps leading to meiosis and spermiogenesis. The endocrine regulation of spermatogenesis occurs by the interplay of gonadotropins and steroids with the somatic cells of the seminiferous tubules (Sertoli cell and Leydig cells) and of vitamin A directly with the germinal cells.
The research in my laboratory has been directed towards the understanding of mammalian spermatogenesis at the molecular level. Our current studies are focused on the role of vitamin A in this process. In particular we are interested in the mechanisms by which retinoic acid (vitamin A) influences the commitment of germ cells to enter meiosis. These mechanisms are central to the timing of sperm production and the organization of gametogenesis.
In our initial approach we developed extensive mRNA and microRNA expression data bases for both germ cells and somatic cells in the testis using array technology and we are currently enhancing that information using next generation sequencing. Our databases cover nearly all aspects of spermatogenesis including cell specific expression and hormone responsive transcription and are used by investigators worldwide. Our latest emphasis has been on discovering the genes expressed in germ cells that enable the entry of these cells into meiosis. We then examine the role of these genes using a variety of genetic approaches with transgenic mice. The projects span the disciplines from biochemistry to genetics to cell biology.