Genetic analysis of the somatic cell niche and male germline stem cell development

Abstract

Male germline stem cells colonize testis tubules and are positioned on the basement membrane. These either self‐renew or commit to spermatogonial progenitors which undergo mitotic and meiotic divisions and finally produce spermatozoa. The stem cells are surrounded by somatic Sertoli cells that from a microenvironment or niche. The interstitial Leydig cells also influence male germ cell development. Sertoli and Leydig cells are sensitive to gonadotropins, FSH (acts on Sertoli cells) and LH (acts on Leydig cells) that are heterodimers (a common α, and hormone‐specific β). We have generated mice lacking either FSHβ or LHβ, and hence FSH or LH. FSHβ null mice are hypogonadal, have reduced number of germline stem cell progenitors, qualitatively normal, but quantitatively reduced spermatogenesis and normal fertility. Genetic removal of cyclin D2, a cell cycle regulator, over the FSHβ null background caused more severe hypogonadism, aberrant Sertoli cell maturation and defects in spermatogenesis and complete infertility. LHβ null mice are hypogonadal, have low testosterone, defective steroidogenesis and are infertile. Defects in Leydig cells, Sertoli cells, Sertoli‐germ cell junctions and a block in spermatogenesis are observed. Thus, these mouse models allow us to developmentally track the properties of somatic cell niche, and how it influences male germline stem cell self‐renewal and differentiation.