Infertility Caused by Polymorphisms or Mutations in Spermatogenesis‐Specific Genes

Spermiogenesis Germ cells differentiate and function to transmit the parental genome to descendant generations. All of the attributes of germ cells that distinguish them from somatic cell lines are related to this prime function. Germ cells differentiate by either oogenesis or spermatogenesis to form eggs and sperm, respectively. Meiosis occurs exclusively in the formation of eggs and sperm and is indispensable for maintaining the species (Tanaka and Baba, 2005). Another function specific to dividing germ cells is maintenance of chromosome telomere length (Tian et al, 2005). Telomere length changes gradually through successive mitotic somatic cell divisions, and this ultimately results in cell death. In male germ cells, many dramatic morphological changes occur during spermatogenesis, especially in haploid spermatids after meiotic division (Russell et al, 1990). In various mammals, male germ cell differentiation proceeds actively and continuously in the testis after puberty, and sperm are produced throughout adulthood (Russell et al, 1990). One month of male cell differentiation in mice (2 months in humans) is required for completion of spermatogonial stem cell proliferation and differentiation, meiosis, generation of haploid germ cells, and morphogenesis of the developing sperm in somniferous tubules (Russell et al, 1990). After meiotic division (during the process of haploid germ cell differentiation, or spermiogenesis), the rounded spermatids undergo marked morphological changes to become sperm: the nucleus assumes a compact shape, the mitochondria are rearranged, the flagellum forms, and the acrosome is generated. During this period of differentiation, which takes about 5 to 6 weeks in humans (Clermont, 1963; Heller and Clermont, 1963) and 2 to 3 weeks in mice (Oakberg, 1956), haploid germ cells do not divide, but morphogenesis occurs, indicating that some regulatory mechanism arrests the cell cycle. Searching for functional changes in genes and gene products involved in male infertility would increase our understanding of the causes of this problem, and perhaps lead to treatment in some cases. Comprehensive isolation and analysis of haploid germ cell–specific genes showed that a large number of specific molecules are involved in spermiogenesis (Tanaka et al, 1994, 2002b; Fujii et al, 2002). The most straightforward strategy for elucidating the mechanism of spermatogenesis is to identify and characterize differentiation-specific molecules and their associated genes in germ cells.