Spermatogenesis

Abstract

Production of male gametes, i.e., spermatogenesis, takes place in the seminiferous tubules of the testis. It is a multifaceted, process that takes 2.5 months to complete in man and results in formation of the most highly specialized cell type in the human body, the sperm. The seminiferous epithelium is in constant turnover as new generations of germ cells start to differentiate on the basal lamina and mature gametes are released from the apical part to the tubular lumen. Different generations of germ cells ensue spermatogenesis in synchrony and therefore over a period of time, called the cycle, the seminiferous epithelium has the same appearance. Ability to produce sperm spans the lifetime of sexually mature males and ultimately depends on germ-line stem cell (GSC) self-renewal. GSCs are maintained in a niche created by somatic cells and tissue microenvironment. Transmission of genetic information to subsequent generations and perpetuation of the species ultimately depend on GSC maintenance and the delicate balance between GSC self-renewal and differentiation. Spermatogenesis needs to be kept at a quantitatively normal level to sustain male fertility. Sertoli cells are the somatic component of the seminiferous epithelium, and they create the microenvironment that enables germ cells to survive, proliferate, and differentiate. Sertoli cells show unparalleled plasticity in gene expression and function during development and across the cycle of the seminiferous epithelium, and germ cells are dependent on management of their differentiation by Sertoli cells. Sertoli cells are targets of pituitary-derived follicle-stimulating hormone (FSH) and testosterone, produced in Leydig cells of testicular interstitium under control of luteinizing hormone (LH), and they transduce these signals and other stimuli into paracrine regulation of spermatogenesis and coordinate gene expression in germ cells. The transcriptome of male germ cells presents one of the widest among all cell types including not only thousands of protein-coding RNAs but also a wide range of short noncoding RNAs that play a pivotal role in posttranscriptional control of gene expression. Many hormones and factors control spermatogenesis and GSC maintenance, but testosterone, retinoic acid (RA), and FSH action are needed to optimize sperm production. FSH mainly affects premeiotic germ cells, whereas testosterone and RA act throughout male germ cell differentiation. However, quantitatively and qualitatively normal spermatogenesis requires all of them.