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.