EPAS1 Is Required for Spermatogenesis in the Postnatal Mouse Testis

EPAS1 Is Required for Spermatogenesis in the Postnatal Mouse TestisMammalian spermatogenesis is a complex process involving precisely regulated stem cells, coordinated hormone and growth factor signaling, and a maturation and release process that ensures sperm production throughout masculine life. Germ cells are specified and separated from somatic cells during early embryogenesis. As the embryonic testes are formed, Sertoli cells sequester gonocytes inside the newly formed seminiferous tubules (testicular cords), preventing them from entering meiosis. After birth, Sertoli cells and germ cells undergo rapid proliferation. Tight junctions are formed between Sertoli cells from 7 to 14 days postpartum (dpp) to create the blood-testis barrier (BTB), and germ cells enter meiosis and differentiate into spermatozoa. The Sertoli cells, which are directly attached to the basement membrane, are also connected to the spermatogonia and provide nutrients and regulatory factors. Tight junction complexes are formed between adjacent Sertoli cells, thereby creating an outer (basal) and inner or adluminal compartment. Disruption of these junctions results in defects in spermatogenesis. Serum macromolecules are effectively excluded from the adluminal section, which is an essential prerequisite for spermatogenesis, creating a microenvironment consisting exclusively of Sertoli cell secretions and germ cells.read
Also attached to the basement membrane are the most undifferentiated germ cells, the type A spermatogonia (see Figs. 4A and 9C). Spermatogonial stem cells (SSCs), like other stem cells in the organism, are characterized by their ability to self-renew and maintain an appropriate number of undifferentiated cells. As these cells differentiate, they migrate away from the lamina and toward the tubular lumen, where they are released upon maturation into spermatozoa. The systematic maintenance of spermatogenesis is controlled by a number of factors, including hormones, temperature, and O2 availability. Evidence shows that the testis is hypoxic and that the spatially well-orchestrated process of spermatogenesis occurs along a profound O2 partial pressure gradient. The ability to control O2 homeostasis is essential for multicellular organisms. The cardiovascular, hematopoietic, and respiratory organs provide proper oxygenation to all cells and tissues. Whereas ambient air contains 21% O2, most tissues maintain O2 tensions between 2% and 9%. Of note, the testis has been reported to be a naturally O2-deprived organ. Decreased O2, or ‘‘hypoxia,’’ occurs in a number of processes (e.g., embryonic development, postnatal organogenesis, and disease). The heterodimeric hypoxia-inducible factors (HIFs) are critical transcriptional regulators of systemic and cellular responses to hypoxia.

This entry was posted in Spermatogenesis and tagged developmental biology, hypoxia, Sertoli cells, signal transduction, Sperm, spermatogenesis, testis, tight junctions.