Gonocyte
Gonocytes relate to both fetal and neonatal germ cells from the point at which they enter the testis primordial until they reach the base membrane at the seminiferous cords and differentiate.
One of the models proposes that the PGCs give rise to a single subset of pluripotent gonocytes that either become SSCs from which progenitors then arise or differentiate into type A spermatogonia directly.
The second phase is spermatogenesis, which is a cycle of regulated mitosis, meiosis and differentiation (via spermiogenesis) leading to the production of mature spermatozoa, also known as sperm cells.
[17][18] In between E7.5 and E12.5, these PGCs migrate towards the genital ridge, where they form the testicular cords, via the cytokine interactions of the CXCR4 and c-Kit membrane receptors and their ligands SDF1 and SCF respectively.
[5] In order to provide the long-term production of sperm, gonocytes undergo proliferation to produce a populate pool of SSCs.
[5][14][6] Once enclosed by Sertoli cells to form the testicular cords, gonocytes undergo a succession of differing fetal and neonatal periods of mitosis, with a phase of quiescence in between.
[4] The mitotic activity that occurs in the neonatal period is necessary for the migration of gonocytes to the basement membrane of the seminiferous cords in order to differentiate into the SSCs.
Retinoic acid (RA), the bioactive metabolite of retinal, is a morphogen shown to modulate fetal gonocyte proliferation.
[23][24] Moreover, RA inhibited differentiation by stopping the fetal gonocytes from entering mitotic arrest while simultaneously triggering apoptosis.
RA, by decreasing the overall fetal gonocyte population via apoptosis, is speculated to allow the elimination of mutated and dysfunctional germ cells.
The production of PDGF-BB and E2 by surrounding Sertoli cells activate their respective receptors on neonatal gonocytes, triggering proliferation via an interactive, crosstalk mechanism.
[26][27] The regulation of LIF is speculated to allow gonocytes to become sensitive to Sertoli cell factors that trigger proliferation, such as PDGF-BB and E2.
[31] Inhibition of PDGF receptors and c-Kit by in vivo treatment of imatinib, an inhibitory drug, interrupted migration, leading to a number of gonocytes centrally located in the seminiferous cords.
[32] The differentiation of gonocytes to SSC only occur once the cells have established close contact with the basement membrane in the seminiferous cords.
[37][5] Gonocytes dissociate from these junctions and migrate so that the basal side of the cell is in close proximity with the basement membrane, where they undergo phenotypic changes and take the appearance of spermatogonia.
[38] The development of CIS is due to fetal germ cells, such as gonocytes, arrested in quiescence and unable to properly differentiate.
[40] Individuals diagnosed with cryptorchidism are often at risk of testicular cancer and infertility due to dysfunction in the development of the neonatal germ cells, in particular, the disruption of the differentiation of gonocytes into adult dark-spermatogonia.
[6] It is proposed that this dysfunction is a product of heat stress caused by the undescended testes remaining in the abdomen and unable to regulate its temperature which is often accomplished by the scrotum.
