Recent developments in the spermatogonial stem cell field

Abstract

This review aims at putting in perspective the many new developments in our understanding of spermatogonial multiplication and stem cell renewal in non-primate mammals.. In the rodent seminiferous epithelium, the spermatogonial compartment can be subdivided into A, In and B spermatogonia, that show no, some or abundant nuclear heterochromatin, respectively. At first, it was thought that all A spermatogonia were spermatogonial stem cells while In and B spermatogonia were in the differentiation pathway. Then there appeared to be a class of so-called undifferentiated A spermatogonia, subdivided according to their topographical arrangement in to singles (As), pairs (Apr) and chains of 4, 8 and 16 Aal spermatogonia. Four (in mouse and rat) subsequent generations of A spermatogonia together with In and B spermatogonia were called differentiating type spermatogonia. A socalled As model was proposed in which the As spermatogonia are the stem cells that self-renew by forming new singles or give rise to Apr spermatogonia that eventually will become spermatozoa. The As model was challenged by the fragmentation model in which stem cell renewal was supposed to occur by way of fragmentation of clones of Aal spermatogonia. However, the fragmentation model has not been supported by convincing evidence. Recently, it was shown that the compartment of As spermatogonia can be subdivided into a class of the most primitive spermatogonial stem cells (SSCu) that are able to form repopulating colonies after transplantation and transient stem cells (SSCt) that are not transplantable but still have some self-renewal capacity. The SSCu can be distinguished by the expression of the marker proteins ID4, PAX7 and BMI1. LIN28a and FXBW7 likely are negative markers. Interestingly, there is some evidence that the SSCu are resistant to the toxic effects of busulfan and irradiation. The most recent scheme of spermatogonial multiplication and stem cell renewal is discussed.