Undifferentiated primate spermatogonia and their endocrine control

Abstract

The biology of spermatogonial stem cells is currently an area of intensive research and contemporary studies in primates are emerging. Quantitative regulation of sperm output by the primate testis seems to be exerted primarily on the transition from undifferentiated to differentiating spermatogonia. This review examines recent advances in our understanding of the mechanisms governing spermatogonial renewal and early differentiation in male primates, with a focus on the monkey. Emerging revisions to the classic view of dark and pale type A spermatogonia as reserve and renewing spermatogonial stem cells, respectively, are critically evaluated and essential features of endocrine control of undifferentiated spermatogonia throughout postnatal primate development are discussed. Obstacles in gaining a more complete understanding of primate spermatogonia are also identified.

Figure 1

Schematic of the seminiferous epithelial cycle of the (a) rodent (rat) and (b)primate (rhesus monkey). The initiator of the rodent seminiferous epithelium cycle is provided by the synchronized and repetitive transformation (hashed arrow) of Aal to A1 spermatogonia, whereas, in the monkey, this function is provided by the synchronized and repetitive mitosis (arrowhead) of Ap to produce B1. The rat epithelial cycle repeats every 13 days, whereas the cycle of the monkey has a period of 10.5 days. Roman numerals indicate stages of the seminiferous epithelial cycle. In, intermediate spermatogonia; PL, preleptotene spermatocyte.

Figure 2

Correlation of changes in the number of type A pale spermatogonia (total type A pale [Ap, red line], small Ap [Aps, green line], and large Ap [Apl, orange line]) with those of type B1 (B1, blue line) spermatogonia (a) in relationship to the mitotic labeling index of total type A pale (b) during the 12 stages of the seminiferous epithelium cycle of the rhesus monkey. Note the broad peak in labeling of Ap during Stages VII to XI and the temporal association between the disappearance of Ap and appearance of B1. Redrawn from ref [17].

Figure 3

Molecular phenotypes of monkey spermatogonia. (a) Correlation of nuclear staining patterns (PAS-hematoxylin) of Ad (A_dark), Ap (A_pale) and B4 spermatogonia in testis of adult rhesus monkeys with immunostaining for molecular markers (GFRα1 [i-iv], PLZF [v-viii], NGN3 [ix-xiii] and cKIT [xiv-xviii]) of rodent spermatogonia. The left hand column of photomicrographs (lower power images) shows arcs of seminiferous tubule (scale bar, 50 µm). High power images of selected spermatogonia are shown to the right (scale bar, 10 µm). (b) The table presents the percentage (mean±SEM) of A_dark and A_pale labeled with each of the 4 markers. Reprinted from ref .

Figure 4

A model for the action of FSH to amplify spermatogenic output in the monkey. Circulating FSH concentrations govern the fraction of A pale spermatogonia in the cycling pool. As levels of this gonadotropin increase, the pool of cycling Ap is expanded resulting in an increased number of B1 spermatogonia that are produced in stage X of the seminiferous epithelial cycle as a result of the differentiating division of Ap at this time. The total number of A pale spermatogonia is not FSH dependent. Under normal conditions, the monkey testis is not operating at its spermatogenic ceiling and sperm output is regulated by the blood level of FSH [1].