Male germline stem cells in non-human primates

Abstract

Over the past few decades, several studies have attempted to decipher the biology of mammalian germline stem cells (GSCs). These studies provide evidence that regulatory mechanisms for germ cell specification and migration are evolutionarily conserved across species. The characteristics and functions of primate GSCs are highly distinct from rodent species; therefore the findings from rodent models cannot be extrapolated to primates. Due to limited availability of human embryonic and testicular samples for research purposes, two non-human primate models (marmoset and macaque monkeys) are extensively employed to understand human germline development and differentiation. This review provides a broader introduction to the in vivo and in vitro germline stem cell terminology from primordial to differentiating germ cells. Primordial germ cells (PGCs) are the most immature germ cells colonizing the gonad prior to sex differentiation into testes or ovaries. PGC specification and migratory patterns among different primate species are compared in the review. It also reports the distinctions and similarities in expression patterns of pluripotency markers (OCT4A, NANOG, SALL4 and LIN28) during embryonic developmental stages, among marmosets, macaques and humans. This review presents a comparative summary with immunohistochemical and molecular evidence of germ cell marker expression patterns during postnatal developmental stages, among humans and non-human primates. Furthermore, it reports findings from the recent literature investigating the plasticity behavior of germ cells and stem cells in other organs of humans and monkeys. The use of non-human primate models would enable bridging the knowledge gap in primate GSC research and understanding the mechanisms involved in germline development. Reported similarities in regulatory mechanisms and germ cell expression profile in primates demonstrate the preclinical significance of monkey models for development of human fertility preservation strategies.

Figure 1

Schematic representation of comparative expression profiles of prenatal, perinatal and adult germ cell markers in marmoset and rhesus monkeys. Prenatally expressed markers constitute primordial germ cells (PGCs), the embryonic precursors of male gametes, and gonocytes (Gono), cells located in seminiferous tubules. Prespermatogonia are the cells migrating to the basal lamina, whereas spermatogonia (Spg) are already in direct contact with basal lamina. A sub-population of these spermatogonial stem cells further mature into more differentiated cells including B spermatogonia (B), spermatocytes (Spc), round (RS) and elongated spermatids, and finally into spermatozoa. Expression patterns of various germ cell markers across different developmental stages are represented by colored bars (1: Aeckerle et al., 2015; 2: Mitchell et al., 2008; 3: McKinnell et al., 2013; 4: Albert et al., 2010; 5: Eildermann et al., 2012a; 6: Lin et al., 2015; 7: Aeckerle et al., 2015; 8: Westernströer et al., 2015; 9: Lin et al., 2012; 10: Eildermann et al., 2012b; 11: Sasaki et al., 2016; 12: Hermann et al., 2007; 13: Hermann et al., 2009).