Male germline stem cells in non-human primates

Abstract

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.

Molecular histology of spermatogenesis in the Japanese macaque monkey (Macaca fuscata)

“…In contrast, protein expression-based molecular dissection has enabled us to characterize the developmental properties of spermatogenesis with precision and detail. Our results indicate that the molecular ontogeny of the Japanese macaque spermatogenesis is essentially similar to that of the rhesus macaque (Fayomi and Orwig 2018;Sharma et al 2017) and the common marmoset (Lin et al 2015(Lin et al , 2012, suggesting an evolutionarily conserved molecular foundation for primate (haplorhine) spermatogenesis. Immunohistological kinetics thus provide a useful new platform for investigating spermatogenesis in the Japanese macaque, which is a prerequisite for investigating their postnatal development and seasonal reproduction.…”

Germline stem cells in human

“…Knowledge about how PGCs are induced comes largely from studies in model mammals, including nonhuman primates, 86 , 87 , 89 – 95 mice, 12 , 83 , 85 , 96 – 108 and pigs. 109 – 118 Studies in the other group of model organisms, including chicken, 119 – 126 zebrafish, 63 , 64 , 66 , 67 , 127 medaka, 128 – 136 frogs, 55 – 57 , 137 Drosophila, 138 – 146 and Caenorhabditis elegans, 147 – 156 provide abundant information about PGC specification by preformation or maternally inherited determinants.…”

“… 159 In recent years, studies in nonhuman primates provide some information for hPGC specification. 87 , 89 , 91 , 95 , 160 …”

“…Specification genes of hPGCs. Knowledge about how PGCs are induced comes largely from studies in model mammals, including nonhuman primates, 86,87,[89][90][91][92][93][94][95] mice, 12,83,85,[96][97][98][99][100][101][102][103][104][105][106][107][108] and pigs. [109][110][111][112][113][114][115][116][117][118] Studies in the other group of model organisms, including chicken, [119][120][121][122][123][124][125][126] zebrafish, 63,64,66,67,127 medaka, [128][12...…”

“…159 In recent years, studies in nonhuman primates provide some information for hPGC specification. 87,89,91,95,160 In PGCs of humans and nonhuman primates, a core group of primate-specific PGC markers is expressed, including SOX17, BLIMP1, TFAP2C, NANOG, and POU5F1, but the absence of SOX2, 87,90,95,160,161 suggesting that these factors are conserved and are important for PGC specification in primates. Nevertheless, it is perhaps different from the origin of hPGCs, that PGCs in cynomolgus monkey might emerge in amnion.…”