Molecular signatures to define spermatogenic cells in common marmoset (Callithrix jacchus)

Abstract

Germ cell development is a fundamental process required to produce offspring. The developmental program of spermatogenesis has been assumed to be similar among mammals. However, recent studies have revealed differences in the molecular properties of primate germ cells compared with the well-characterized mouse germ cells. This may prevent simple application of rodent insights into higher primates. Therefore, thorough investigation of primate germ cells is necessary, as this may lead to the development of more appropriate animal models. The aim of this study is to define molecular signatures of spermatogenic cells in the common marmoset,Callithrix jacchus. Interestingly,NANOG,PRDM1,DPPA3(STELLA),IFITM3, andZP1transcripts, but noPOU5F1(OCT4), were detected in adult marmoset testis. Conversely, mouse testis expressedPou5f1but notNanog,Prdm1,Dppa3,Ifitm3, andZp1. Other previously described mouse germ cell markers were conserved in marmoset and mouse testes. Intriguingly, marmoset spermatogenic cells underwent dynamic protein expression in a developmental stage-specific manner; DDX4 (VASA) protein was present in gonocytes, diminished in spermatogonial cells, and reexpressed in spermatocytes. To investigate epigenetic differences between adult marmoset and mice, DNA methylation analyses identified unique epigenetic profiles to marmoset and mice. MarmosetNANOGandPOU5F1promoters in spermatogenic cells exhibited a methylation status opposite to that in mice, while theDDX4andLEFTY1loci, as well as imprinted genes, displayed an evolutionarily conserved methylation pattern. Marmosets have great advantages as models for human reproductive biology and are also valuable as experimental nonhuman primates; thus, the current study provides an important platform for primate reproductive biology, including possible applications to humans.