Gonocytes, from the Fifties to the Present: Is There a Reason to Change the Name?1

Abstract

Historically, the precursor cells to spermatogonia have been identified as "gonocytes," a term created in the fifties to encompass fetal and neonatal germ cells from the time they become resident in testis primordia to the time they relocate at the basement membrane of the seminiferous cords and differentiate. During this period, spreading over several days in rodents and months in humans, germ cell morphology and central location within the cords remain relatively unchanged. Another common trait is the intensive DNA methylation taking place in fetal to neonatal gonocytes. It is only when they reach the periphery of the cords after birth that germ cells acquire the characteristic appearance of spermatogonia. Studies showed that fetal and neonatal germ cells undergo progressive developmental changes comprising three major phases, a fetal mitotic phase followed by a quiescent period during which most of DNA methylation occurs and a neonatal mitotic phase associated with migration to the basement membrane, morphological changes, and differentiation to spermatogonia. Efforts to associate a distinctive gene expression profile to each of these phases have failed, revealing instead gradual changes in gene and protein expression and the coexistence within each period of unsynchronized cells at different phases of development. In the seventies, the terms pre- or prospermatogonia appeared as alternatives for the term gonocytes, but the definition of these terminologies varied between studies. Thus far, the term gonocyte remains the most commonly used, corresponding to a specific location of the cells, morphological appearance, and functional traits, which are distinct from the prior and subsequent developmental phases. In view of the present knowledge, one could further distinguish gonocyte subsets by the prefixes M, Q, and T, describing, respectively, fetal mitotic, quiescent, and transitional neonatal mitotic/migratory gonocytes, in conjunction with emerging methods allowing better discrimination of these subsets.

Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges

“…Owing to the multiple changes occurring in the last phase of gonocyte development, it has been proposed to refer to them as 'transitional' gonocytes (Culty 2013). In the remainder of the review, which focuses on this specific phase of gonocyte development, we will refer to these cells as either 'transitional', or simply as 'gonocytes'.…”

“…A major difference is that rodent testis presents better temporal segregation of germ cell sub-types during perinatal periods than humans or marmosets do. Indeed, despite the heterogeneity of rodent gonocytes and spermatogonial populations, one can still define major developmental phases in which one germ cell type is dominant (Culty 2009(Culty , 2013. By contrast, in human and marmoset, a survey of available data on gene expression profiles, cell behaviors (e.g.…”

“…Gonocytes are the sole source of a functional reservoir of SSCs necessary to ensure life-long production of sperm (Culty 2009(Culty , 2013. Gonocytes encompass a succession of cell types with distinct behaviors that are associated with different fetal and neonatal periods, including a period of fetal mitosis, a phase of quiescence starting around E17.5 in rats and ending at postnatal day 3 (PND3), at which point gonocytes re-enter mitosis and start migrating toward the basement membrane of the seminiferous cords, where they undergo differentiation into SSCs or type A spermatogonia of the first spermatogenic wave (Culty 2009).…”

“…Gonocytes encompass a succession of cell types with distinct behaviors that are associated with different fetal and neonatal periods, including a period of fetal mitosis, a phase of quiescence starting around E17.5 in rats and ending at postnatal day 3 (PND3), at which point gonocytes re-enter mitosis and start migrating toward the basement membrane of the seminiferous cords, where they undergo differentiation into SSCs or type A spermatogonia of the first spermatogenic wave (Culty 2009). These events, which occur 1-2 days earlier in mice, are not precisely synchronized, resulting in the co-existence of quiescent and proliferative gonocytes in neonatal testes (Culty 2013). One common characteristic of fetal and postnatal gonocytes is that they are the site of intense DNA remethylation, required for the acquisition of paternal imprints and transposon silencing (Trasler 2009).…”

Regulation of meiotic entry and gonadal sex differentiation in the human: normal and disrupted signaling

“…Around GW 20, most germ cells present in fetal testes are OCT4-negative; however, a few gonocytes occasionally remain in the testes until 3-4 months of postnatal age (8). From around GW 20, the pre-spermatogonia enter a quiescent phase lasting for the remaining fetal life (28).…”