Genetic and Cellular Analysis of Male Germ Cell Development

OLASO, ROBERT; HABERT, RENÉ

doi:10.1002/j.1939-4640.2000.tb02114.x

Cited by 49 publications

References 171 publications

(214 reference statements)

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Gonocytes, the forgotten cells of the germ cell lineage

Culty

2009

Birth Defects Research Pt C

222

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Male germ cells, the repository cells of the genome, comprise several successive developmental stages starting in the embryo and ending up with the spermatozoon. Gonocytes represent the fetal and neonatal stages preceding the formation of spermatogonial stem cells. Recent findings shows that germline stem cells can be driven to pluripotency and used as alternative for embryonic stem cells prompted more effort in identifying the processes regulating the development of their precursors, the testicular gonocytes. Also called pre- or pro-spermatogonia, gonocytes represent not one, but several successive developmental stages between the time at which the germ cell becomes resident in the forming fetal testis to the time it migrates to the basement membrane of the seminiferous cord to adopt a spermatogonial phenotype. This review summarizes the findings regarding the genetic identity of gonocytes, providing a description of the "common" gene expression profiles of fetal and neonatal gonocytes, as well as information on the main regulatory factors of gonocyte functions. A better comprehension of gonocyte development should help in the understanding of how germline stem cells are formed, possibly providing valuable clues on the origins of germ cell tumors or infertility.

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Gonocytes, the forgotten cells of the germ cell lineage

Culty

2009

Birth Defects Research Pt C

222

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Characterization of genomic structures and expression profiles of three tandem repeats of a mouse double homeobox gene: Duxbl

Wu¹,

Tsai

Wong

et al. 2010

Developmental Dynamics

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We identified and cloned a mouse double homeobox gene (Duxbl), which encodes two homeodomains. Duxbl gene, a tandem triplicate produces two major transcripts, Duxbl and Duxbl-s. The amino acid sequences of Duxbl homeodomains are most similar to those of human DUX4 protein, associated with facioscapulohumeral muscular dystrophy. In adult tissues, Duxbl is predominantly expressed in female reproductive organs and eyes, and slightly expressed in brain and testes. During gonad development, Duxbl is expressed from embryonic to adult stages and specifically expressed in oocytes and spermatogonia. During embryonic development, Duxbl is transcribed in limbs and tail. However, Duxbl proteins were only detected in trunk and limb muscles and in elongated myocytes and myotubes. In C2C12 muscle cell line, Duxbl expression pattern is similar to differentiated marker gene, Myogenin, increased in expression from 2 days onward in differentiating medium. We suggest that Duxbl proteins play regulatory roles during myogenesis and reproductive developments. Developmental Dynamics 239:927-940,

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Regulation of the proliferation of cocultured gonocytes and sertoli cells by retinoids, triiodothyronine, and intracellular signaling factors: Differences between fetal and neonatal cells

Boulogne

Habert

Levacher

2003

Molecular Reproduction Devel

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The regulation of early fetal germ cell growth has not been studied in cell culture, probably due to the poor survival of these cells. However, cell culture is the only system in which the control of cell growth can be studied independently of the influence of secreted testicular factors, which are diluted in the medium. We successfully cultured dispersed testicular cells from 16.5-day-old rat fetuses in defined medium and compared the growth of these cells with that of cells from 3-day-old neonates. In this system, fetal gonocytes displayed low levels of mitotic activity and their numbers remained stable. In contrast, neonatal gonocytes displayed high levels of mitotic activity and increased in number, these characteristics resembling those observed in vivo. We found that retinoic acid had deleterious effects on the number of gonocytes but did not affect Sertoli cell proliferation in fetal and neonatal cell cultures. Moreover, in fetal cell cultures, the decrease in the number of gonocytes resulted from a decrease in mitotic activity, probably due to a direct effect of retinoids on fetal gonocytes. Among the selective agonists for the retinoic acid receptor (RARalpha agonist, RARbeta agonist, and RARgamma agonist) and the retinoic X receptor (pan-RXR agonist) tested, only the RARalpha agonist reproduced the effects of retinoic acid at concentrations lower than its Kd value in both fetal and neonatal cell cultures. As both RARalpha and RXRalpha are present in fetal and neonatal gonocytes, we suggest that retinoic acid exerts its effects on gonocytes via a RARalpha-RXRalpha heterodimer, with RARalpha functioning as an active partner and RXRalpha as a passive partner. In this culture system, we show for the first time that triiodothyronine (T3) inhibits testicular fetal Sertoli cell and germ cell growth. We also tested intracellular signaling factors and found that a cAMP analog increased Sertoli cell proliferation and germ cell survival in both fetal and neonatal cells whereas phorbol esters (PMA) strongly inhibited the proliferation of fetal but not of neonatal gonocytes. None of the tested factors (T3, dbcAMP, and PMA) seemed to interact with the all-trans retinoic acid pathway. Thus, fetal gonocytes and neonatal gonocytes differ in intrinsic properties, and their growth is not regulated in the same manner. Despite their low level of mitotic activity, fetal gonocytes were more sensitive to various factors than neonatal gonocytes.

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Genetic and Cellular Analysis of Male Germ Cell Development

Cited by 49 publications

References 171 publications

Gonocytes, the forgotten cells of the germ cell lineage

Gonocytes, the forgotten cells of the germ cell lineage

Characterization of genomic structures and expression profiles of three tandem repeats of a mouse double homeobox gene: Duxbl

Regulation of the proliferation of cocultured gonocytes and sertoli cells by retinoids, triiodothyronine, and intracellular signaling factors: Differences between fetal and neonatal cells

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