Peritubular Myoid Cells Are Not the Migrating Population Required for Testis Cord Formation in the XY Gonad

Cool, Jonah; Carmona, F. David; Szucsik, John C.; Capel, Blanche

doi:10.1159/000143430

Cited by 95 publications

(102 citation statements)

References 23 publications

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“…Steroidogenic cells of the developing gonad are initially bipotential; in a testis they are triggered to develop as Leydig cells, while in the ovary they become theca cells. A malespecific migration of mesonephric cells, particularly endothelial cells, into the developing testis contributes to formation of the testis cords that eventually enclose the germ cells (Cool et al 2008, Combes et al 2009). …”

Section: Bipotential Germ Cells In the Genital Ridgesmentioning

confidence: 99%

Sex determination in mammalian germ cells: extrinsic versus intrinsic factors

Bowles

Koopman²

2010

Reproduction

105

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Mammalian germ cells do not determine their sexual fate based on their XX or XY chromosomal constitution. Instead, sexual fate is dependent on the gonadal environment in which they develop. In a fetal testis, germ cells commit to the spermatogenic programme of development during fetal life, although they do not enter meiosis until puberty. In a fetal ovary, germ cells commit to oogenesis by entering prophase of meiosis I. Although it was believed previously that germ cells are pre-programmed to enter meiosis unless they are actively prevented from doing so, recent results indicate that meiosis is triggered by a signaling molecule, retinoic acid (RA). Meiosis is avoided in the fetal testis because a male-specifically expressed enzyme actively degrades RA during the critical time period. Additional extrinsic factors are likely to influence sexual fate of the germ cells, and in particular, we postulate that an additional male-specific fate-determining factor or factors is involved. The full complement of intrinsic factors that underlie the competence of gonadal germ cells to respond to RA and other extrinsic factors is yet to be defined.

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Section: Bipotential Germ Cells In the Genital Ridgesmentioning

confidence: 99%

Sex determination in mammalian germ cells: extrinsic versus intrinsic factors

Bowles

Koopman²

2010

Reproduction

105

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“…They drive the differentiation of other cell types by the expression and secretion of essential factors, many of which are directly upregulated by SOX9 or have been at least suggested to be transcriptionally regulated by SOX9 (see below and for review see Svingen & Koopman (2013)). Overall, it induces global cellular and morphological changes, including the migration of endothelial cells from the mesonephros to form the testis-specific vasculature, an increase in proliferation and the formation of testis cords, which comprise clusters of PGCs surrounded by Sertoli cells (Martineau et al 1997, Capel et al 1999, Schmahl et al 2000, Schmahl & Capel 2003, Cool et al 2008, Combes et al 2009), resulting in the formation of a testis.…”

Section: Regulation Of Mirna Expression By Sox9 During Mammalian Sertmentioning

confidence: 99%

The role of non-coding RNAs in male sex determination and differentiation

2015

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A complex network of gene regulation and interaction drives male sex determination and differentiation. While many important proteincoding genes that are necessary for proper male development have been identified, many disorders in human sex development are still unexplained at the molecular level. This suggests that key factors and regulatory mechanisms are still unknown. In recent years, extensive data have shown that different classes of non-coding RNAs (ncRNAs) play a role in almost all developmental and physiological pathways.Here we review what is known about their role in male sex determination and differentiation not only in mammals, but also other species. While for some processes a key role for ncRNA has been identified, we are still far from having a complete picture.Reproduction (2015) 150 R93-R107

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“…Our results suggest that androgens maintain/promote differentiation of the PTM cell population in our cultures; however, we found no evidence of crosstalk with the SC population. Although it was previously proposed that fetal PTM cells arise from a population of cells migrating into the testis from the mesonephros (Buehr et al 1993), this is now disputed (Cool et al 2008) and further studies are therefore required to determine the impact of androgens on gene expression in fetal PTM cells.…”

Section: Meangsemmentioning

confidence: 99%

“…The interstitial compartment also contains many cells thought to be undifferentiated fibroblasts as well as cells of the vasculature including endothelial cells (Brennan & Capel 2004, Cool et al 2008. The PTM cells surrounding the testis cords express myofibroblast proteins including a-smooth muscle actin (ACTA2) and desmin (DES; Nishino et al 2001).…”

Section: Introductionmentioning

confidence: 99%

“…The PTM cells surrounding the testis cords express myofibroblast proteins including a-smooth muscle actin (ACTA2) and desmin (DES; Nishino et al 2001). PTM cells were originally thought to migrate into the testis from the mesonephros but recent evidence suggests that differentiate from interstitial precursors within the gonad (Cool et al 2008). With endothelial cells identified as the migrating cell population important for formation of testis cords, the precise role played by PTM in fetal life requires re-evaluation (Combes et al 2009).…”

Section: Introductionmentioning

confidence: 99%

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Establishment of long-term monolayer cultures of somatic cells from human fetal testes and expansion of peritubular myoid cells in the presence of androgen

Cowan¹,

Childs²,

Anderson³

et al. 2010

Reproduction

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The somatic (Sertoli cell (SC), Leydig cell (LC), and peritubular myoid (PTM) cell) cells play key roles in development of the fetal testis. We established monolayer cultures from second trimester human testes and investigated the pattern of expression of cell-lineage characteristic mRNAs. Expression of some SC-associated genes (SRY, SOX9, WT1, GATA4, and SF1) was detectable up to and including passage 3 (P3), while others (anti-Mü llerian hormone; desert hedgehog) present prior to dissociation were not expressed in the cultured cells. Transcripts encoding the androgen receptor were expressed but addition of dihydrotestosterone (DHT) had no impact on expression of mRNAs expressed in SC or LC. Total concentrations of mRNAs encoding smooth muscle actin (ACTA2) and desmin increased from P1 to P3; an increasing proportion of the cells in the cultures were immunopositive for ACTA2 consistent with proliferation/differentiation of PTM cells. In conclusion, somatic cell monolayer cultures were established from human fetal testes; these cultures could form the basis for future studies based on isolation of purified populations of somatic cells and manipulation of gene expression that is difficult to achieve with organ culture systems. Our results suggest that fetal SC do not maintain a fully differentiated phenotype in vitro, yet PTM (ACTA2 positive) cells readily adapt to monolayer culture conditions in the presence of DHT. This culture system provides an opportunity to study the impact of regulatory factors on gene expression in PTM cells, a population thought to play a key role in mediating androgen action within the developing testis.

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Peritubular Myoid Cells Are Not the Migrating Population Required for Testis Cord Formation in the XY Gonad

Cited by 95 publications

References 23 publications

Sex determination in mammalian germ cells: extrinsic versus intrinsic factors

Sex determination in mammalian germ cells: extrinsic versus intrinsic factors

The role of non-coding RNAs in male sex determination and differentiation

Establishment of long-term monolayer cultures of somatic cells from human fetal testes and expansion of peritubular myoid cells in the presence of androgen

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