Expression of Concern: Gene trap analysis of germ cell signaling to Sertoli cells: NGF-TrkA mediated induction of Fra1 and Fos by post-meiotic germ cells

Vidal, Francesca; Lopez, Pascal; López-Fernández, Luis Andrés; Ranc, Fariba; Scimeca, Jean‐Claude; Cuzin, François; Rassoulzadegan, Minoo

doi:10.1242/jcs.233692

Cited by 4 publications

(3 citation statements)

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“…WNT signaling has several roles in spermatogenesis, from maintenance to maturation, and thus motility ( 58–60 ). The role of NGF signaling in spermatogenesis in humans is unclear but has been implicated in mammalian Sertoli-germ cell signaling, sperm motility, and the acrosome reaction ( 61 , 62 ). Sperm EGFR activation is a major driver of sperm capacitation ( 63 , 64 ), while Rho GTPases are likely to aid as mediators of the acrosome reaction ( 65 ).…”

Section: Resultsmentioning

confidence: 99%

RNA element discovery from germ cell to blastocyst

Estill

Hauser

Krawetz

2018

Nucleic Acids Research

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Recent studies have shown that tissue-specific transcriptomes contain multiple types of RNAs that are transcribed from intronic and intergenic sequences. The current study presents a tool for the discovery of transcribed, unannotated sequence elements from RNA-seq libraries. This RNA Element (RE) discovery algorithm (REDa) was applied to a spectrum of tissues and cells representing germline, embryonic, and somatic tissues and examined as a function of differentiation through the first set of cell divisions of human development. This highlighted extensive transcription throughout the genome, yielding previously unidentified human spermatogenic RNAs. Both exonic and novel X-chromosome REs were subject to robust meiotic sex chromosome inactivation, although an extensive de-repression occurred in the post-meiotic stages of spermatogenesis. Surprisingly, 2.4% of the 10,395 X chromosome exonic REs were present in mature sperm. Transcribed genomic repetitive sequences, including simple centromeric repeats, HERVE and HSAT1, were also shown to be associated with RE expression during spermatogenesis. These results suggest that pervasive intergenic repetitive sequence expression during human spermatogenesis may play a role in regulating chromatin dynamics. Repetitive REs switching repeat classes during differentiation upon fertilization and embryonic genome activation was evident.

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Section: Resultsmentioning

confidence: 99%

RNA element discovery from germ cell to blastocyst

Estill

Hauser

Krawetz

2018

Nucleic Acids Research

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“…Sertoli cells are in intimate contact with germ cells and control the process of spermatogenesis; they support germ cells structurally and functionally during the process of their differentiation (for review, see Franc ßa et al, 2016). On the other hand, differentiating germ cells signal to Sertoli cells, resulting in a cyclic variation of biochemical properties and gene expression in Sertoli cells (Vidal et al, 2001). Finally, Sertoli-Sertoli cell communication is also required for normal Sertoli cell maturation and spermatogenesis (Sridharan et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Notch signaling regulates nuclear androgen receptor AR and membrane androgen receptor ZIP9 in mouse Sertoli cells

et al. 2019

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Background Notch signaling pathway is involved in contact‐dependent communication between the cells of seminiferous epithelium, and its proper activity is important for undisturbed spermatogenesis. Objectives The aim was to assess the effect of Notch pathway inhibition on the expression of nuclear (AR) and membrane (ZIP9) androgen receptors and androgen‐regulated genes, claudin‐5 and claudin‐11, in TM4 mouse Sertoli cell line. Materials and methods DAPT (γ‐secretase inhibitor) treatment and recombination signal binding protein silencing were employed to reduce Notch signaling, whereas immobilized ligands were used to activate Notch pathway in TM4 cells. To reveal specific effect of each androgen receptor, AR or ZIP9 silencing was performed. Results Notch pathway inhibition increased the expression of AR and ZIP9 mRNA and proteins (p < 0.01; p < 0.05) in TM4 cells, whereas incubation with Notch ligands, rDLL1 or rJAG1, reduced AR (p < 0.01; p < 0.001) and ZIP9 (p < 0.05; p < 0.01) expressions, respectively. Testosterone enhanced the expression of both receptors (p < 0.05; p < 0.01). Androgen‐regulated claudin‐5 and claudin‐11 (p < 0.01; p < 0.001) and cAMP (p < 0.001) were elevated in Notch‐inhibited cells, while activation of Notch signaling by DLL1 or JAG1 reduced claudin‐11 or claudin‐5 level (p < 0.01; p < 0.001), respectively. Discussion Our findings indicate opposite effect of Notch and androgen signaling on the expression of androgen receptors in TM4 cells. We demonstrated that AR expression is regulated by DLL1‐mediated Notch signaling, whereas JAG1 is involved in the regulation of ZIP9. The expression of both claudins and cAMP production is under inhibitory influence of Notch pathway. The effects of Notch signaling on claudin‐5 and claudin‐11 expression are mediated by ZIP9 and AR, respectively. Conclusion Notch signaling may be considered as an important pathway controlling Sertoli cell physiology, and its alterations may contribute to disturbed response of Sertoli cells to androgens.

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“…For this reason, an in vitro culture model of 15P-1 Sertoli cells was employed to investigate the toxicological effects of LMWF in this cell type of the seminiferous epithelium. The 15P-1 Sertoli cell line was characterized originally as Sertoli cells based on their morphology and steroid metabolism [37][38][39]. Since its generation, this cell line has been used in numerous studies with results similar to those obtained using primary cultures of Sertoli cells [40][41][42][43][44][45].…”

Section: Discussionmentioning

confidence: 99%