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Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway [Spry1 KD RNA-Seq]

ABSTRACT: To explore the function of Spry1 in testis, we constructed a mouse model with testicular specific KD of Spry1 through seminiferous tubule transplantation

ORGANISM(S): Mus musculus

PROVIDER: GSE212667 | GEO | 2023/09/01

REPOSITORIES: GEO

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Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway [Dmrt1 RNA-Seq]

Project description:To explore the potential function of Dmrt1 in spermatogenesis, we constructed a Dmrt1-deficiency mouse model by knockdown Dmrt1 in testicular seminiferous tubule specifically

2023-09-01 | GSE212664 | GEO

Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway [Spry1 KD RNA-Seq]

Project description:Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway [Spry1 KD RNA-Seq]

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Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway

Project description:Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway

| PRJNA876713 | ENA

Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway [ChIP-Seq]

Project description:In order to explore the mechanisms of Dmrt1 in regulating testicular immune homeostasis, we performed ChIP-seq analysis on primary SCs infected with a lentiviral vector expressing FLAG-tagged Dmrt1

2023-09-01 | GSE212665 | GEO

Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway [ChIP-Seq]

Project description:Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway [ChIP-Seq]

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Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-09-01 | GSE212668 | GEO

Transcription factor <i>Dmrt1</i> triggers the SPRY1-NF-κB pathway to maintain testicular immune homeostasis and male fertility.

Project description:Bacterial or viral infections, such as Brucella, mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found that Dmrt1 plays an important role in regulating testicular immune homeostasis. Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed that Dmrt1 positively regulated the expression of Spry1, an inhibitory protein of the receptor tyrosine kinase (RTK) signaling pathway. Furthermore, immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) analysis indicated that SPRY1 binds to nuclear factor kappa B1 (NF-κB1) to prevent nuclear translocation of p65, inhibit activation of NF-κB signaling, prevent excessive inflammatory reaction in the testis, and protect the integrity of the blood-testis barrier. In view of this newly identified Dmrt1- Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis, our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.

| S-EPMC10236308 | biostudies-literature

Potency of Testicular Somatic Environment to Support Spermatogenesis in XX/Sry Transgenic Male Mice

Project description:Sry is sufficient to induce testis formation and subsequent male development of internal and external genitalia in chromosomally female mice and humans. In XX sex-reversed males such as XX/Sry-transgenic (XX/Sry) mice, however, testicular germ cells always disappear soon after birth due to germ cell autonomous defects. Therefore, it remains unclear whether or not Sry alone is sufficient to induce a fully functional testicular soma capable of supporting complete spermatogenesis in the XX body. Here we demonstrated that the testicular somatic environment of XX/Sry males is defective in the later phases of spermatogenesis. Spermatogonial transplantation analyses using XX/Sry male mice revealed that donor XY spermatogonia are capable of proliferating, entering meiosis and differentiating into the round spermatid stage. XY donor-derived round spermatids, however, were frequently detached from the XX/Sry seminiferous epithelia and underwent cell death, thereby preventing further progress beyond the elongated spermatid stage. In contrast, immature XY seminiferous tubule segments transplanted under XX/Sry testis capsules clearly displayed proper differentiation into elongated spermatids in the transplanted XY donor tubules. Microarray analysis of seminiferous tubules isolated from XX/Sry testes confirmed missing expression of several Y-linked genes and alterations in the expression profile of genes associated with spermatogenesis. Therefore, our findings indicate dysfunction of the somatic tubule components, probably Sertoli cells, of XX/Sry testes, supporting our hypothesis that Sry alone is insufficient to induce a fully functional Sertoli cell in XX mice. Keywords: comparative genomic hybridization

2007-07-15 | GSE5319 | GEO

Next-generation sequencing to characterize the molecular basis for the differentiation of ES cells into testicular somatic cell-like cells and germ cell-like cells

Project description:Taking advantage of the tesco-cfp transgenic mouse line in which CFP is exclusively expressed in Sertoli cells under the control of a testis-specific enhancer (tesco), we established an embryonic stem cell from the mouse line (i.e. tcESC). We also created tcESC constitutively expressing mouse Sf1 transgene (tc;Sf1ESC). When we induced the differentiation of the two ESC lines into testicular somatic cell-like cells (TesLCs), tc;Sf1ESCs efficiently developed seminiferous tubule-like structures with the appearance of CFP-positive Setoli cell-like cells (SCLCs) in the tubules. On the other hand, epiblast-like cells (EpiLCs) were generated from ESCs having a germ cell-specific Prdm1-gfp transgene. Co-culture of tc;Sf1TesLCs with Prdm1-gfp EpiLCs resulted in self-organised aggregates, or testicular organoids. In the organoid, the EpiLCs differentiated into GFP-positive PGCLCs or gonocyte-like cells that were enclosed within a seminiferous tubule-like structure composed of CFP-positive SCLCs.

2021-06-18 | GSE149932 | GEO

Proteomic Analysis of Spry1-Amh-cre Conditional Knockout Mouse Testis

Project description:To investigate the important role of Spry1 gene in mouse testicular development, spermatogenesis, and immune homeostasis by conditionally knocking out Spry1 in Sertoli cells of testes.

2023-08-24 | PXD044823 |

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