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Fibroblast Growth Factor 9 Promotes Rat Leydig Cell Development via H3K4me3 Histone Modifications.

Hehua Quan1, Jiayi He1, Feilu Wang1

  • 1Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University; Key Laboratory of Pediatric Anesthesiology (Wenzhou Medical University), Ministry of Education; Key Laboratory of Precision Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, China.

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Summary
This summary is machine-generated.

Fibroblast Growth Factor 9 (FGF9) promotes Leydig cell (LC) proliferation and testosterone production by increasing H3K4me3 histone modifications. This study clarifies FGF9

Keywords:
FGF9H3K4me3 modificationSLCsdevelopmenttestosterone(T)

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Area of Science:

  • Reproductive Biology
  • Endocrinology
  • Epigenetics

Background:

  • Fibroblast Growth Factor 9 (FGF9) is crucial for testis development.
  • Histone modifications, particularly H3K4me3, are implicated in steroidogenesis.
  • The precise role of FGF9 and histone modifications in Leydig cell (LC) differentiation is not fully understood.

Purpose of the Study:

  • To investigate the effect of FGF9 on Leydig cell (LC) differentiation and testosterone synthesis.
  • To explore the involvement of histone modifications, specifically H3K4me3, in FGF9-mediated effects.
  • To elucidate the regulatory mechanisms of FGF9 in the male reproductive system.

Main Methods:

  • Adult male Sprague-Dawley rats were treated with ethane dimethane sulfonate (EDS) to deplete LCs, followed by intratesticular FGF9 injection.
  • Quantitative PCR (qPCR) and Western blot were used to assess gene and protein expression related to testosterone synthesis.
  • Chromatin immunoprecipitation sequencing (ChIP-seq) identified H3K4me3 binding regions.
  • In vitro tubule culture was performed to study FGF9 effects on stem LCs.

Main Results:

  • FGF9 treatment increased serum testosterone levels, LC number, and expression of key steroidogenic genes.
  • FGF9 significantly elevated H3K4me3 levels and reduced H3K9me3 levels.
  • FGF9 promoted H3K4me3 enrichment on the promoter regions of steroidogenic genes (Scarb1, Stard1, Srd5a1).
  • In vitro, FGF9 enhanced testosterone production and stem LC proliferation.

Conclusions:

  • FGF9 stimulates Leydig cell (LC) proliferation and differentiation.
  • FGF9 enhances testosterone production through epigenetic regulation via H3K4me3 modification.
  • These findings highlight FGF9 as a key regulator in testicular function and steroidogenesis.