4.3 Article

Transcriptional regulation of PEBP1 expression by androgen receptor in mouse testes

Journal

SYSTEMS BIOLOGY IN REPRODUCTIVE MEDICINE
Volume 68, Issue 1, Pages 70-79

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/19396368.2021.2004471

Keywords

PEBP1; androgen receptor; testis; spermatogenesis

Funding

  1. Natural Science Foundation [31800984]
  2. Guangdong Natural Science Foundation [2018A0303130337]
  3. Shenzhen Science and Technology Planning Project [JCYJ20180228164047023, JCYJ20190808095407464]
  4. Longhua Science and Technology Planning Project [1150A20190513BA7B6B0, 2020006]

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The study verified that Pebp1 is a target gene regulated by androgens and AR in mouse Sertoli cells, with effective androgen-responsive elements (AREs) in the promotor of the Pepb1 gene. Pebp1 is expressed at all stages of testicular development in mice, showing an increasing trend in expression from 1 to 8 weeks postnatal.
Androgen and AR are essential for maintaining spermatogenesis and male fertility. Previous studies have shown that the phosphatidyl ethanolamine binding protein 1 (Pebp1) gene is down-regulated in the selective ablation of the AR in the Sertoli cells of mouse testes compared with wild-type mice, indicating that Pebp1 is a candidate target of AR. The ChIP-PCR data and ChIP-sequencing results of this study verified that Pebp1 is a target gene regulated by AR. Real-time PCR, Western blot analysis, and immunofluorescence data showed that Pebp1 is expressed at all stages of testicular development, with an increasing trend from 1 to 8 weeks of postnatal development. PEBP1 was principally located in the cytoplasm, and high-intensity fluorescence revealed PEBP in the lumen of the testicular tubules. Bioinformatics analysis indicated effective androgen-responsive elements (AREs) located in the promotor of Pepb1 gene. Dual fluorescence assay data showed that androgens and AR could bind to the AREs of Pebp1 and induce an increase of gene expression. These data suggest that Pepb1 is a newfound target gene regulated by androgens and AR in mouse Sertoli cells. However, the detailed molecular mechanism of their role in spermatogenesis still needs to be further studied.

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