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Isolation of Sertoli Cells and Peritubular Cells from Rat Testes
11:11

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Published on: February 8, 2016

Activin signaling regulates Sertoli cell differentiation and function.

Peter K Nicholls1, Peter G Stanton, Justin L Chen

  • 1Prince Henry's Institute of Medical Research, Clayton 3168, Victoria, Australia.

Endocrinology
|November 3, 2012
PubMed
Summary

Activin A signaling can reprogram mature testicular Sertoli cells back to an immature state, disrupting spermatogenesis. This finding highlights the critical need to control activin A levels in adult males.

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Area of Science:

  • Reproductive Biology
  • Cellular Biology
  • Endocrinology

Background:

  • Activin A signaling promotes Sertoli cell proliferation and inhibits differentiation during development.
  • Decreased activin A levels at puberty are essential for Sertoli cell differentiation and spermatogenesis support.

Purpose of the Study:

  • To investigate if terminally differentiated Sertoli cells can revert to an immature phenotype when exposed to elevated activin A levels.
  • To identify the role of activin A in adult Sertoli cell function and spermatogenesis.

Main Methods:

  • Adeno-associated virus (rAAV6) expressing activin A was used to increase systemic activin levels in adult mice.
  • Measurements included testis mass, blood-testis barrier function (permeability tracers, transepithelial electrical resistance), and cell proliferation (5-ethynyl-2'-deoxyuridine incorporation).
  • Expression of Sertoli cell markers (cytokeratin-18, claudin-11) was analyzed.

Main Results:

  • Chronic activin A signaling significantly reduced testis mass and induced hypospermatogenesis.
  • Activin A disrupted blood-testis barrier integrity and tight junction formation in Sertoli cells.
  • Increased activin A reinitiated Sertoli cell proliferation and altered marker expression, reverting cells to a juvenile phenotype.

Conclusions:

  • Activin A is the first identified factor capable of dedifferentiating mature Sertoli cells.
  • Strict control of activin A signaling in adults is crucial for maintaining Sertoli cell function and supporting spermatogenesis.