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Fluorochloridone perturbs blood-testis barrier/Sertoli cell barrier function through Arp3-mediated F-actin disruption

Luqing Liu1, Yubin Zhang1, Xiuli Chang1

  • 1School of Public Health, MOE Key Laboratory for Public Health Safety, Key Laboratory of Health Technology Assessment of National Health Commission, Fudan University, Shanghai 200032, China.

Toxicology Letters
|July 9, 2018
PubMed

Insights

Fluorochloridone (FLC) exposure damages male reproductive health by disrupting the blood-testis barrier (BTB) and Sertoli cell barrier integrity. This toxicity is linked to F-actin disorganization mediated by Arp3.

Area of Science:

  • Reproductive Toxicology
  • Cell Biology
  • Molecular Mechanisms

Background:

  • Fluorochloridone (FLC) is associated with male reproductive toxicity.
  • The precise toxicological mechanisms underlying FLC's effects on male reproduction are not fully understood.
  • Investigating the impact on the blood-testis barrier (BTB) and Sertoli cell function is crucial.

Purpose of the Study:

  • To elucidate the toxicological mechanisms of FLC on male reproductive toxicity.
  • To investigate the effects of FLC on the integrity of the blood-testis barrier (BTB) and Sertoli cell barrier.
  • To explore the molecular pathways involved in FLC-induced reproductive damage.

Main Methods:

  • Male rats were administered FLC (30 mg/kg/d) via gavage for 14 days.
  • Primary cultured Sertoli cells were treated with FLC (0-10 μM) in vitro for 24 hours.
  • Evaluated testicular injury, sperm quality, BTB integrity, F-actin organization, and protein expressions (claudin-11, Arp3, occludin, ZO-1, connexin-43).

Main Results:

  • FLC exposure induced time-dependent testicular injuries and decreased sperm quality in vivo.
  • FLC disrupted BTB integrity, altered F-actin organization, and affected claudin-11 and Arp3 expression.
  • In vitro, FLC decreased Sertoli cell barrier tightness and protein expressions of key junctional proteins and Arp3 in a dose- and time-dependent manner.
  • Arp3 overexpression partially rescued FLC-induced alterations in Sertoli cell barrier and F-actin.

Conclusions:

  • FLC exposure significantly impairs male reproductive function.
  • FLC perturbs BTB and Sertoli cell barrier integrity.
  • The mechanism involves Arp3-mediated F-actin disorganization, highlighting Arp3 as a key player in FLC toxicity.
Keywords:
Arp3Blood-testis barrierF-actinFluorochloridoneSertoli cell

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