The apical ES-BTB-BM functional axis is an emerging target for toxicant-induced infertility

Hin Ting Wan, Dolores D. Mruk, Chris K C WONG, C. Yan Cheng*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

34 Citations (Scopus)


Testes are sensitive to toxicants, such as cadmium and phthalates, which disrupt a local functional axis in the seminiferous epithelium known as the 'apical ectoplasmic specialization (apical ES)-blood-testis barrier (BTB)-basement membrane (BM)'. Following exposure, toxicants contact the basement membrane and activate the Sertoli cell, which perturbs its signaling function. Thus, toxicants can modulate signaling and/or cellular events at the apical ES-BTB-BM axis, perturbing spermatogenesis without entering the epithelium. Toxicants also enter the epithelium via drug transporters to potentiate their damaging effects, and downregulation of efflux transporters by toxicants impedes BTB function such that toxicants remain in the epithelium and efficiently disrupt spermatogenesis. These findings support a novel model of toxicant-induced disruption of spermatogenesis that could be interfered with using small molecules.

Original languageEnglish
Pages (from-to)396-405
Number of pages10
JournalTrends in Molecular Medicine
Issue number7
Publication statusPublished - Jul 2013

Scopus Subject Areas

  • Molecular Medicine
  • Molecular Biology


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