mTORC1/rpS6 and spermatogenic function in the testis—insights from the adjudin model

S. Wu, Ming Yan, L. Li, Baiping Mao, Chris K C WONG, Renshan Ge, Qingquan Lian, C. Yan Cheng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

mTORC1/rpS6 signaling complex promoted Sertoli blood-testis barrier (BTB) remodeling by perturbing Sertoli cell-cell adhesion site known as the basal ectoplasmic specialization (ES). mTORC1/rpS6 complex also promoted disruption of spermatid adhesion at the Sertoli-spermatid interface called the apical ES. Herein, we performed analyses using the adjudin (a non-hormonal male contraceptive drug under development) model, wherein adjudin was known to perturb apical and basal ES function when used at high dose. Through direct administration of adjudin to the testis, adjudin at doses that failed to perturb BTB integrity per se, overexpression of an rpS6 phosphomimetic (i.e., constitutively active) mutant (i.e., p-rpS6-MT) that modified BTB function considerably potentiated adjudin efficacy. This led to disorderly spatial expression of proteins necessary to maintain the proper cytoskeletal organization of F-actin and microtubules (MTs) across the seminiferous epithelium, leading to germ cell exfoliation and aspermatogenesis. These findings yielded important insights regarding the role of mTORC1/rpS6 signaling complex in regulating BTB homeostasis.

Original languageEnglish
Pages (from-to)54-66
Number of pages13
JournalReproductive Toxicology
Volume89
DOIs
Publication statusPublished - Oct 2019

Scopus Subject Areas

  • Toxicology

User-Defined Keywords

  • Adjudin
  • Blood-Testis barrier
  • F5-peptide
  • mTORC1/rpS6 signaling complex
  • p-rpS6 mutant
  • Spermatogenesis
  • Testis

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