The traditional Chinese medicine Qiangjing tablet prevents blood‐testis barrier injury induced by CdCl₂ through the PI3K/Akt/Rictor signaling pathway

Abstract

Objective Environmental contaminants such as cadmium (Cd) may have a deleterious impact on sperm and reduce male fertility by compromising the blood‐testis barrier (BTB). Hence, the effects of the traditional Chinese medicine Qiangjing tablet (QJP) on sperm quality and BTB alterations induced by Cd in mouse testes were examined. Methods Adult KM mice challenged with Cd chloride were examined, QJP was administered to mice as an oral drug by gavage, and the experiments lasted 2 weeks. Testicular and epididymal weights, sperm quality, anti‐sperm antibodies (AsAb), hormone levels, and histology were evaluated. Changes in the levels of N‐cadherin, occludin, ZO‐1, claudin‐11, F‐actin, and β‐tubulin and their mRNAs were evaluated. The effects of QJP on the PI3K/Akt/Rictor pathway were evaluated. Results CdCl2 decreased reproductive organ weight, sperm quality, and testosterone (T) levels; increased AsAb, follicle‐stimulating hormone (FSH), and luteinizing hormone (LH) levels; induced structural damage in testicles with BTB disruption; increased BTB permeability; and decreased N‐cadherin, occludin, ZO‐1, claudin‐11, F‐actin, and β‐tubulin expression. After treatment, QJP blocked the effects of Cd on reproductive organ weight, sperm quality, and T; mitigated germinal epithelium compartment alterations; decreased AsAb, FSH, and LH levels; and preserved BTB ultrastructure and function. In addition, QJP induced increases in N‐cadherin, occludin, ZO‐1, claudin‐11, F‐actin, and β‐tubulin levels and the expression of their mRNAs through the PI3K/Akt/Rictor pathway. After the application of JRAB2011, the levels of a specific mTORC2 suppressor, Rictor, and the BTB‐protective effect of QJP were greatly reduced. Conclusions We demonstrated the effect of QJP against Cd‐induced damage to the BTB, and the results indicate that QJP may play a significant role in opposing the effects of Cd through the PI3K/Akt/Rictor pathway.

What do we know about blood-testis barrier? current understanding of its structure and physiology

“…Cadmium also affects BTB by reducing occludin expression in mice ( Zhou et al, 2022 ) and altering the localization of Cx43 and occludin in rats. A recent study shows that a traditional Chinese medicine prevented Cd-induced BTB damage opposing to Cd-effects on the PI3K/Akt/Rictor signaling pathway (RICTOR, the rapamycin-insensitive companion of mTOR, is the scaffold protein for substrate binding to mTORC2, which promotes BTB integrity) ( Shen et al, 2023 ).…”