Glyphosate damages blood-testis barrier via NOX1-triggered oxidative stress in rats: Long-term exposure as a potential risk for male reproductive health. (15th January 2022)

• Record Type: Journal Article
• Authors: Liu, Jing-Bo; Li, Zi-Fa; Lu, Lu; Wang, Zhen-Yong; Wang, Lin
• Is Part Of: Environment international. Volume 159(2022)
• Publication Date: 2022-01-15
• Subjects: Glyphosate -- Blood-testis barrier -- Oxidative stress -- NOX1 -- Estrogen receptor-α; ADI Acceptable daily intake -- ES ectoplasmic specialization -- BTB blood-testis barrier -- CCK-8 Cell Counting Kit-8 -- CASA computer-assisted sperm analyzer -- ER-α/β estrogen receptor-α/β -- FBS fetal bovine serum -- GJ gap junction -- GLY glyphosate -- TJ tight junction -- MDA malondialdehyde -- NOX1 NADPH oxidase 1 -- NOAEL no-observed adverse effect level -- qRT-PCR quantitative reverse transcriptional polymerase chain reaction -- ROS reactive oxygen species -- SCs Sertoli cells -- TEM transmission electron microscopy; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2021.107038
• Languages: English
• ISSNs: 0160-4120

Abstract

Graphical abstract: Highlights: Glyphosate (GLY) causes blood-testis barrier (BTB) damage and low-quality sperm. GLY-induced BTB injury contributes to sperm quality decrease. NOX1-derived oxidative stress results in the disruption of BTB integrity. NOX1 upregulation may be due to the interaction of GLY with estrogen receptor-α. Abstract: Blood-testis barrier (BTB) creates a privileged niche indispensable for spermatogenesis. Glyphosate (GLY), the most commonly used herbicide worldwide, has been reported to decrease sperm quality. However, whether and how GLY destroys the BTB to affect sperm quality remains to be elucidated. Herein, this study was designed to investigate the influence of GLY on the BTB in vivo and in vitro experiments. The results showed that male rats exposed to GLY for 4 months exhibited a decrease in sperm quality and quantity, accompanied by BTB integrity disruption and testicular oxidative stress. Additionally, GLY-induced reactive oxygen species (ROS) contributed to the downregulation of BTB-related proteins in primary Sertoli cells (SCs). Intriguingly, we identified a marked upregulation of oxidative stress-related gene NOX1 in GLY-exposed testis based on transcriptome analysis. NOX1 knockdown blocked the GLY-induced oxidative stress, as well as prevented BTB-related protein decrease in SCs. Furthermore, the estrogen receptor (ER)-α was significantly upregulated in vivo and in vitro models. An ER-α inhibitor decreased the expression levels of both ER-α and NOX1. Mechanistically, GLY directly interacted with ER-α at the site of Pro39 and Lys401 to promote ER-α activation, which boosted NOX1 expression to trigger ROS accumulation. Collectively, these results demonstrate that long-term GLY exposure adversely affects BTB integrity, which disrupts spermatogenesis via activation of ER-α/NOX1 axis. This study presents a better understanding of the risk of long-term GLY exposure to male fertility.