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Low Doses of Glyphosate/Roundup Alter Blood-Testis Barrier Integrity in Juvenile Rats.

ABSTRACT: It has been postulated that glyphosate (G) or its commercial formulation Roundup (R) might lead to male fertility impairment. In this study, we investigated the possible effects of G or R treatment of juvenile male rats on blood-testis barrier function and on adult male sperm production. Pups were randomly assigned to the following groups: control group (C), receiving water; G2 and G50 groups, receiving 2 and 50 mg/kg/day G respectively; and R2 and R50 groups receiving 2 and 50 mg/kg/day R respectively. Treatments were performed orally from postnatal day (PND) 14 to 30, period of life that is essential to complete a functional blood-testis barrier. Evaluation was done on PND 31. No differences in body and testis weight were observed between groups. Testis histological analysis showed disorganized seminiferous epithelium, with apparent low cellular adhesion in treated animals. Blood-testis barrier permeability to a biotin tracer was examined. A significant increase in permeable tubules was observed in treated groups. To evaluate possible mechanisms that could explain the effects on blood-testis barrier permeability, intratesticular testosterone levels, androgen receptor expression, thiobarbituric acid reactive substances (TBARS) and the expression of intercellular junction proteins (claudin11, occludin, ZO-1, connexin43, 46, and 50 which are components of the blood-testis barrier) were examined. No modifications in the above-mentioned parameters were detected. To evaluate whether juvenile exposure to G and R could have consequences during adulthood, a set of animals of the R50 group was allowed to grow up until PND 90. Histological analysis showed that control and R50 groups had normal cellular associations and complete spermatogenesis. Also, blood-testis barrier function was recovered and testicular weight, daily sperm production, and epididymal sperm motility and morphology did not seem to be modified by juvenile treatment. In conclusion, the results presented herein show that continuous exposure to low doses of G or R alters blood-testis barrier permeability in juvenile rats. However, considering that adult animals treated during the juvenile stage showed no differences in daily sperm production compared with control animals, it is feasible to think that blood-testis barrier impairment is a reversible phenomenon. More studies are needed to determine possible damage in the reproductive function of human juvenile populations exposed to low doses of G or R.

SUBMITTER: Gorga A

PROVIDER: S-EPMC7992013 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:This study aimed to investigate the hepatic transcriptional response of brown trout to glyphosate, and its formulated product, Roundup. We exposed juvenile female brown trout to three concentrations of glyphosate (0.01, 0.5 and 10 mg/L) and Roundup (0.01, 0.5 and 10 mg/L glyphosate acid equivalent) for 14 days and sequenced the hepatic transcriptome of 6 individual females per treatment group in order to determine the global mechanisms of toxicity of this widely used herbicide. We assembled the brown trout transcriptome using an optimised de novo approach, and subsequent differential expression analysis identified a total of 1020 differentially-regulated transcripts across all treatments. Differentially-expressed transcripts included those encoding components of the antioxidant system, a number of stress-response proteins and pro-apoptotic signalling molecules. Functional analysis also revealed over-representation of pathways involved in regulation of cell-proliferation and turnover, and up-regulation of energy metabolism and other metabolic processes. Together, these transcriptional changes are consistent with generation of oxidative stress and the widespread induction of compensatory cellular stress response pathways. The mechanisms of toxicity identified were similar across both glyphosate and Roundup treatments, including for environmentally relevant concentrations. The significant alterations in transcript expression observed at the lowest concentrations tested raises concerns for the toxicity of this herbicide to fish populations inhabiting contaminated rivers. Fish were exposed to 3 concentrations of glyphosate (0.01, 0.1 and 10 mg/L), 3 concentrations of Roundup (0.01, 0.5 and 10 mg/L glyphosate acid equivalent) and water controls for 14 days. Liver mRNA from 6 replicate individuals per treatment was sequenced in an Illumina HiSeq 2500 platform. Two control groups (n=6 fish per group) were included. Using a de novo approach, we assembled the hepatic transcriptome for brown trout. Sequence reads were re-mapped to the assembled transcriptome using Bowtie2 and transcript expression profiling was conducted using EdgeR. ERCC spike controls were added to all individual samples, allowing for the assessment of the reproducibility and dynamic range for transcript expression quantification in our experiments. For the group exposed to 0.1 mg/L glyphosate, only 3 females were available to sequence and the variability between individuals was very high with 1 female identified as an outlier. For this reason, data from this treatment group was deemed unreliable and excluded from the analysis.

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Low Doses of Glyphosate/Roundup Alter Blood-Testis Barrier Integrity in Juvenile Rats.

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