Producción CyT
Congreso
Autoría
MARTIN, AYELEN
;
Fernandez María Celia
;
Dobladez, Valentina
;
Lombarte Mercedez
;
Brun Lucas
;
Zeni Susana
;
Pennisi, Patricia
Fecha
2025
Editorial y Lugar de Edición
Karger
Resumen
Información suministrada por el agente en
SIGEVA
Glyphosate is an herbicide used in agriculture for weed control. The chronic effects of this herbicide at low doses have been controversial. Its potential to act as an endocrine disruptor, affecting longitudinal growth during postnatal development, remains unknown. OBJECTIVE: To assess the impact of low- dose glyphosate exposure on the development of long bones in juvenile rats. METHODS: Female (16) and male (16) Sprague-Dawley rats were treated daily from day 30 to 70 of age with 1 mg/kg/day o...
Glyphosate is an herbicide used in agriculture for weed control. The chronic effects of this herbicide at low doses have been controversial. Its potential to act as an endocrine disruptor, affecting longitudinal growth during postnatal development, remains unknown. OBJECTIVE: To assess the impact of low- dose glyphosate exposure on the development of long bones in juvenile rats. METHODS: Female (16) and male (16) Sprague-Dawley rats were treated daily from day 30 to 70 of age with 1 mg/kg/day of glyphosate (EPA reference dose, n=8) or saline (n=8) orally. On day 71 blood was collected for measurement of renal, hepatic and hormonal parameters. Bones (hind legs) were harvested for macroscopic, microscopic, microarchitectural (microCT scan), Bone Mineral Density, biomechanic and RNAseq analysis. Liver was processed for IGF1, IGFBP3 and GHR expression. In vitro studies: SaOS-2 cells were cultured in differentiation with/without glyphosate added (10, 50, 100 ng/ml) for matrix deposition and expression profiling studies (col1A1, dmp1, phex, mepe genes) on days 7,14, 21, 28 and 35. RESULTS: No differences were observed in body weight, renal or hepatic parameters, cortisol, E2, To or T3, GHR, IGFBP3 or IGF1 between control and treated animals of both sexes. Tibias´ weight and lenght were similar in treated versus control animals. RNAseq studies showed no differentially expressed genes in females under glyphosate treatment. In treated males, 54 genes were differentially expressed compared to controls (gene groups related to proteolysis, disassembly and organization of the extracellular matrix, collagen catabolic processing, and osteoblast differentiation). Bone Mineral Density was decreased (0.268±0.006 vs 0.253±0,002g/cm2 p<0.03), while Stiffnes and Ultimate Load were higher (S:211±14vs285±23N; UL:78.3±1.5vs84.9±3.2N/mm, p<0.05) in treated males vs control. MicroCT analysis demonstrated increased trabecular separation only in males treated with glyphosate vs control (0.28±0,02 vs 0.35±0,02mm, p<0.03). To enhance our understanding, we conducted experiments ussing a model of osteoblas-to-osteocyte differentiation with SaOS2 cells. When coultured in differentiation media, SaOS2 cells exhibited significantly reduced mineralized matrix deposition (0.704±0.018 vs 0.301±0.169 mMd7; 3.12±0.2 vs 2.27±0.10 mMd14,p<0.05 ANOVA) under glyphosate treatment, which was associated with changes in gene expression profile of differentiated cells. CONCLUSION: Under our experimental conditions, and in contrast to female rats, exposure to low doses of glyphosate alters bone mineral density and bone quality in juvenile male rats, likely through modifications in matrix deposition during bone development.
Ver más
Ver menos
Palabras Clave
GlyphosateBone development