Effects of developmental exposure to glyphosate and a glyphosate-based herbicide on the male rat mammary gland

ALTAMIRANO GA; KASS L; GOMEZ AL; MUÑOZ-DE-TORO M; LETURIA J

Mar del Plata

Congreso; LXIII Reunión de la Sociedad Argentina de Investigación Clínica; 2018

Sociedad Argentina de Investigación Clínica

Glyphosateexposure during critical periods of development induces adverse effects on thereproductive system of male rats. Previously, we have shown thatglyphosate-based herbicides (GBHs) produce endocrine-disrupting effects on themale rat mammary gland, and that these effects could be due to the activeprinciple (glyphosate), the adjuvants or both. Here, we evaluated inpostpubertal rats, whetherthe effects on male mammary gland development are caused by glyphosate alone orits combination with adjuvants. Pregnant rats were exposed orally through thediet to vehicle (saline solution), 4 mg/kg/day of glyphosate (GLI) or 4mg/kg/day of GBH from gestational day 9 until weaning. On postnatal day 60, themale offspring were sacrificed and mammary gland samples were collected. Total area, perimeter, longitudinal growth,mammary density and the number of terminal end buds (TEBs) were measured inmammary gland whole-mounts (WMs). Also, estrogen(ESR1) and androgen receptor (AR) mRNA and protein expression were evaluatedand mRNA expression of ESR1 alternative transcripts, cyclin D1 (CCND1),epidermal growth factor receptor (EGFR) and prolactin receptor (PRLR) wereassessed. In addition, the methylation status of ESR1 promoters was analyzed. GLIand GBH reduced mammary gland total area and GBH also decreased the perimeterof the gland and increased the number of TEBs. ESR1 mRNA and protein expressionand ESR1-OS mRNA levels were reduced in both exposed groups, which wasaccompanied by hypermethylation of ESR1-OS promoter. AR mRNA levels were also reducedin both groups; however, its protein expression was higher in GBH-exposedanimals. Besides, CCND1, EGFR and PRLR mRNA expression were lower in GLI andGBH exposed animals. Our results suggest that GBH effects on male rat mammarygland growth and gene expression could be mediated mainly by the active principleof the herbicide.