EFFECTS OF DEVELOPMENTAL EXPOSURE TO GLYPHOSATE AND A GLYPHOSATE-BASED HERBICIDE ON THE MALE RAT MAMMARY GLAND

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

Mar del Plata

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

Sociedad Argentina de Investigación Clínica

Glyphosate exposure during critical periods of development induces adverse effects on the reproductive system of male rats. Previously, we have shown that glyphosate-based herbicides (GBHs) produce endocrine-disrupting effects on the male rat mammary gland, and that these effects could be due to the active principle (glyphosate), the adjuvants or both. Here, we evaluated in postpubertal rats, whether the effects on male mammary gland development are caused by glyphosate alone or its combination with adjuvants. Pregnant rats were exposed orally through the diet to vehicle (saline solution), 4 mg/kg/day of glyphosate (GLI) or 4 mg/kg/day of GBH from gestational day 9 until weaning. On postnatal day 60, the male 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 in mammary gland whole-mounts (WMs). Also, estrogen (ESR1) and androgen receptor (AR) mRNA and protein expression were evaluated and mRNA expression of ESR1 alternative transcripts, cyclin D1 (CCND1), epidermal growth factor receptor (EGFR) and prolactin receptor (PRLR) were assessed. In addition, the methylation status of ESR1 promoters was analyzed. GLI and GBH reduced mammary gland total area and GBH also decreased the perimeter of the gland and increased the number of TEBs. ESR1 mRNA and protein expression and ESR1-OS mRNA levels were reduced in both exposed groups, which was accompanied by hypermethylation of ESR1-OS promoter. AR mRNA levels were also reduced in both groups; however, its protein expression was higher in GBH-exposed animals. Besides, CCND1, EGFR and PRLR mRNA expression were lower in GLI and GBH exposed animals. Our results suggest that GBH effects on male rat mammary gland growth and gene expression could be mediated mainly by the active principle of the herbicide.