Perinatal Exposure to Glyphosate and Propiconazole Impairs the Development of the Male Rat Mammary Gland

GOMEZ AL; ALTAMIRANO GA; SCHIERANO-MAROTTI G; MUÑOZ-DE-TORO M; KASS L

Modalidad Virtual

Congreso; 8th Latin American Pesticide Residue Workshop; 2021

Ministerio de Desarrollo Agropecuario MIDA, Panamá. Universidad Nacional del Litoral-UNL, Argentina

Exposure to Glyphosate (GLY) during critical developmental periods induces adverse effects on the reproductive system of male rats, and we have shown that glyphosate-based herbicides produce endocrine-disrupting effects on the male rat mammary gland. On the other hand, propiconazole (PRO) has been shown to cause alterations in steroidogenesis and to be a hepatotoxic compound, which could alter the hepatic response to xenobiotics and, therefore, modify the effects induced by GLY when a mixture of both agrochemicals is used. Here, our aim was to evaluate whether developmental exposure to PRO, GLY or both (PROGLY) alter mammary gland development in postpubertal male rats. Pregnant rats were orally exposed to vehicle (saline solution), 4 mg/kg/day of PRO, 4 mg/kg/day of GLY, or a mixture of PRO and GLY (each 4 mg/kg/day), from gestation day 9 until weaning. On postnatal day 60, male offspring were euthanized, and mammary gland samples were collected. Total area, perimeter, longitudinal growth, number of terminal end buds and mammary developmental score were analyzed in mammary gland whole-mounts (WMs). Lobuloalveolar development and the presence of hyperplastic structures were evaluated in histological sections, as well as proliferation (Ki67) and protein expression of estrogen receptor alpha (ESR1), androgen receptor (AR) and aromatase (ARO). In addition, the mRNA expression of ARO, cyclin D1 (Ccnd1) and Wnt5a was assessed. Among the parameters evaluated in WM, only the total area of the mammary gland was affected in the exposed animals and it was reduced in the males exposed to GLY (Control: 492±16 mm2, GLY: 419±21 mm2, PRO: 436±17 mm2, PROGLY: 473±19 mm2; Control vs GLY p