Neonatal exposure to a glyphosate-based herbicide alters uterine cell proliferation in ewe lamb

ALARCÓN R; INGARAMO PI; MILESI MM; DIOGUARDI G; RIVERA OE; MUÑOZ-DE-TORO M; LUQUE EH

Mar del Plata, Buenos Aires, Argentina

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXVI Reunión de la Sociedad Argentina de Inmunología y Reunión de la Sociedad Argentina de Fisiología; 2018

Sociedad Argentina de Investigación Clínica, Sociedad Argentina de Inmunología y Sociedad Argentina de Fisiología

Glyphosate based herbicides (GBH) are one of the most extensively used pesticides in agriculture all over the world. Recently, we showed that in rats a brief exposure to a low dose of GBH during the first week of life alters uterine development, induces epithelial hyperplasia and causes post-implantation embryo loss. The present study investigates whether a brief postnatal exposure to a low dose of GBH using two different administration routes alters the uterine differentiation of prepubertal ewe lamb. Ewe lambs (Frisone breed) were sc or orally exposed from postnatal day 1 (PND1) to PND14 to saline solution (vehicle) or a low dose of a GBH (glyphosate at 2 mg/Kg/day). At PND45, uterine horns samples were collected for paraffin-embedding or stored at -80°C until mRNA extraction. Cell proliferation was assessed in all uterine compartments by quantifying the expression of Ki-67 protein using immunohistochemistry. RT-PCR was performed to evaluate the expression of genes related with uterine development and differentiation, such as: steroid receptors (ESR1, ESR2 and PR) and insulin-like growth factors (IGF-1, IGF-2 and its receptor IGF-1R). GBH treatment decreased the rate of proliferation in the luminal epithelium (scGBH 6.4±0.9**, oGBH 5.7±0.7** vs C 12.4±2.0, **p