Neonatal exposure of ewe lambs to a glyphosate-based herbicide alters the expression of proteins involved in uterine development and differentiation

MILESI MM; BELMONTE N; ALARCON R; DIODUARDI GH; LUQUE EH.; RIVERA OE,; MUÑOZ DE TORO M,

Mar del Plata

Congreso; LXI Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

SAIC

Glyphosate-based herbicides (GBH) are one of the mostemployed agrochemicals around the world. Recently, we showed that, in the rat,developmental exposure to a GBH alters uterine organogeneticdifferentiation showing hyperplasia in prepubertal samples and inducing post-implantationembryo loss. No reports are available regarding GBH effects on thereproductive system of the ewe lamb. This study investigates the effects of abrief postnatal exposure to a GBH on the morphology and differentiation of the prepuberalsheep uterus. Ewe lambs (Frizone breed) were sc injected from postnatal day 1(PND1) to PND14 with saline solution (vehicle) or 2mg/Kg/day of a GBH. On PND45 ewe lambs were hysterectomized and uterine sampleswere paraffin-embedded. In trichrome stained sections morphological parameterswere evaluated: luminal epithelial height, glandular density, and thickness ofthe subepithelial stroma and myometrium. Immunohistochemistry was performed to quantifythe uterine expression of Ki-67 (as cellular proliferation marker) and proteinsinvolved in uterine development and differentiation, such as: estrogen receptorα (ERα), progesterone receptor (PR), Wnt7a and β-catenin. GBH treatment did notalter uterine morphology, but reduced the proliferation rate in thesubepithelial stroma, and in the luminal and glandular epithelium. Thedecrease in cell proliferation was associated with a downregulation of ERαexpression in the same compartments. PR expression was increased in theglandular epithelium and in the subepithelial stroma, and downregulated in theluminal epithelium. GBH group also showed a decrease in Wnt7a expression in thesubepithelial stroma and a downregulation in β-catenin expression in theluminal and glandular epithelium. Exposure to a low dose of a GBH during earlypostnatal development decreased uterine proliferation and disrupted theexpression of morphoregulatory proteins in prepubertal sheep. All thesealterations might impair female fertility at adulthood.