NEONATAL EXPOSURE TO A GLYPHOSATEBASED HERBICIDE ALTERS CELL PROLIFERATION IN THE UTERUS OF EWE LAMBS

ALARCÓN R.; DIOGUARDI, GISELA H.; LUQUE EH; INGARAMO, PAOLA I.; RIVERA, OSCAR E.; MILESI M.; MUÑÓZ DE TORO M

Congreso; Reunión Anual de la sociedad Argentina de Investigación Clínica; 2019

Abstract/Resumen: The increasing use of glyphosate-basedherbicides (GBHs) raised concern about its effects on animal andhuman health. Recently, we reported that postnatal exposure ofewe lambs to a low dose of GBH decreased the uterine cellproliferation, regardless the oral or subcutaneous (sc)administration route. Here, we investigate the molecularpathways related to uterine cell proliferation affected by apostnatal GBH exposure. Frisone ewe lambs were sc exposedfrom PND1 to PND14 to vehicle (control) or a low dose of a GBH(glyphosate at 2 mg/Kg/day). At postnatal day 45 (PND45),uterine horns were collected for paraffin-embedding or stored at-80°C until mRNA extraction. Expression of Ki67 (as cellproliferation marker), p27 and proteins involved in uterinedevelopment (ERa, PR, Wnt5a, Wnt7a, ß-catenin, Hoxa10 andFoxa2) were evaluated by immunohistochemistry. Geneexpression of insulin-like growth factors (IGF-1, IGF-2), itsreceptor (IGF-1R) and the binding protein (IGFBP-3), also relatedto uterine development, were assessed by RT-PCR. Cellproliferation decreased while p27 expression increased in alluterine compartments: luminal (LE) and glandular (GE) epithelia,subepithelial stroma (SS) and myometrium. The mRNAexpression of IGFBP-3 was also increased in GBH-exposed lambs.In addition, lower ERa expression was observed in LE, GE andSS; while PR expression was lower in LE, and higher in GE andSS vs control. Moreover, GBH exposure decreased the expressionof Wnt5a in GE and Wnt7a in SS; whereas ß-catenin expressionwas lower in LE and GE. In GBH-exposed lambs a decreasedHoxa10 and Foxa2 expression in SS and GE, respectively, wasalso detected. To conclude, postnatal exposure to anenvironmental relevant dose of GBH decrease the cellproliferation in prepubertal sheep uterus by disrupting theexpression of molecules responsible of uterine development. Ourresults suggest that GBH exposure could compromisereproductive performance in livestock animals.