Neonatal exposure of ewe lambs to a glyphosate-based herbicide adversely affects the expression of genes involved in ovarian follicular development independently of administration route

INGARAMO PI; ALARCÓN R; RIVERA OE; DIOGUARDI G; BELMONTE N; 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

The exposure of ewe lambs to endocrine disruptors compounds (EDC) may alter ovarian development. Previously we demonstrate that Glyphosate-based herbicides (GBH) alters follicular development. Our hypothesis suggests that exposure of ewe lambs during an early postnatal development to GBH may modify the ovarian gene expression after in the prepubertal stage. The aim of the present study was to compare the effect of oral and subcutaneous exposure to a GBH on the expression of ovarian genes. Ewe lambs were exposed from postnatal day (PND) 1 to PND14 to subcutaneous (n: 5) or orally (n: 5) environmentally relevant doses of Glyphosate in Argentina (2 mg/Kg/day) and controls (n: 12) with saline solution. On PND45, the ovaries were sectioned and immediately frozen in liquid nitrogen and stored at -80 °C for the future RNA extraction. The mRNA expression of following genes involved in follicular development were evaluated: ESR1, estrogen receptor β (ESR2), progesterone receptor (PR), follicle-stimulating hormone receptor (FSHR), bone morphogenetic protein 15 (BMP15), BMP receptor 1B (BMPR1B), growth and differentiation factor 9 (GDF9), insulin-like growth factor 2 (IGF-2). The mRNA expression of β-Actin protein was used as housekeeping gene. Results were expressed as mRNA relative expression to control group (C=1). Lambs exposed to GBH showed a reduction of FSHR (scGBH=0.45±0.06; oGBH=0.51±0.09) and GDF9 (scGBH=0.54±0.05; oGBH=0.53±0.1). Interestingly GBH exposure induced similar effects on ovary independently of exposure routes. No changes were observed in mRNA expression in the remaining genes assayed (ESR1, ESR2, PR, BMP15, BMPR1B and IGF-2). Our results demonstrated that after the neonatal exposure to low doses of GBH, the expression of important genes involved in ovine follicular development is altered independently of administration route. These results combined to previous results provide evidence about effects of GBH effects on reproductive tract and the potential consequences on the adult ovarian function.