Neonatal exposure of ewe lambs to a glyphosate-based herbicide adversely affects ovarian follicular development independently of administration route

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

Mar del Plata, Buenos Aires, Argentina

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

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

Glyphosate-based herbicides (GBH) are widely used around the world. Previous studies suggest that GBH may act as endocrine disruptor. Our hypothesis suggests that low doses of GBH affect ovarian ovine development. Ewe lambs were exposed from postnatal day (PND) 1 to PND14 to sc (n: 13) or orally (n: 5) environmentally relevant doses of GBH (2 mg/Kg/day, EPA reference dose) and controls (n: 13) with saline solution. On PND 45 ovaries were weighted and paraf6n-embedded, sectioned in 4 adjacent 5 µm -serial sections taken 200 µm apart. Follicular dynamic was established by histomorphological features on picrosirious-hematoxilin-stained sections (8 sections/ovary). Follicles of different types and multioocyte follicles were expressed as a percentage. Immunohistochemistry of androgen receptor (AR) and Ki (proliferation marker) were evaluated. Proliferation was measured in granulose (GC) and theca cells (TC) of antral follicles. GBH treatment did not alter ovarian weight, total number of follicles or AR expression. Lambs exposed to GBH showed a reduction of primordial follicles (C=87.9+2.7; scGBH=57.8+3.9; oGBH=62.7+5.4) together with an increase of transitory (C=6.8+1.7; scGBH=36.2+3.3; oGBH=30.7+4.6) and primary (C=1.4+0.2; scGBH=4.4+0.9; oGBH=5.2+1) follicles. In addition, GBH treatment increased the percentage of atretic follicles (C=29.0+3.7; scGBH=44.3+4.0; oGBH=44.3+2.9) and induced higher proliferation of GC (C=26.3+5.5; scGBH=43.3+5.1; oGBH=52.8+11.1) and TC (C=4.9+0.9; scGBH=11.1+1.6; oGBH=28.7+4.8) in antral follicles. Moreover, an increased incidence of multioocyte follicles (C=0.1+0.1; scGBH=1.3+0.4; oGBH=1.1+0.3) was observed. Our results demonstrated that neonatal exposure to low doses of GBH disrupts the ovine follicular development independently of administration route, showing no differences between sc and oral treatment. Further studies with the same GBH protocol will define whether the described effects have consequences in the adult ovarian function.