Neonatal exposure to a glyphosate-based herbicide alters the histofunctional differentiation of the ovaries and uterus in lambs

RIVERA, OSCAR; DEMONTE LD; MUÑOZ-DE-TORO, MÓNICA; INGARAMO, PAOLA; REPETTI MR; VARAYOUD J.; INGARAMO, PAOLA; REPETTI MR; VARAYOUD J.; ALARCÓN, RAMIRO; DIOGUARDI, GISELA ; MILESI, MARÍA MERCEDES; LUQUE, ENRIQUE H; ALARCÓN, RAMIRO; DIOGUARDI, GISELA ; MILESI, MARÍA MERCEDES; LUQUE, ENRIQUE H; RIVERA, OSCAR; DEMONTE LD; MUÑOZ-DE-TORO, MÓNICA

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2019 p. 45 - 56

0303-7207

The aim of the present study was to compare the effect of oral and subcutaneousexposure to a glyphosate-based herbicide (GBH) on the female reproductive system, specifically in the ovaries and uterus of prepubertal lambs. To this end, ewe lambs were exposed to a s.c. (n: 5) or an oral (n: 5) environmentally relevant dose of GBH (2 mg/Kg/day) or to vehicle (controls, n: 12), from postnatal day (PND) 1 to PND14.Serum glyphosate and aminomethylphosphonic acid (AMPA) concentrations weremeasured on PND15 and PND45. The ovaries and uterus were obtained and weighedon PND45. Ovarian follicular dynamics and uterine morphological features weredetermined by picrosirius-hematoxylin staining. The proliferation marker Ki67 was evaluated by immunohistochemistry in ovarian and uterine samples. Glyphosate but not AMPA was detected in serum of exposed lambs on PND15, whereas neitherglyphosate nor AMPA were detected on PND45. Controls were negative. GBHexposure did not affect ovarian or uterine weight. However, on PND45, the ovary of GBH-exposed lambs showed altered follicular dynamics, increased proliferation of granulosa and theca cells, and decreased mRNA expression of FSHR and GDF9,whereas their uterus showed decreased cell proliferation but no alterations in the histomorphology or gene expression. In conclusion, GBH exposure altered the ovarian follicular dynamics and gene expression, and the proliferative activity of the ovaries and uterus of ewe lambs. It is noteworthy that all the adverse effects found in the ovaries and uterus of both GBH-exposed groups were similar, independently of the administration route.