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Mol Cell Endocrinol. 2019 Feb 15;482:45-56. doi: 10.1016/j.mce.2018.12.007. Epub 2018 Dec 11.

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

Author information

1
Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquímica y Ciencias Biológicas, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional del Litoral, Santa Fe, Argentina.
2
Instituto de Investigación sobre Producción Agropecuaria, Ambiente y Salud (IIPAAs), Facultad de Ciencias Agrarias, Universidad Nacional de Lomas de Zamora, Buenos Aires, Argentina.
3
Programa de Investigación y Análisis de Residuos y Contaminantes Químicos (PRINARC), Facultad de Ingeniería Química, Universidad Nacional del Litoral, Santa Fe, Argentina.
4
Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquímica y Ciencias Biológicas, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional del Litoral, Santa Fe, Argentina. Electronic address: enriquehluque@gmail.com.

Abstract

The aim of the present study was to compare the effect of oral and subcutaneous exposure 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 were measured on PND15 and PND45. The ovaries and uterus were obtained and weighed on PND45. Ovarian follicular dynamics and uterine morphological features were determined 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 neither glyphosate nor AMPA were detected on PND45. Controls were negative for glyphosate and AMPA on PND15 and PND45. GBH exposure 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 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.

KEYWORDS:

Animal production; Environmental contamination; Farm animal; Fertility; Glyphosate

PMID:
30550814
DOI:
10.1016/j.mce.2018.12.007

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