Glyphosate-based herbicide enhances the uterine sensitivity to estradiol in rats

GUERRERO SCHIMPF M; MILESI MM; LUQUE EH; VARAYOUD J

JOURNAL OF ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2018 vol. 239

0022-0795

In a previous work, we detected that postnatal exposure to a glyphosate-basedherbicide (GBH) alters uterine development in prepubertal rats causing endometrialhyperplasia and increasing cell proliferation. Our goal was to determine whetherexposure to low dose of a GBH during postnatal development might enhancethe sensitivity of the uterus to an estrogenic treatment. Female Wistar pups weresubcutaneously injected with saline solution (control) or GBH using the reference dose(2 mg/kg/day, EPA) on postnatal days (PND) 1, 3, 5 and 7. At weaning (PND21), femalerats were bilaterally ovariectomized and treated with silastic capsules containing17â-estradiol (E2, 1 mg/mL) until they were 2 months of age. On PND60, uterine sampleswere removed and processed for histology, immunohistochemistry and mRNA extractionto evaluate: (i) uterine morphology, (ii) uterine cell proliferation by the detection ofKi67, (iii) the expression of the estrogen receptors alpha (ESR1) and beta (ESR2) and (iv)the expression of WNT7A and â-catenin. GBH-exposed animals showed increased luminalepithelial height and stromal nuclei density. The luminal and glandular epithelium weremarkedly hyperplastic in 43% of GBH-exposed animals. GBH exposure caused an increasein E2-induced cell proliferation in association with an induction of both ESR1 and ESR2.GBH treatment decreased membranous and cytoplasmic expression of â-catenin inluminal and glandular epithelial cells and increased WNT7A expression in the luminalepithelium. These results suggest that early postnatal exposure to a GBH enhances thesensitivity of the rat uterus to estradiol and induces histomorphological and molecularchanges associated with uterine hyperplasia.