Neonatal glyphosate based herbicide exposure enhances the sensitivity of the rat uterus to estradiol

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

Congreso; Reunión conjunta de sociedades de Biociencias; 2017

Endometrial adenocarcinoma is considered to be related with a hyperestrogenic state, often associated with endometrial hyperplasia. In a previous work, we demonstrated that neonatal exposure to a glyphosate based herbicide (GBH) alters uterine development in prepubertal rats causing endometrial hyperplasia together with increased cell proliferation. Our goal in the present study was to determine whether exposure to low-dose of a GBH during postnatal development might enhance the sensitivity of the uterus to an estrogenic treatment. Female Wistar pups were injected subcutaneously with saline solution (control, C) or GBH using the reference dose (2 mg/kg/day, EPA) on postnatal days (PND) 1, 3, 5, and 7. At weaning (PND21), female rats were bilaterally ovariectomized and treated with silastic capsules filled with 17β-estradiol (E2, 1mg/ml) until they were two months of age. On PND60, uterine samples were removed and processed for histology and for mRNA extraction to evaluate: i) morphological changes, ii) cell proliferation by Ki67 immunostaining and, iii) the expression of the estrogen receptors alpha (ESR1) and beta (ESR2) using immunohistochemistry and real time PCR. GBH treatment elicited uterine histological abnormalities after E2 stimulation. The luminal and glandular epithelium in three out of seven GBH-exposed animals were markedly hyperplastic. Moreover, the luminal epithelial cells of the GBH group showed a dramatically increase in cell proliferation (C: 16.36 ± 1.10%; GBH: 29.07 ± 3.89%, p