Glyphosate-based herbicide worsens alterations induced by cafeteria diet on rat uterus

Author:

Zanardi María Victoria123ORCID,Gastiazoro María Paula12,Rossetti María Florencia14,Doná Florencia1,Lazzarino Gisela Paola14,Zierau Oliver3,Varayoud Jorgelina12,Durando Milena12

Affiliation:

1. Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Santa Fe, Argentina

2. Cátedra de Fisiología Humana, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina

3. Faculty of Biology, Institute of Zoology, Technische Universität Dresden, Dresden, Germany

4. Departamento de Bioquímica Clínica y Cuantitativa, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina

Abstract

Exposure to glyphosate-based herbicides (GBH) and consumption of cafeteria (CAF) diet, which are widespread in Western society, seem to be associated with endometrial hyperplasia (EH). Here, we aimed to evaluate the effects of a subchronic low dose of GBH added to the CAF diet on the rat uterus. Female Wistar rats were fed from postnatal day (PND)21 until PND240 with chow (control) or CAF diet. Since PND140, rats also received GBH (2 mg of glyphosate/kg/day) or water through food, yielding four experimental groups: control, CAF, GBH, and CAF+GBH. On PND240, CAF and CAF+GBH animals showed an increased adiposity index. With respect to the control group, no changes in the serum levels of 17β-estradiol and progesterone were found. However, progesterone levels were higher in the CAF+GBH group than in the CAF and GBH groups. In the uterus, both studied factors alone and in combination induced morphological and molecular changes associated with EH. Furthermore, the addition of GBH provoked an increased thickness of subepithelial stroma in rats fed with the CAF diet. As a consequence of GBH exposure, CAF+GBH rats exhibited an increased density of abnormal gland area, considered preneoplastic lesions, as well as a reduced PTEN and p27 expression, both tumor suppressor molecules that inhibit cell proliferation, with respect to control rats. These results indicate that the addition of GBH exacerbates the CAF effects on uterine lesions and that the PTEN/p27 signaling pathway seems to be involved. Further studies focusing on the interaction between unhealthy diets and environmental chemicals should be encouraged to better understand uterine pathologies.

Publisher

Bioscientifica

Reference66 articles.

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