Postnatal endosulfan exposure alters endocrine signalling and endometrial proliferation in the rat

VARAYOUD JORGELINA; MILESI MARÍA M; ALARCÓN RAMIRO; RIVERA OSCAR E; MUÑOZ-DE-TORO MÓNICA; LUQUE ENRIQUE H

Mendoza

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2012

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

Previously we showed that an early postnatal exposure to the pesticide endosulfan reduces fertility in a rat model. Here, we evaluated the molecular changes in the subepithelial stroma of the endometrium associated with subfertility. Newborn female rats received vehicle or endosulfan (600 ug/kg/day) on postnatal day 1, 3, 5, and 7. To address the molecular effects of endosulfan exposure on the pregnant uterus, we evaluated the implantation-associated protein expression and endometrial proliferation on day 5 of pregnancy (preimplantation uterus) using immunohistochemistry. The animals received 60 mg/kg of bromodeoxiuridine (BrdU) and uterine tissues were harvested 2 hour after. The endosulfan-treated rats showed an impaired proliferation of subepithelial stromal cells associated with a silencing of Hoxa10 protein. This reduction was accompanied by an increase of the co-repressor SMRT (silencing mediator for retinoic acid and thyroid hormone receptor). Furthermore, an up-regulation of estrogen receptor alpha and progesterone receptor expression was observed. The subfertility detected after postnatal exposure to endosulfan is associated with a modified uterine environment during the preimplantation period. Alterations in the endocrine signalling and endometrial proliferation could explain, at least in part, the effects of early exposure to endosulfan on the implantation process.