Postnatal exposure to endosulfan interferes with the normal development of the male rat mammary gland

ALTAMIRANO GA; DELCONTE MB; GOMEZ AL; MASAT E; ALARCÓN R; BOSQUIAZZO VL; LUQUE EH; MUÑOZ-DE-TORO M; KASS L

Mar del Plata

Congreso; LXI Reunión de la Sociedad Argentina de Investigación Clínica; 2016

Sociedad Argentina de Investigación Clínica

Endosulfan is one ofthe organochlorine pesticides that can act as an estrogen agonist and, it hasbeen shown that stimulates the proliferation of the human mammary tumor cell line MCF-7 in vitro. The male rat mammary gland (MG) is sensitive to endocrine disruptors and,in the present study, our aim was to evaluatewhether postnatal exposure to endosulfan modifies MG development in pre andpostpubertal male rats. From postnatal day 1 (PND1) to PND7, male animals were injectedsubcutaneously every 48 h with: a) corn oil (vehicle, control) or b) 600 ug/kgbody weight of endosulfan. On PND21 and PND60, blood and MG samples werecollected. MG were processed for whole mount (WM) or paraffin embedded. Testosterone(T) serum levels, MG histo-morphology, collagen fibers organization, proliferationindex, and the expression of estrogen (ESR1) and androgen receptor (AR) wereevaluated. On PND21, MG area, perimeter, longitudinal growth and number of terminalend buds (TEBs) were higher in endosulfan-exposed than in control rats. Changesin histological sections such as alveolar development and increased presence oforganized collagen in the stroma parallel those observed in the WM. Also, epithelialESR1 expression was higher in endosulfan-exposed (42.7±1.7%) than in controlrats (33.2±1.7%, p<0.05). On PND60, an increased longitudinal growth andnumber of terminal structures were correlated with a higher proliferation indexin endosulfan-exposed (6.8±0.7%) than in control animals (4.9±0.3%; p<0.05).More developed lobuloalveolar structures in addition to hyperplastic ducts surroundedby dense stroma, rich in collagen fibers, were observed in endosulfan-treatedrats. On the other hand, T levels and AR expression were similar between groups.In conclusion, our results show that the exposure to endosulfan in the firstweek of life interferes with the normal development of the MG and inducespre-malignant lesions in postpubertal male rats.