title: Pesticide chlorpyrifos acts as an endocrine disruptor in adult rats causing changes in mammary gland and hormonal balance.
abstract: Endocrine disruptors (EDs) are compounds that interfere with hormone regulation and influence mammary carcinogenesis. We have previously demonstrated that the pesticide chlorpyrifos (CPF) acts as an ED in vitro, since it induces human breast cancer cells proliferation through estrogen receptor alpha (ERα) pathway. In this work, we studied the effects of CPF at environmental doses (0.01 and 1mg/kg/day) on mammary gland, steroid hormone receptors expression and serum steroid hormone levels. It was carried out using female Sprague-Dawley 40-days-old rats exposed to the pesticide during 100 days. We observed a proliferating ductal network with a higher number of ducts and alveolar structures. We also found an increased number of benign breast diseases, such as hyperplasia and adenosis. CPF enhanced progesterone receptor (PgR) along with the proliferating cell nuclear antigen (PCNA) in epithelial ductal cells. On the other hand, the pesticide reduced the expression of co-repressors of estrogen receptor activity REA and SMRT and it decreased serum estradiol (E2), progesterone (Pg) and luteinizing hormone (LH) levels. Finally, we found a persistent decrease in LH levels among ovariectomized rats exposed to CPF. Therefore, CPF alters the endocrine balance acting as an ED in vivo. These findings warn about the harmful effects that CPF exerts on mammary gland, suggesting that this compound may act as a risk factor for breast cancer.
authors.affiliation: Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
authors.forename: Clara
authors.initials: C
authors.lastname: Ventura
authors.affiliation: Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
authors.forename: María Rosa Ramos
authors.initials: MR
authors.lastname: Nieto
authors.affiliation: Laboratorio de Neuroendocrinología, Instituto de Biología y Medicina Experimental (IByME), CONICET, Argentina.
authors.forename: Nadia
authors.initials: N
authors.lastname: Bourguignon
authors.affiliation: Laboratorio de Neuroendocrinología, Instituto de Biología y Medicina Experimental (IByME), CONICET, Argentina.
authors.forename: Victoria
authors.initials: V
authors.lastname: Lux-Lantos
authors.affiliation: Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Argentina.
authors.forename: Horacio
authors.initials: H
authors.lastname: Rodriguez
authors.affiliation: Instituto de Investigaciones Cardiológicas, CONICET, Argentina.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Cao
authors.affiliation: Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
authors.forename: Andrea
authors.initials: A
authors.lastname: Randi
authors.affiliation: Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cocca
authors.affiliation: Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina. Electronic address: mariel.nu.grand@gmail.com.
authors.forename: Mariel
authors.initials: M
authors.lastname: Núñez
mesh_terms: D000818:Animals; D004390:Chlorpyrifos / Q000009:adverse effects*; D052244:Endocrine Disruptors / Q000009:adverse effects*; D004785:Environmental Pollutants / Q000009:adverse effects*; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000032:analysis; D005260:Female; D007986:Luteinizing Hormone / Q000097:blood; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000473:pathology*; D010575:Pesticides / Q000009:adverse effects*; D011374:Progesterone / Q000032:analysis / Q000097:blood; D000091402:Prohibitins; D051381:Rats; D017207:Rats, Sprague-Dawley; D011980:Receptors, Progesterone / Q000032:analysis
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D047628:Estrogen Receptor alpha; C000717331:PHB2 protein, human; D010575:Pesticides; D000091402:Prohibitins; D011980:Receptors, Progesterone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D004390:Chlorpyrifos
keywords: Breast; Chlorpyrifos; Endocrine; Hyperplasia; Pesticide; Proliferation