title: Neonatal exposure to low doses of endosulfan induces implantation failure and disrupts uterine functional differentiation at the pre-implantation period in rats.
abstract: We investigated whether neonatal exposure to low doses of endosulfan affects fertility and uterine functional differentiation at pre-implantation in rats. Newborn female rats received the vehicle, 0.2 µg/kg/d of diethylstilbestrol (DES), 6 µg/kg/d of endosulfan (Endo6) or 600 µg/kg/d of endosulfan (Endo600) on postnatal days (PND) 1, 3, 5, and 7. On PND90, the rats were mated to evaluate their reproductive performance on gestational day (GD) 19 and their ovarian steroid serum levels, endometrial proliferation and implantation-associated proteins on GD5. DES and endosulfan decreased the pregnancy rate and the number of implantation sites. On GD5, DES and endosulfan did not change the serum levels of 17β-estradiol (E2) and progesterone (P); the endometrial proliferation decreased, which was associated with silencing of Hoxa10 in the Endo600-treated rats. Both doses of endosulfan increased the progesterone receptor (PR) expression, whereas the higher dose led additionally to an increase in estrogen receptor alpha (ERα). In the Endo600-treated rats, the down-regulation of Hoxa10 was associated with a deregulation of the steroid receptor coregulators. Alterations in endometrial proliferation and the endocrine pathway of Hoxa10/steroid receptors/coregulators might be the mechanism of endosulfan-induced implantation failure.
authors.affiliation: 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.
authors.forename: María M
authors.initials: MM
authors.lastname: Milesi
authors.affiliation: 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.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Alarcón
authors.affiliation: 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.
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Ramos
authors.affiliation: 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.
authors.forename: Mónica
authors.initials: M
authors.lastname: Muñoz-de-Toro
authors.affiliation: 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.
authors.forename: Enrique H
authors.initials: EH
authors.lastname: Luque
authors.affiliation: 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. Electronic address: varayoud@fbcb.unl.edu.ar.
authors.forename: Jorgelina
authors.initials: J
authors.lastname: Varayoud
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000187:drug effects*; D004726:Endosulfan / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D005298:Fertility / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007306:Insecticides / Q000008:administration & dosage* / Q000633:toxicity; D011247:Pregnancy; D018873:Pregnancy Rate; D051381:Rats; D017208:Rats, Wistar; D013256:Steroids / Q000097:blood; D014599:Uterus / Q000187:drug effects* / Q000254:growth & development
chemical_list: D002273:Carcinogens; D007306:Insecticides; D013256:Steroids; D004054:Diethylstilbestrol; D004726:Endosulfan
keywords: Endosulfan; Estrogen receptor alpha; Hoxa10; Implantation; Progesterone receptor; Uterus