期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 401, 期 C, 页码 248-259出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2014.11.028
关键词
Endosulfan; Uterus; Implantation; Estrogen receptor alpha; Progesterone receptor; Hoxa10
资金
- CONICET [PIP 112-200801-00218]
- Agencia Nacional de Promocion Cientifica y Tecnologica (ANPCyT) [PICT 2011-1491]
- Universidad Nacional del Litoral (CAI + D) [501 201101 00423 LI]
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 mu g/kg/d of diethylstilbestrol (DES), 6 mu g/kg/d of endosulfan (Endo6) or 600 mu g/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 17 beta-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 (ER alpha). 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. (c) 2014 Elsevier Ireland Ltd. All rights reserved.
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