title: Neonatal exposure to bisphenol A alters rat uterine implantation-associated gene expression and reduces the number of implantation sites.
abstract: Endocrine disrupters have been associated with reproductive pathologies such as infertility and gynecological tumors. Using a rat model of early postnatal exposure to bisphenol A (BPA), we evaluated the long-term effects on 1) female reproductive performance, 2) uterine homeobox A10 (Hoxa10) and Hoxa10-target gene expression, and 3) ovarian steroid levels and uterine estrogen receptor α and progesterone (P) receptor expression. Newborn female rats received vehicle, BPA.05 (0.05 mg/kg · d), BPA20 (20 mg/kg · d), diethylstilbestrol.2 (0.2 μg/kg · d), or diethylstilbestrol 20 (20 μg/kg · d) on postnatal d 1, 3, 5, and 7. A significant decrease in the number of implantation sites was assessed in the xenoestrogen-exposed females. To address the molecular effects of postnatal xenoestrogen exposure on the pregnant uterus, we evaluated the expression of implantation-associated genes on d 5 of pregnancy (preimplantation uterus). All xenoestrogen-treated rats showed a lower expression of Hoxa10. In the same animals, two Hoxa10-downstream genes were misregulated in the uterus. β(3) Integrin, which is up-regulated by Hoxa10 in controls, was decreased, whereas empty spiracles homolog 2, which is down-regulated by Hoxa10, was increased. Furthermore a clear down-regulation of estrogen receptor α and P receptor expression was detected without changes in estradiol and P serum levels. The early exposure to BPA produced a lower number of implantation sites in association with a defective uterine environment during the preimplantation period. Alterations in the endocrine-regulated Hoxa10 gene pathways (steroid receptors--Hoxa10--β(3) integrin/empty spiracles homolog 2) could explain, at least in part, the BPA effects on the implantation process.
authors.affiliation: Laboratorio de Endocrinología y Tumores Hormonodependientes, School of Biochemistry and Biological Sciences, Casilla de Correo 242, 3000 Santa Fe, Argentina.
authors.forename: Jorgelina
authors.initials: J
authors.lastname: Varayoud
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Ramos
authors.forename: Verónica L
authors.initials: VL
authors.lastname: Bosquiazzo
authors.forename: Melina
authors.initials: M
authors.lastname: Lower
authors.forename: Mónica
authors.initials: M
authors.lastname: Muñoz-de-Toro
authors.forename: Enrique H
authors.initials: EH
authors.lastname: Luque
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001559:Benzhydryl Compounds; D010064:Embryo Implantation / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism; D008297:Male; D010053:Ovary / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014599:Uterus / Q000502:physiology*; D000099260:Empty Spiracles Homeobox Proteins; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D047628:Estrogen Receptor alpha; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D039661:Integrin beta3; D010636:Phenols; D011980:Receptors, Progesterone; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C534680:HOXA10 protein, rat; C006780:bisphenol A; D000098826:Bisphenol A Compounds