PMID- 30391669
OWN - NLM
STAT- MEDLINE
DCOM- 20190517
LR  - 20231213
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Linking)
VI  - 480
DP  - 2019 Jan 15
TI  - Epigenetic disruption of estrogen receptor alpha is induced by a glyphosate-based 
      herbicide in the preimplantation uterus of rats.
PG  - 133-141
LID - S0303-7207(18)30317-4 [pii]
LID - 10.1016/j.mce.2018.10.022 [doi]
AB  - Previously, we have shown that perinatal exposure to a glyphosate-based herbicide 
      (GBH) induces implantation failures in rats. Estrogen receptor alpha (ERalpha) is 
      critical for successful implantation. ERalpha transcription is under the control of 
      five promoters (E1, OT, O, ON, and OS), which yield different transcripts. Here, 
      we studied whether perinatal exposure to a GBH alters uterine ERalpha gene expression 
      and prompts epigenetic modifications in its regulatory regions during the 
      preimplantation period. Pregnant rats (F0) were orally treated with 350 mg 
      glyphosate/kg bw/day through food from gestational day (GD) 9 until weaning. F1 
      females were bred, and uterine samples were collected on GD5 (preimplantation 
      period). ERalpha mRNA levels and its transcript variants were evaluated by RT-qPCR. 
      Enzyme-specific restriction sites and predicted transcription factors were 
      searched in silico in the ERalpha promoter regions to assess the methylation status 
      using the methylation-sensitive restriction enzymes-PCR technique. 
      Post-translational modifications of histones were studied by the chromatin 
      immunoprecipitation assay. GBH upregulated the expression of total ERalpha mRNA by 
      increasing the abundance of the ERalpha-O transcript variant. In addition, different 
      epigenetic changes were detected in the O promoter. A decrease in DNA methylation 
      was observed in one of the three sites evaluated in the O promoter. Moreover, 
      histone H4 acetylation and histone H3 lysine 9 trimethylation (H3K9me3) were 
      enriched in the O promoter in GBH-exposed rats, whereas H3K27me3 was decreased. 
      All these alterations could account for the increase in ERalpha gene expression. Our 
      findings show that perinatal exposure to a GBH causes long-term epigenetic 
      disruption of the uterine ERalpha gene, which could be associated with the 
      GBH-induced implantation failures.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Lorenz, Virginia
AU  - Lorenz V
AD  - Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquimica y 
      Ciencias Biologicas, Universidad Nacional del Litoral - Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas (CONICET), Santa Fe, Argentina.
FAU - Milesi, Maria M
AU  - Milesi MM
AD  - Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquimica y 
      Ciencias Biologicas, Universidad Nacional del Litoral - Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas (CONICET), Santa Fe, Argentina.
FAU - Schimpf, Marlise Guerrero
AU  - Schimpf MG
AD  - Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquimica y 
      Ciencias Biologicas, Universidad Nacional del Litoral - Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas (CONICET), Santa Fe, Argentina.
FAU - Luque, Enrique H
AU  - Luque EH
AD  - Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquimica y 
      Ciencias Biologicas, Universidad Nacional del Litoral - Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas (CONICET), Santa Fe, Argentina.
FAU - Varayoud, Jorgelina
AU  - Varayoud J
AD  - Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquimica y 
      Ciencias Biologicas, Universidad Nacional del Litoral - Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas (CONICET), Santa Fe, Argentina. Electronic 
      address: varayoud@fbcb.unl.edu.ar.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181102
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Herbicides)
RN  - 0 (Histones)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Computer Simulation
MH  - DNA Methylation/drug effects/genetics
MH  - Embryo Implantation/drug effects/*genetics
MH  - *Epigenesis, Genetic/drug effects
MH  - Estrogen Receptor alpha/*genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation, Developmental/drug effects
MH  - Genome
MH  - Glycine/*analogs & derivatives/toxicity
MH  - Herbicides/*toxicity
MH  - Histones/metabolism
MH  - Promoter Regions, Genetic
MH  - Protein Processing, Post-Translational/drug effects
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats, Wistar
MH  - Transcription Factors/metabolism
MH  - Transcription, Genetic/drug effects
MH  - Uterus/drug effects/*metabolism
MH  - Glyphosate
OTO - NOTNLM
OT  - Epigenetic modifications
OT  - Estrogen receptor alpha
OT  - Glyphosate-based herbicide
OT  - Preimplantation period
OT  - Uterus
EDAT- 2018/11/06 06:00
MHDA- 2019/05/18 06:00
CRDT- 2018/11/05 06:00
PHST- 2018/08/10 00:00 [received]
PHST- 2018/10/29 00:00 [revised]
PHST- 2018/10/31 00:00 [accepted]
PHST- 2018/11/06 06:00 [pubmed]
PHST- 2019/05/18 06:00 [medline]
PHST- 2018/11/05 06:00 [entrez]
AID - S0303-7207(18)30317-4 [pii]
AID - 10.1016/j.mce.2018.10.022 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2019 Jan 15;480:133-141. doi: 10.1016/j.mce.2018.10.022. 
      Epub 2018 Nov 2.