PMID- 35114330
OWN - NLM
STAT- MEDLINE
DCOM- 20220405
LR  - 20220613
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Linking)
VI  - 547
DP  - 2022 May 1
TI  - Aberrant Hoxa10 gene methylation as a mechanism for endosulfan-induced 
      implantation failures in rats.
PG  - 111576
LID - S0303-7207(22)00023-5 [pii]
LID - 10.1016/j.mce.2022.111576 [doi]
AB  - DNA methylation is a well-established epigenetic mechanism controlling gene 
      expression. Environmental chemicals, such as pesticides have been shown to alter 
      DNA methylation. We have previously shown that the insecticide endosulfan impairs 
      female fertility in rats by increasing the rate of preimplantation embryo losses. 
      In this study, we evaluated whether early postnatal exposure to endosulfan 
      affects long-term transcriptional regulation of Homeobox A10 (Hoxa10) gene, which 
      is a key marker of endometrial receptivity. Female rats were neonatally exposed 
      to 6 or 600 mug/kg/day (ENDO6 and ENDO600, respectively) of endosulfan and uterine 
      samples collected on gestational day (GD) 5. Hoxa10 protein and mRNA levels were 
      assessed by immunohistochemistry and quantitative real-time PCR (qRT-PCR), 
      respectively. In silico analysis of enzyme-specific restriction sites and 
      predicted transcription factors were performed to investigate the methylation 
      status of the regulatory regions of Hoxa10 gene by methylation-sensitive 
      restriction enzymes-PCR technique. The expression of the DNA methyltransferases 
      (Dnmts) was also evaluated. ENDO600 showed a decreased uterine Hoxa10 expression 
      at protein and transcript level, while ENDO6 decreased only the level of 
      transcripts, during the receptive stage. In addition, endosulfan increased levels 
      of Dnmt3a and Dnmt3b. Dysregulation of DNA methylation patterns of Hoxa10 
      regulatory regions was detected in ENDO6- and ENDO600-treated rats. All these 
      results suggest that aberrant DNA methylation in Hoxa10 gene could be an 
      underlining mechanism contributing to explain endosulfan-induced preimplantation 
      losses.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Milesi, Maria Mercedes
AU  - Milesi MM
AD  - Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquimica y 
      Ciencias Biologicas, Universidad Nacional del Litoral (UNL) - Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas (CONICET), Santa Fe, Argentina; Catedra de 
      Fisiologia Humana, Facultad de Bioquimica y Ciencias Biologicas, Universidad 
      Nacional del Litoral, Santa Fe, Argentina. Electronic address: 
      mmilesi@fbcb.unl.edu.ar.
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 (UNL) - 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 (UNL) - Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas (CONICET), Santa Fe, Argentina; Catedra de 
      Fisiologia Humana, Facultad de Bioquimica y Ciencias Biologicas, Universidad 
      Nacional del Litoral, Santa Fe, Argentina.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220131
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Homeobox A10 Proteins)
RN  - 0 (Homeodomain Proteins)
RN  - OKA6A6ZD4K (Endosulfan)
SB  - IM
MH  - Animals
MH  - DNA Methylation/genetics
MH  - *Embryo Implantation/genetics
MH  - Endometrium/metabolism
MH  - *Endosulfan/toxicity
MH  - Female
MH  - Homeobox A10 Proteins
MH  - Homeodomain Proteins/genetics/metabolism
MH  - Rats
MH  - Uterus/metabolism
OTO - NOTNLM
OT  - Aberrant DNA methylation
OT  - Endosulfan
OT  - Hoxa10
OT  - Implantation
OT  - Uterus
EDAT- 2022/02/04 06:00
MHDA- 2022/04/06 06:00
CRDT- 2022/02/03 20:13
PHST- 2021/09/23 00:00 [received]
PHST- 2022/01/24 00:00 [revised]
PHST- 2022/01/25 00:00 [accepted]
PHST- 2022/02/04 06:00 [pubmed]
PHST- 2022/04/06 06:00 [medline]
PHST- 2022/02/03 20:13 [entrez]
AID - S0303-7207(22)00023-5 [pii]
AID - 10.1016/j.mce.2022.111576 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2022 May 1;547:111576. doi: 10.1016/j.mce.2022.111576. Epub 
      2022 Jan 31.