PMID- 36035158
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221110
IS  - 1664-8021 (Print)
IS  - 1664-8021 (Electronic)
IS  - 1664-8021 (Linking)
VI  - 13
DP  - 2022
TI  - Elevated exposures to persistent endocrine disrupting compounds impact the sperm 
      methylome in regions associated with autism spectrum disorder.
PG  - 929471
LID - 10.3389/fgene.2022.929471 [doi]
LID - 929471
AB  - Environmental exposures to endocrine disrupting compounds (EDCs) such as the 
      organochlorines have been linked with various diseases including 
      neurodevelopmental disorders. Autism spectrum disorder (ASD) is a highly complex 
      neurodevelopmental disorder that is considered strongly genetic in origin due to 
      its high heritability. However, the rapidly rising prevalence of ASD suggests 
      that environmental factors may also influence risk for ASD. In the present study, 
      whole genome bisulfite sequencing was used to identify genome-wide differentially 
      methylated regions (DMRs) in a total of 52 sperm samples from a cohort of men 
      from the Faroe Islands (Denmark) who were equally divided into high and low 
      exposure groups based on their serum levels of the long-lived organochlorine 
      1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), a primary breakdown product 
      of the now banned insecticide dichlorodiphenyltrichloroethane (DDT). Aside from 
      being considered a genetic isolate, inhabitants of the Faroe Islands have a 
      native diet that potentially exposes them to a wide range of seafood 
      neurotoxicants in the form of persistent organic pollutants (POPs). The DMRs were 
      mapped to the human genome using Bismark, a 3-letter aligner used for methyl-seq 
      analyses. Gene ontology, functional, and pathway analyses of the DMR-associated 
      genes showed significant enrichment for genes involved in neurological functions 
      and neurodevelopmental processes frequently impacted by ASD. Notably, these genes 
      also significantly overlap with autism risk genes as well as those previously 
      identified in sperm from fathers of children with ASD in comparison to that of 
      fathers of neurotypical children. These results collectively suggest a possible 
      mechanism involving altered methylation of a significant number of neurologically 
      relevant ASD risk genes for introducing epigenetic changes associated with 
      environmental exposures into the sperm methylome. Such changes may provide the 
      potential for transgenerational inheritance of ASD as well as other disorders.
CI  - Copyright (c) 2022 Maggio, Shu, Laufer, Bi, Lai, LaSalle and Hu.
FAU - Maggio, Angela G
AU  - Maggio AG
AD  - Department of Biochemistry and Molecular Medicine, The George Washington 
      University School of Medicine and Health Sciences, Washington, DC, United States.
FAU - Shu, Henry T
AU  - Shu HT
AD  - Department of Biochemistry and Molecular Medicine, The George Washington 
      University School of Medicine and Health Sciences, Washington, DC, United States.
AD  - The Johns Hopkins University, School of Medicine, Baltimore, MD, United States.
FAU - Laufer, Benjamin I
AU  - Laufer BI
AD  - Genome Center, Perinatal Origins of Disparities Center, Environmental Health 
      Sciences Center, Medical Microbiology and Immunology, MIND Institute, UC Davis 
      School of Medicine, Davis, CA, United States.
FAU - Bi, Chongfeng
AU  - Bi C
AD  - Department of Biochemistry and Molecular Medicine, The George Washington 
      University School of Medicine and Health Sciences, Washington, DC, United States.
FAU - Lai, Yinglei
AU  - Lai Y
AD  - Department of Statistics, The George Washington University, Washington, DC, 
      United States.
FAU - LaSalle, Janine M
AU  - LaSalle JM
AD  - Genome Center, Perinatal Origins of Disparities Center, Environmental Health 
      Sciences Center, Medical Microbiology and Immunology, MIND Institute, UC Davis 
      School of Medicine, Davis, CA, United States.
FAU - Hu, Valerie W
AU  - Hu VW
AD  - Department of Biochemistry and Molecular Medicine, The George Washington 
      University School of Medicine and Health Sciences, Washington, DC, United States.
LA  - eng
GR  - P30 ES023513/ES/NIEHS NIH HHS/United States
PT  - Journal Article
DEP - 20220811
PL  - Switzerland
TA  - Front Genet
JT  - Frontiers in genetics
JID - 101560621
PMC - PMC9403863
OTO - NOTNLM
OT  - DNA methylation
OT  - Faroe Islands
OT  - autism
OT  - endocrine disrupting compounds
OT  - sperm
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/08/30 06:00
MHDA- 2022/08/30 06:01
PMCR- 2022/08/11
CRDT- 2022/08/29 05:19
PHST- 2022/04/26 00:00 [received]
PHST- 2022/07/11 00:00 [accepted]
PHST- 2022/08/29 05:19 [entrez]
PHST- 2022/08/30 06:00 [pubmed]
PHST- 2022/08/30 06:01 [medline]
PHST- 2022/08/11 00:00 [pmc-release]
AID - 929471 [pii]
AID - 10.3389/fgene.2022.929471 [doi]
PST - epublish
SO  - Front Genet. 2022 Aug 11;13:929471. doi: 10.3389/fgene.2022.929471. eCollection 
      2022.