Environmental compounds including fungicides, plastics, pesticides, dioxin and hydrocarbons can promote the epigenetic transgenerational inheritance of adult-onset disease in future generation progeny following ancestral exposure during the critical period of fetal gonadal sex determination. This study examined the actions of the pesticide methoxychlor to promote the epigenetic transgenerational inheritance of adult-onset disease and associated differential DNA methylation regions (i.e. epimutations) in sperm. Gestating F0 generation female rats were transiently exposed to methoxychlor during fetal gonadal development (gestation days 8 to 14) and then adult-onset disease was evaluated in adult F1 and F3 (great-grand offspring) generation progeny for control (vehicle exposed) and methoxychlor lineage offspring. There were increases in the incidence of kidney disease, ovary disease, and obesity in the methoxychlor lineage animals. In females and males the incidence of disease increased in both the F1 and the F3 generations and the incidence of multiple disease increased in the F3 generation. There was increased disease incidence in F4 generation reverse outcross (female) offspring indicating disease transmission was primarily transmitted through the female germline. Analysis of the F3 generation sperm epigenome of the methoxychlor lineage males identified differentially DNA methylated regions (DMR) termed epimutations in a genome-wide gene promoters analysis. These epimutations were found to be methoxychlor exposure specific in comparison with other exposure specific sperm epimutation signatures. Observations indicate that the pesticide methoxychlor has the potential to promote the epigenetic transgenerational inheritance of disease and the sperm epimutations appear to provide exposure specific epigenetic biomarkers for transgenerational disease and ancestral environmental exposures.
Pharmacology, Toxicology and Pharmaceutical Science
7
3%
Other
46
22%
Unknown
62
30%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 173. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 June 2026.
All research outputs
#295,209
of 34,410,798 outputs
Outputs from PLOS ONE
#4,010
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Outputs of similar age
#2,023
of 270,029 outputs
Outputs of similar age from PLOS ONE
#80
of 5,085 outputs
Altmetric has tracked 34,410,798 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 224,657 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 17.2. This one has done particularly well, scoring higher than 98% of its peers.
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We're also able to compare this research output to 5,085 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 98% of its contemporaries.
