Identification of hot spots of DNA methylation in the adult male adrenal in response to in utero exposure to the ubiquitous endocrine disruptor plasticizer di-(2-ethylhexyl) phthalate.

Exposure to environmental toxicants during fetal development alters gene
expression and promotes disease later in life. Di-(2-ethylhexyl)
phthalate (DEHP) is a plasticizer widely used for the manufacturing of
consumer products. Exposure to DEHP has been associated with obesity,
asthma, and low testosterone levels. In utero exposure of pregnant dams
to DEHP from gestational day 14 until birth resulted in reduced levels
of serum testosterone and aldosterone in the adult male offspring. Since
DEHP is rapidly cleared from the body, the effects observed in the
adult are likely epigenetic in origin. Under the same experimental
conditions, we used reduced-representation bisulfite sequencing to
assess changes in DNA methylation. We identified hot spots of DNA
methylation changes primarily within CpG islands followed by shelf
regions of the genome known to control regional gene expression. We also
identified epigenomic areas responsive to exposure to environmental
levels of DEHP and found the chromosomal region that houses genes
controlling immune responsiveness to be a primary target of DEHP. These
data suggest that DEHP phthalate exposure early in life induces
epigenetic changes that may be linked to altered gene expression and
function in the adult.