Table 1.

Molecular and gross phenotypic changes associated with early life EDC exposure

EDC	Exposure	Changes in epigenetic and/or ligand-activated transcription factor regulation; transgenerational effects (when applicable)	Ref.
DES	Perinatal	Increased Ezh2 expression (mRNA and protein) and increased H3K37me3 in F1 mouse mammary gland	[56]
	In utero	Hypermethylation of Hoxa10 gene, increased expression of Dnmt1 and Dnmt3b genes in F1 mouse uterus	[96]
	Postnatal	Increased phospho-EZH2 via ER-activated PI3K/Akt pathway, reduced H3K27me3 in F1 rat uterus; ERα knockout mouse failed activate PI3K/Akt signaling cascade	[110]
Vinclozolin	In utero	Increased spermatogenic cell apoptosis, reduced epididymal sperm counts and sperm mobility in F1–F4 rats, altered DNA methylation in F2 and F3 epididymal sperm	[99]
	In utero	Altered DNA methylation at imprinted genes in F1–F3 mouse sperm	[100]
	In utero	Reduced AR expression, increased NF-κB activation, increased Dnmt3a and Dnmt3b expression in F1 rat prostate; reduced Dnmt1 and Dnmt3l but increased Dnmt3b in F1 rat testis	[111]
	In utero	Altered methylation at 24 DMRs in primordial germ cells and 14 DMRs in prospermatogonia of F3 rat embryos; no assessment of Dnmt levels	[112]
Methoxychlor	In utero	Altered methylation at imprinted genes in F1 and F2 mouse sperm; not significant in F3	[113]
	In utero	37 DMRs in F3 rat sperm; DMR associated genes involved in PI3K signaling system and steroid hormone biosynthesis	[102]
	Perinatal	Hypermethylation in Esr2 promoter, reduced Esr2 expression, increased Dnmt3b expression in F1 rat ovaries	[114]
DDT	Postnatal	Decreased AR expression in testis and upregulation of PXR in F0 male mouse liver	[115]
TCDD	In utero	Altered methylation and expression at imprinted genes in muscle and liver; increased expression of lncRNA Airn in F1 mouse sperm	[116]
	Perinatal	AR expression reduced in F1 rat ventral prostate	[117]
	In utero	50 DMRs in promoter regions of F3 rat sperm, including Jmjd8 and Hdac3 genes	[118]
Tributyltin	In utero	Increase in obesity-related parameters (i.e. increased white adipose tissue, hepatic lipid accumulation) in F1–F3 mice	[119]

Perinatal refers to exposure in utero and after birth