Table 1.
Animal studies providing an epigenetic link between prenatal environmental exposure and neurobehavioral outcomes.
| Study | Species (Strain) | Stress Paradigm | Offspring Sex and Age | Brain Area | Analysis | Gene (Epigenetic Changes) | Epigenetic Regulators | Neurobehavioral Outcome | Sex Specificity |
|---|---|---|---|---|---|---|---|---|---|
| Basil et al., 2014 [49] | Mouse (C57BL/6N) | Maternal immune activation (GD17) | Males and females, PD42 | Hy | Sequenom EpiTYPER assay | Mecp2, LINE1 | - | - | Males and females; more profound changes in females |
| DiNieri et al., 2011 [50] | Rat (Long Evans) | THC rat model (GD5-PD2) | Males, PD62 | NAc | ChIP (H3K9me2, H3K4me3, RNA polymerase II) | Drd2 | - | Increased sensitivity to opiate reward; Drd2 transcriptional changes | - |
| Dong et al., 2015 [51] | Mouse (Swiss albino ND4) | Restrain stress (GD7-GD21) | Males, PD75 | FC, Hy | MeDIP, hMeDIP, ChIP | Bdnf | Dnmt1, Tet1 | Hyperactivity; Impaired social interaction; Bdnf transcriptional changes | - |
| Kaminen-Ahola et al., 2010 [52] | Mouse (C57BL/6J Agoutivy) | Ethanol exposure (GD0.5-GD8.5) | Males and females, PD28–30 | FB | Bisulfite Sequencing, Gene Expression Arrays | IAPs | - | Fetal alcohol syndrome-like features | - |
| Kundakovic et al., 2013 [53] | Mouse (BALB/c) | BPA exposure (GD0-GD19) | Males and females, PD30–70 | PFC, Hi, Hy | Bisulfite Pyrosequencing | Esr1 | Dnmt1, Dnmt3a | Disrupted exploratory, social and anxiety-like behavior; transcriptional changes in Esr1, Esr2 and Esrrg | Sex specific changes |
| Kundakovic et al., 2015 [48] | Mouse (BALB/c) | BPA exposure (GD0-GD19) | Males and females, PD28 and PD60 | Hi | Bisulfite Pyrosequencing | Bdnf IV, Bdnf IX, Grin2b | Dnmt1, Gadd45b | Disrupted exploration of a novel object; Bdnf and Grin2b transcriptional changes | Changes were observed in males |
| Labouesse et al., 2015 [54] | Mouse (C57BL/6N) | Maternal immune activation (GD17) | PD80–100 | mPFC | MeDIP, hMeDIP, ChIP (MeCP2) | Gad1, Gad2 | MeCP2 | Impaired working memory and social interaction deficits; Gad1 and Gad2 transcriptional changes | - |
| Mueller and Bale, 2008 [55] | Mouse (C57BL/6N:129) | Chronic, variable stress during early, mid and late gestation | Males and females, 6–16 weeks | Hi, Am | Bisulfite Pyrosequencing | Crf, Nr3c1 | - | Maladaptive behavioral stress-responsivity, anhedonia, and an increased sensitivity to SSRI treatment in males | Sex specific changes |
| Matrisciano et al., 2013 [56] | Mouse (Swiss albino ND4) | Restrain stress (GD7-GD21) | Males, PD60 | PFC, Hi | MeDIP, hMeDIP, ChIP (Dnmt1, MeCP2) | Reelin, Gad1 | Dnmt 1, Dnmt 3a | Hyperactivity; Impaired social interaction, prepulse inhibition, and fear conditioning; Reelin and Gad1 transcriptional changes | |
| Novikova et al., 2008 [57] | Mouse (CD1) | Cocaine exposure (GD8-GD19) | Males, PD3 and PD30 | Hi | Bisulfite sequencing, MeDIP/CGI array | Genome-wide | Dnmt1, Dnmt 3a | Transcriptional changes in Gpr73, Plk2, Prpn5, Mapk1, Impa1, Pyrk3, Gata4, Mtap6, Gtf3c1, Coq7 | - |
| Onishchenko et al., 2008 [58] | Mouse (C57BL/6/Bkl) | MeHg exposure (GD7-PD7) | Males, 9 weeks | DG | ChIP (H3ac, H3K27me3), Ms-SNuPE | Bdnf | Depresion like behavior; transcriptional changes in Bdnf | - | |
| Richetto et al., 2017 [59] | Mouse (C57BL6/N) | Maternal immune activation (GD9 and GD17) | Males, PD100 | mPFC | SureSelectXT capture sequencing assay and EpiTYPER | Genome wide (Dlx1, Lhx5, Lhx8, Wnt3, Wnt8a, Wnt7b, Efnb3, Mid1, Nlgn1, Nrxn2, Nf2, etc.) | - | Impaired sensorimotor gating, social interaction and spatial memory; transcriptional changes in Dlx1, Wnt3, Mid1, Nlgn1, Nf2 | - |
| Schraut et al., 2014 [60] | Mouse (C57BL6/J, 5-Htt +/+ and 5-Htt +/−) | Restrain stress (GD13-GD17) | Females, PD95 | Hi | MeDIP-on-Chip | Genome wide | - | Anxiety-related behavior; Mdb transcriptional changes | - |
| St-Cyr S and McGowan, 2015 [61] | Mouse (C57BL/6N) | Exposure to predator odor (GD11-GD18) | Females and males, PD90 | Hi, Am | Bisulfite Pyrosequencing | Bdnf | - | Increased avoidance and decreased predator-odor associated activity; Bdnf and Crhr1 transcriptional changes | Males and females, but females showed a greater increase in CORT level |
| Zheng et al., 2016 [62] | Mouse (Kunming) | Restrain stress (GD5-delivery) | Males, PD40 | Hi | MeDIP,ChiP (H3K14ac) | Bdnf | Dnmt1, Hdac1, Hdac2, | Depressive-like and anxiety-like behaviors, Bdnf transcriptional changes | - |
Abbreviation List: GD—gestational day, PD—postnatal day, THC—delta-9-tetrahydrocannabinol, BPA—Bisphenol A, MeHg—methylmercury, Hy—hypothalamus, NAc—nucleus accumbens, FC—frontal cortex, FB—forebrain, PFC—prefrontal cortex, mPFC—medial prefrontal cortex, Hi—hippocampus, Am—amygdala, DG—dentate gyrus, ChIP—Chromatin Immunoprecipitation, MeDIP—Methylated DNA immunoprecipitation, hMeDIP—Hydroxymethylated DNA Immunoprecipitation, MeDIP-CGI-arrays—methylated DNA immunoprecipitation coupled with CpG island microarrays, Ms-SNuPE—Methylation-sensitive single-nucleotide primer extension, LINE1—long interspersed element, IAPs—intracisternal A-particles.