Table 1.
Summary of recent publications focusing on various environmental exposures in relation to placental DNA methylation.
| 1st author, year | Study cohort & size | Exposure | Assay | Direction of effect on DNAme |
|---|---|---|---|---|
| Air Pollution Studies | ||||
| Janssen et. al, 2013 [32] | ENVIRONAGE (n = 240) | PM2.5 | Bisulfite sequencing | ↓ global DNAme (1st trimester, whole pregnancy, implantation) |
| Saenen et. al, 2017 [34] | ENVIRONAGE (n = 361) | PM2.5 | Bisulfite sequencing | ↓ LEP (2nd trimester) |
| Nawrot et. al, 2018 [35] | ENVIRONAGE (n = 407) | PM2.5 | Bisulfite sequencing | ↑ NPAS2, CRY1, PER2, PER3 (3rd trimester) ↓ PER1, CLOCK (3rd trimester) |
| Neven et. al, 2018 [36] | ENVIRONAGE (n = 463) | PM2.5, black carbon, NO2 | Bisulfite sequencing | ↑ APEX1, OGG1, ERCC4, p53 (PM2.5) ↓ DAPK1 (PM2.5) ↑ APEX1, ERCC4 (black carbon) |
| Zhao et. al, 2021 [37] | Shanghai MCPC (n = 287) | PM2.5 | Infinium 450K | ↑ IGF2, ↓ BID (2nd & 3rd trimester, whole pregnancy) ↑ FOX3N (2nd trimester) |
| Maghbooli et. al, 2018 [8] | • Prenatal care clinics in Tehran, Iran (n = 92) ○ Polluted = 48 ○ Non-polluted = 44 |
PM2.5, PM10 | HPLC | ↑ global DNAme (PM2.5 & PM10, 1st trimester) ↑ global DNAme (PM2.5, 3rd trimester, polluted) |
| Yang et. al, 2020 [41] | COCOA (n = 1,180) Grouped analysis: ○ n = 6 for each group (8 groups) ■ High/low exposure groups, high/low CB VD within those, AD within those |
PM2.5 | Infinium 450K | ↓ AHRR, DPP10, HLA-DRB1 (high PM2.5, low CB VD, and AD group) |
| Abraham et. al, 2018 [43] | EDEN (n = 668) | NO2, PM10 | Infinium 450K | ↓ ADORA2B (NO2, 1st & 2nd trimester, whole pregnancy) ↑ PXT1, KCTD20 (NO2, 2nd trimester & whole pregnancy) ↓ TUBGCP, ↑ TGM6, ADCK5 (PM10, month before birth) ↓ LINE-1, Alu (PM10, 1st trimester) |
| Ladd-Acosta et. al, 2019 [48] | EARLI (n = 133) | NO2, O3 | Infinium 450K | ↓ All probes, CpG islands (NO2) ↑ shores, islands, ↓ shelves (O3) ↓ ZNF442, PTPRH, SLC25A44, F11R (NO2), STK38 (O3) |
| Maternal Smoking Studies | ||||
| Janssen et. al, 2017 [52] | • ENVIRONAGE (n = 382) ○ Smokers (n = 62) ○ Past-smokers (n = 65) ○ Non-smokers (n = 255) |
Cigarette smoke | Bisulfite sequencing | ↑ MT-RNR1 ↓ CYP1A1 |
| Fa et. al, 2017 [54] | • Women seeking legal abortions in Denmark (n = 39) ○ Smoking-exposed (n = 17) |
Cigarette smoke | Bisulfite sequencing | ↑ AHRR |
| Vos et. al, 2021 [55] | • ENVIRONAGE (n = 60) ○ Smokers (n = 20) |
Cigarette smoke | Bisulfite sequencing | ↑ D-loop |
| Cardenas et. al, 2019 [58] | • Gen3G (n = 441) ○ Smokers (n = 38) ○ Non-smokers (n = 403) |
Cigarette smoke | Infinium 450K | ↑ MDS2, PBX1, CYP1A2, VPBRP, CD28, CDK6 ↓ WBP1L |
| Shorey-Kendrick et. al, 2021 [59] | • VCSIP (n = 96) ○ Smokers (n = 72) ■ VCS (n = 37) ■ Placeb ○ (n = 35) ○ Non-smokers (n = 24) |
Cigarette smoke | Infinium 450K | ↑ DIP2C, APOH/PRKCA (VCS) |
| Van Otterdijk et. al, 2017 [60] | • HEBC (n = 120) ○ Smoked during entire pregnancy (n = 27) ○ Quit smoking while pregnant (n = 32) ○ Non-smokers (n = 61) |
Cigarette smoke | Bisulfite sequencing | ↓ AHRR, CYP1A1 (smoked throughout pregnancy) ↓ GFI1 (quit while pregnant) |
| Rousseaux et. al, 2020 [61] | • EDEN (n = 568) ○ Current smokers (n = 117) ○ Former smokers (n = 70) ○ Non-smokers (n = 381) |
Cigarette smoke | Infinium 450K | ↓ LINE-1, ↑ DMRs (current smokers) |
| Everson et. al, 2021 [63] | • PACE (n = 1,700) ○ Any MSDP (n = 344) ○ Sustained MSDP (n = 163) ○ No MSDP (n = 1,193) |
Cigarette smoke | Infinium 450K | ↓ CpG DNAme (Any/sustained MSDP) |
| Chemical Studies | ||||
| Song et. al, 2021 [64] | • S-MBCS (n = 146) ○ Low BPA (n = 108) ○ High BPA (n = 38) |
BPA | Infinium 450K | ↑ CpG DNAme, HLA-DRB6 (high BPA) |
| Jedynak et. al, 2021 [67] | EDEN (n = 202) | Phenols | Infinium 450K | ↑ DMPs, DMRs |
| Kim et. al, 2018 [70] | CHECK (n = 109) | POPs | Bisulfite sequencing | ↓ LINE-1, H19, ↑ IGF2 |
| Zhao et. al, 2019 [73] | • Wenzhou Birth Cohort (n = 249) ○ FGR cases (n = 124) ○ Controls (n = 125) |
PBDEs | Bisulfite sequencing | ↓ IGF2, ↑ HSD11B2 |
| Trace M etal Studies | ||||
| Appleton et. al, 2017 [77] | RICHS (n = 222) | As, Cd, Pb, Mn, Hg, Zn | Bisulfite sequencing | ↑ NR3C1 (higher As, Cd, Pb, Mn, Hg, lower Zn) |
| Everson et. al, 2018 [82] | • RICHS (n = 141) • NHBCS (n = 343) |
Cd | Infinium 450K | ↑ CpG DNAme |
| Tian et. al, 2020 [83] | • RICHS (n = 141) • NHBCS (n = 343) |
Se | Infinium 450K | ↑ GFI1, CAPN9, SKIDA1, ↓ ZNF496, TBC1D5 |
| Kennedy et. al, 2020 [84] | • RICHS (n = 141) • NHBCS (n = 306) |
Cu | Infinium 450K | ↓ Enhancers, active TSS |
| Socioeconomic Adversity Studies | ||||
| Santos et. al, 2019 [86] | ELGAN (n = 426) | SES | Infinium 450K | ↑ ↓ DMPs |
| Appleton et. al, 2013 [87] | RICHS (n = 444) | SES | Bisulfite sequencing | ↓ HSD11B2 |
| CD Studies | ||||
| Clarkson-Townsend et. al, 2019 [88] | • RICHS (n = 237) ○ Night shift (n = 53) ○ No night shift (n = 184) |
CD | Infinium 450K | ↓ DMPs, NAV1, MXRA8, GABRG1, PRDM16, WNT5A, FOXG1 (night shift) ↑ TDO2, ADAMTSL3, DLX2, SERPINA1 |
Abbreviations: ENVIRONAGE = Environmental Influence on Early Aging; PM2.5 = particulate matter ≤ 2.5 μm; DNAme = DNA methylation; NO2 = nitrogen dioxide; Shanghai MCPC = Shanghai Maternal-Child Pairs Cohort; PM10 = particulate matter ≤ 10 μm; HPLC = high performance liquid chromatography; COCOA = Cohort for Childhood Origin of Asthma and Allergic Diseases; CB = cord blood; VD = vitamin D; AD = atopic dermatitis; EARLI = Early Autism Risk Longitudinal Investigation; O3 = ozone; CpG shores = CpG probe ± 2 kb from CpG island; CpG shelves = CpG probe ± 2-4 kb from island; D-loop = displacement loop; Gen3G = Genetics of Glucose regulation in Gestation and Growth; VCSIP = Vitamin C to decrease the effects of smoking in pregnancy on infant lung function; VCS = vitamin C supplement; HEBC = Harvard Epigenetic Birth Cohort; DMRs = differentially methylated regions; PACE = Pregnancy and Childhood Epigenetics; MSDP = maternal smoking during pregnancy; S-MBCS = Shanghai-Minhang Birth Cohort Study; BPA = bisphenol A; DMPs = differentially methylated probes; CHECK = Children’s Health and Environmental Chemicals in Korea; POPs = persistent organic pollutants; FGR = fetal growth retardation; PBDEs = polybrominated diphenyl ethers; RICHS = Rhode Island Child Health Study; As = arsenic; Cd = cadmium; Pb = lead; Mn = manganese; Hg = mercury; Zn = zinc; NHBCS = New Hampshire Birth Cohort Study; Se = selenium; Cu = copper; TSS = transcription start site; ELGAN = Extremely Low Gestational Age Newborns; SES = socioeconomic status; CD = circadian disruption