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. 2021 Jan 3;42(3):295–353. doi: 10.1210/endrev/bnaa035

Table 4.

Early and late gestational presence of endocrine-disrupting chemicals and their associations with placental changes

EDC Classes Inflammatory and oxidative state Hormonal and metabolomic changes Epigenetic changes
Early Mid to late /term Early Mid to late /term Early Mid to late /term
Metals Maternal TM1 As: ↑8-oxoguanine, IL1B, TNF, IFNG (355)
Maternal TM1 Tl: ↑ CD68; ↓ IL4 AND CD206 (496)
Maternal TM2 Co: ↓CCL2, IL6 and TNF (497)
Placental Mn: CD68 colocalication with Mn (499)
Placental Cd: ↑ Di- and nitrotyrosine; ↓antioxidants (34)
Maternal TM3 As: ↑8-oxoguanine and IL1B (355)
Maternal TM3 Tl: ↑ TNF, IL6 and CD68 (496)
Placental Cd: ↓ placental progesterone production (500); ↓ leptin (502)
Maternal TM3 As:↑leptin (355)
Maternal urine Pb: ↓ methylation at 9 CpGs (513) Placental Cd: 17 differentially methylated CpG sites with ↑ TNFAIP2, EXOC3L4, GAS7, SREBF1, ACOT7, and RORA (506) ↑ miR-1537 and ↓ let-7 family members (514)
Placental Hg: ↓ let-7 family members (514)
Parabens ∑parabens ↑miR-128 (512)
PAHs Placental benzopyrene: ↑ oxidant malondialdehyde and ↓ antioxidant glutathione (216) Cord-blood PAHs: ↑IGF1 and IGFBP3 (501)
Phytoestrogens
Bisphenols TM2 aborted fetus BPA: ↑ miR-146a and 33 other miRNAs (511)
Placenta BPA ↑ LINE1 methylation (515)
Maternal ∑phenols: ↑miR-128; ↓miR-142, miR-15a-5p (512)
Phthalates Maternal MBP: ↑mRNA expression of IL1B, IL6, and CRP (♂); ↑IL6, CRP, CCL2, IL8, IL10, and CD68 (♀) (495)
Maternal MEOHP: ↓ CRP, CCL2, CD68 mRNA (♀) (495)
Maternal MBzP: ↑TNF, CCL2 and CD68 mRNA (♂) (495)
Maternal MEHHP, MEOHP, MECPP, ΣDEHP: ↓PlGF (379) Maternal MnBP: U-shaped dose–response with steroidogenic genes (322)
Maternal MEHHP, MEOHP, MECPP, ΣDEHP: ↓PlGF (379)
Terminated pregnancy ∑phthalates: 2214 differentially methylated single CpG sites; 282 differentially methylated regions (518) MEOHP or MEP: ↓ IGF2DMR0 methylation (♂ and ♀) (509)
Maternal ∑LMP (MiBP, MnBP, MEP): ↑miR-185 (512)
Maternal MECPP, MEHHP, MEHP: ↓IGF2DMR0 methylation (♀)
(509)
Maternal MCNP and MHiBP: ↑ placental lncRNAs (510)
Maternal DEHP: ↓ LINE1 methylation (516)
Organohalogens Placental PBDE: ↓ T4 (examined in males only) (163)
Cord PBDE: ↑IGF1 and IGFBP3 (501)
Placental PBDE: ↑ global DNA methylation (507)
Placental PCB: ↑ H19 methylation (507)
Maternal BDE ↑ DIO3 methylation (♀) (507)
Maternal POP: 214 differentially methylated CpG sites (517)
Maternal PBDE ↑ miR-188-5p ↓ let-7c; PCB ↑ miR-1537 (514)
Agro- chemicals Placental methoxychlor: ↓ free T3 (♂ examined) (163) Maternal DDE: ↑ DIO3 methylation (♀) (508)
Maternal DDT: ↑ MCT8 methylation (♂) (508)
Antifouling agents Placental tributyltin and ∑organotin: ↓ free T3 (♂ examined) (163)
Personal care products see above sections for effects of parabens, bisphenols and phthalates
Pharmaceuticals see above sections for effects of bisphenols and phthalates

Abbreviations: ↑, increase; ↓, decrease; ≠, no association; ∑, sum; ♂, male; ♀, female; CRP, C-reactive protein; DDE, diphenyl dichloro ethylene; DEHP, phthalate di(2-ethylhexyl)-phthalate; Early, first trimester; EDC, endocrine-disrupting chemical; IFNG, interferon γ; IGF1, insulin-like growth factor; IL, interleukin; mid to late, second and third trimester; mRNA, messenger RNA; miRNA, microRNA; PAHs, polyaromatic hydrocarbons; PBDE, polybrominated diphenyl ether; PCB, polychlorinated biphenyl; T3, 3,5,3′-triiodothyronine; T4, thyroxine; TM, trimester; TNF, tumor necrosis factor.