Table 3.
Early and late gestational presence of endocrine-disrupting chemicals and their associations with maternal and fetal mediators
| EDC classes | Inflammation | Oxidative stress | Hormonal changes | Metabolomic changes | Microbiomic changes | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Early | Mid to late term | Early | Mid to late term | Early | Mid to late term | Early | Mid to late term | Early | Mid to late term | |
| Metals | Maternal: Se, Mo, Cd, Ni, Cu, Zn, Pb ↑ MCP3 and IL8 (334) | Maternal: Se, Mo, Ni ↑ maternal MCP3 (334) Maternal W and U ↓ cord MCP1 (334) Maternal Mo, Ni, Cd, Zn ↑ cord MCP1a and MCP3 (334) Maternal As ↑ IL1B, IL8, IFNG, TNF (355) |
Maternal Pb and Cu ↓ cord nitrotyrosine and chlor- tyrosine (333) | Maternal V, As, Pb ↓ free T3 (36) Maternal As, Se, Mn, Ni, Sb ↓ free and total T3 or T4 (381) Maternal Ce and Yb ↓ cord TSH (382) |
Maternal Cd ↑ urine L-cystine, L-tyrosine, and dityrosine; ↓histamine, and uric acid (256) ↑ uric acid (399) | Maternal toenail As level ↑ butyry- lqlycine and tartrate (400) Maternal TM2: higher Cu and lower Mo: ↑ glucose level (394) Maternal Ar ↑ TM2 cord 17- methylstearate, laurate (12:0) and 4- vinylphenol sulfate (400) |
Maternal Methyl Hg Gut microbiome composition changed (416) | Maternal Methyl Hg No effect on gut microbiome composition (416) | ||
| Parabens | Maternal urine: butyl paraben ↓ CRP (351) Ethyl paraben ↓ IL1B (356) |
Maternal urine: butyl, ethyl, methyl, propyl paraben ↑ 8-hydroxy- deoxyguanosine and 8- isoprostane (362) Maternal term urine: Methyl and ethyl paraben ↑ malondealdehyde (MDA) and 8- hydroxydeoxy- guanosine (63) |
Maternal butyl paraben ↓ E2 and free T4 (375); ↑ total T4 (376) Maternal methyl and propyl paraben ↓ mid-pregnancy E2 and ↑ late-pregnancy E2 (375) Maternal propyl paraben Maternal: ↓ free T4 (376) Maternal term urine: EtPB ↑ cord blood triiodothy- ronine levels (278) |
Maternal urine: Parabens affect purine metabolism, fatty acid β-oxidation, and other pathways: methyl paraben ↑ hypoxanthine and 7- methylxanthine; ethyl paraben ↑ benzoic acid; propyl paraben ↑ trimethylamine N-oxide, dihydrobiopterin, and 2,6-dimethy- lheptanoyl carnitine (401) | Maternal butyl paraben ↑ TM2 glucose Propyl paraben ↓ glucose (353) |
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| PAHs | Placental PAH DNA adducts: ↑ TBARS and 7-ethoxy- coumarin O-deethylase, ↓ glutathione S-transferase activity (367) | Maternal urine: 1- hydroxypyrene ↑ MDA (366, 367); placental 1- hydroxypyrene: ↑8-OHdG (75) | Maternal Hydroxylated PAH ↓ E2 and T (280) | |||||||
| Phytoestrogens | Maternal equal ↑ E3 (84) Maternal matairesinol, enterodiol and entero- lactone ↑ urine hydroxylation products of estrogens (219) |
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| Bisphenols | Maternal BPA ↑ IL6 (350) Maternal BP3 ↓ CRP (351) |
Maternal BPA ↑ 3-nitrotyrosine (364) | Maternal BPA ↑ cord 3-nitrotyrosine (364) Maternal BP3 ↑ 8-hydroxy- deoxyguanosine (8-OHdG) and 8-isoprostane (363) Maternal BPS ↑ 8-isoprostane (363) |
BPA: baseline cortisol↑ in female, baseline cortisol↓ in male (383) Maternal BPF: ↑ free T3 (384) |
Maternal BPA ↓ maternal TSH (369, 370); ↑ maternal free T4 (370) ↓ maternal T (374) ↑ cord E2 (294) Maternal BPA ↓ CRH (364) Maternal BPF ↑ free T4 (364) |
BPA ↑ maternal palmitic acid; oleic acid and total free fatty acids (364) | Maternal BPA ≠ glucose levels (249) ↑ urine - endocanna binoid, palmitoleamide and lysophosphatidy- lethanolamine 18:0 (402) Cord ↓leptin and ↑high-molecular-weight adiponectin (445) |
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| Phthalates | Maternal MnBP, MBzP, MCOMHP, meCPP, MEHP ↑ MCP3 and IL8 (353) | Maternal MnBP, mCINP, meCPP, MEHP, MEHHP, MEOHP ↑ MCP3 (353) Maternal MnBP/ MEHP ↑ cord MCP1a /MCP3 (353) Maternal MnBP, MIP, MNP ↑ 8-iso-prostaglandin F2α (351) |
Maternal MCPP and MCINP ↓ chlor-tyrosine (333) | Maternal MBzP and MCOMHP ↓ cord nitro-tyrosine (333) | Maternal DEHP slower rise in hCG (305) Maternal MiBP, MEHP, MEOHP ↑ E1 and E2 (378) Maternal MBzP ↑ E2 (378) Maternal MCNP and DEHP ↓ free T (378) Maternal urine: MnBP, MBzP, MCIP ↑ hCG (386) |
Maternal MEHP and DEHP ≠ cord E2, T, FSH, LH, T3, T4, and TSH (282) Maternal MEP: ↓ maternal total T4 (372); ↑ total and free T (377) Maternal DEHP: ↓ maternal total and free T (377) |
Maternal MEP ↑ blood glucose (396) Maternal DEHP ↓ triglycerides, palmitic, oleic, linoleic, and α-linolenic acids (397) Maternal MEP, MnBP, MiBP, DEHP ↑ nicotinamide mononucleotide, cysteine T2, cystine, and L-aspartic acid (398) MiBP, MnBP, and DEHP ↓ Cord leptin (445) |
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↓ cord cortisol, cortisone and glucocorticoid/adrenal androgen ratio, and ↑ cord DHEA and DHEA/androstenedione ratio (439) Maternal MBszP ↓ TSH (372) Maternal MEP, MnBP, MiBP, DEHP ↓ total T4 Cord: ↓ TSH and total T4 (372) ↓ androstenedione, T and DHEAS and ↑E2 and E3 (114) |
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| Organohalogens | Maternal PBDE and PFAS ↑ IL6 and TNF (352) | Maternal serum HCB and PCB congeners ↓ total T3 and ↑ free T4 (387) PFOS: ↓ maternal TM3 cortisone (388) |
PFOS and PFNA ↓ newborn TSH (430) PFOA and PFOS Maternal hypothyroid (389) Cord: PFOS ↑ DHEA and cortisol; PFOA ↓ DHEA (441) PCB ↓ newborn T3 and T4 (436,437) ↓ T and ↑ E2 (443) PCDF ↑ maternal 4-hydroxyl E2; PCDD ↓4-hydroxyl E2/ 2-hydroxyl E2 ratio (390) PBDE ↑ cord TSH (436) ≠ maternal and cord E2 (444) |
PBDE ↑ maternal fasting glucose (395) PFAS ↓ maternal glucose (403) PFOS ↑ maternal glucose; PFOS metabolite inverse-U shaped association (404) |
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| Agrochemicals | Maternal HCH, DDD, DDE ↑ IL6 and IL4 (357) Maternal plasma PBDEs ↑ IL6 and TNF; PFAS ↑ IL6; hydroxylated PBDE metabolites ↓ IL10 (352); ≠ CRP (354) |
DDE and HCB maternal (366) and cord (429) ↓ total T3 and T4; ↓ TSH (389) DAP ≠ maternal and cord TSH, T3 and T4 (374) Maternal pyrethroids ↑ TSH (373) Chlordanes, cis-HCB, heptachlor epoxide, Mirex, and toxaphenes Cord: ↓ T, cortisol, cortisone, prolactin, ↑ DHEA, FSH (♂) (442) DDT Cord: ↓ DHEA and ↑ cortisol (♀) (442) |
Maternal urine pesticides: ↑ glycine, threonine, lactate and glycerop- hosphoc- holine and ↓ citrate (405) | |||||||
| Antifouling agents | ||||||||||
| Personal care products | Maternal urine: Triclosan ↑ CRP, IL10, TNF; 2,5- dichlorophenol ↑ CRP (356) | Maternal triclosan ↑ 8-hydroxy- deoxyguanosine (363) | Maternal triclosan ≠ TSH, T3 or T4 (385) | Maternal triclosan ↑ E3 (376) Maternal triclocarban ↑ T3 and T3/T4 (375) |
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| Pharmaceuticals | see sections above 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; E2, estradiol; E3, estriol; Early, first trimester; EDC, endocrine-disrupting chemical; FSH, follicle-stimulating hormone; IFNG, interferon γ; IGF1, insulin-like growth factor; IL, interleukin; MDA, malondialdehyde; mid to late, second and third trimester; mRNA, messenger RNA; miRNA, microRNA; PAHs, polyaromatic hydrocarbons; PBDE, polybrominated diphenyl ether; PCB, polychlorinated biphenyl; PFAS, perfluorinated alkylated substance; PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonic acid; T3, 3,5,3′-triiodothyronine; T4, thyroxine; TM, trimester; TNF, tumor necrosis factor; TSH, thyrotropin.