Table 9:
Multi- and transgenerational effects of Pb, PFAS, and phthalates
| Factor | Window of exposure | Model | Epigenetic/molecular effect | Phenotype | Sex specificity | Reference |
|---|---|---|---|---|---|---|
| Pb, measured in maternal (reflecting grandmother’s exposure) and child (reflecting mother’s exposure) neonatal dried blood spots, as well as child blood | Gestation | Human | Altered DNA methylation in the blood of grandchildren at genes associated with cardiovascular development and disease (NDRG4, APOA5, NINJ2, and TRPV2) | Not investigated | Not reported | [128] |
| F0 generation exposed as embryos to Pb(NO3)2) in water at 10 μM | <2 h post-fertilization until 24 h | Zebrafish | In embryos, differential expression of genes involved in epigenetic modifications in F2 generation; genes associated with CVD significantly differentially expressed in F2 females | Not investigated | Yes | [240] |
| 100 ppm Pb acetate dissolved in distilled deionized drinking water | 2 months prior to mating | Mouse | Altered DNA methylation of Th in the cortex in F3 females; altered DNA methylation of Bdnf in the hippocampus of F3 males | Reduced body weight; decreased corticosterone in F3 females | Yes | [241] |
| PFBS (0, 1.0, 2.9, and 9.5 μg/l) exposure in F0 generation | Embryo stage until reaching sexual maturity (6 months of age) | Zebrafish | Reduced global DNA methylation levels in F1 embryos | Decreased weight in F1 generation eggs; increased weight of F2 eggs | Yes—effects on F0 female reproduction | [243] |
| PFBS (0.0005, 0.01, 0.1, 0.5, 1, and 2 mM—equivalent to 0.15, 3.0, 30.0, 150, 300, and 600 mg/l) in growth medium | L4 stage larvae were exposed for 48 h | C. elegans | Not investigated | Movement defects in F1 generation; reduced lifespan in F4 and F5 generations continuously exposed to low-dose PFBS | Not reported | [244] |
| PFBS and PFHxS in growth medium (1 ng/l) | Egg stage, for 72 h | C. elegans | In larvae, altered expression of enzymes and genes important for lipid metabolism | Not investigated | Not reported | [70] |
| 6:2 chlorinated polyfluorinated ether sulfonate (F-53B, 0, 5, 50, or 500 μg/l) | 180 days | Zebrafish | Altered expression of thyroid axis genes in F1 and F2 embryos/larvae | Increased T4 levels in F1 embryos; increased mortality, impaired swim bladder formation, increased T3 and T4 levels in F1 larvae; impaired swim bladder formation in F2 larvae | Not reported | [245] |
| Levels of PFAS in serum from partners of pregnant women | Paternal exposure | Human | Negative association between PFNA and global sperm DNA methylation in all populations combined; positive association between PFOA and LINE-1 methylation in Kharkiv; negative association between PFHxS and sperm global DNA methylation in Greenland; negative association between PFOS and sperm global DNA methylation in Warsaw; positive association between PFOS and satellite alpha repeat methylation in Kharkiv | Not investigated | Only males were evaluated | [247] |
| Di-n-butyl phthalate (0 and 500 mg/kg) or corn oil vehicle via oral gavage | Gestational days 8–14 | Rat | Increased levels of betaine and betaine homocysteine S-methyltransferase, global DNA hypomethylation in F1 and F3 testis at 60 days of age | Decreased sperm counts in F1–F3 generation at 60 days of age | Only males were evaluated | [248] |
| DEHP (500 mg/kg) or corn oil vehicle by oral gavage | Gestational days 7–14 | Mouse | Not investigated | Decreased sperm count and mobility in F1–F4 generations; impaired spermatogonial stem cell function in F3 | Only males were evaluated | [249] |
| DEHP (20 and 200 µg/kg/day and 500 and 750 mg/kg/day) or corn oil control by oral gavage | Gestational day 10.5 until birth | Mouse | Not investigated | Accelerated puberty, disruptions in estrous cycle, and decreased markers of fertility in F1 and F2; increased litter size in F2; accelerated puberty, disruptions in estrous cycle and decreased anogenital distance in female offspring | Only females were evaluated | [250] |
| DEHP (1, 20, 50, or 300 mg of DEHP/kg/day) or oil control by oral gavage | Gestational day 14 until birth | Rat | Not investigated | Decreased rate of pregnancy, lower body weight, increased litter size, and decreased pup weight in F3 | Only females were evaluated | [251] |
| Phthalate mixture: 35% DEP, 21% DEHP, 15% DBP, 8% DiBP, 15%DiNP, and 5% BzBP (20 μg/kg–500 mg/kg) or corn oil vehicle via oral gavage | Gestational day 10 until birth | Mouse | Not investigated | Decreased testosterone and inhibin B, increased follicle stimulating hormone and luteinizing hormone in F1; lower testosterone and reduced percentage of antral follicles in F2; altered estrous cycle, increased ovarian weight, decreased luteinizing hormone, altered numbers of follicles in F3 | Only females were evaluated | [252] |
| DEHP (150 and 200 mg/kg) or corn oil control daily via oral gavage | Gestational days 7–14 | Mouse | Higher pituitary Gnas expression with stress and ancestral DEHP exposure in both F3 sexes | Lower corticosterone concentrations after stress in F3 females; dose-dependent behavioral changes and reduced seminal vesicle weights in F3 males | Yes | [254] |
| DEHP (0 and 40 μg DEHP/kg) or 0.1% DMSO vehicle daily via oral gavage | From 0.5 to 18.5 days after mating | Mouse | Reduced DNA methylation in Igf2r and Peg3 regulatory regions in F1 male and female primordial germ cells and in F2 oocytes | Not investigated | Yes | [256] |