Table 3 Basic characteristics of the 50 animal studies investigating maternal-fetal transfer of ambient (ultra)fine particles and engineered NPs

 [44]

CD-1 mice

18

Al₂O₃ NPs

20.9 ± 9.5 or 112.4 ± 24.5^b

nasal drip/ 0 or 50 mg/kg/ 14 days before mating-PND0^g

AAS

/

Higher Al levels in hippocampi of pups from mice exposed to Al₂O₃ NPs before and during pregnancy compared to control pups.

 [45]

CD-1 mice

29

Ag NPs/ citrate

50^b

i.v./ 0, 1.2, or 2.2 mg/kg/ GD7–9^d

ICP-MS

TEM and EDX

Distribution of Ag NPs to most maternal organs and extra-embryonic tissues without significant fetal accumulation.

 [46]

CD-1 mice

40

Ag NPs/ citrate

10^a

i.v./ 0 or 2.2 mg/kg/ GD7–9^d

ICP-MS

Hyperspectral microscopy imaging

No transfer of Ag NPs across the placenta in large amounts but accumulation in the visceral yolk sac and maternal tissue.

 [47]

C57Bl/6 mice

12–15

Ag NPs

19.3 ± 2.3^b

nose-only inhalation/ 0 or 0.64 mg/m³ for 1 or 4 h/day/ GD0.5–14.5^e

spICP-MS and ICP-MS

TEM/EDX

Ag NPs identified and quantified in placenta, yet very low fetal levels.

 [48]

Sprague Dawley rats

40

Ag NPs/ citrate

55^b

oral/ 0, 0.2, 2, or 20 mg/kg/ GD7–20^d

AAS

/

Higher Ag tissue contents in all treated groups compared to control dams and pups, indicating transplacental Ag NP transfer.

 [49]

Wistar rats

12

Ag NPs/ chitosan

19.5 ± 6.72^b

i.p./ 0 or 100 mg/kg/ GD 6, 8, and 10^d

AAS

TEM

Coated and plain Ag NPs detected in significantly higher levels in maternal tissues, placenta, and fetuses compared to control rats. Chitosan coating decreased the silver content significantly.

 [50]

Wistar Rats

60

Ag NPs/ citrate

20 ± 4^a

oral/ 0 or 25 mg/kg/ GD1–19^d

ICP-MS

/

Silver content in the rat offspring’s liver of exposed group differs significantly from control group, suggesting a transplacental transfer of Ag NPs.

 [51]

Sprague Dawley rats

36

Ag NPs/ PVP

20 or 110^a

i.v./ 0 or 1 mg/kg/ GD18^d and oral/ 0 or 10 mg/kg/ GD18^d

ICP-MS

/

Ag NPs measured in the rat placenta and fetuses for both NP sizes. Concentration of Ag NPs in the placenta higher than measured in blood or fetuses for both administration routes.

 [52]

Sprague Dawley rats

8

Ag NPs/ citrate

7.9 ± 0.95^b

oral/ 0 or 250 mg/kg/ 14 days before mating-PND4^d

ICP-MS

TEM

Accumulation of Ag NPs observed in pups of exposed dams with decreasing concentrations from kidney, lung, liver to brain.

 [53]

Wistar rats

7

Ag NPs/ PVP and [^110mAg]

34.9 ± 14.8^b

oral/ 1.69 or 2.21 mg/kg/ GD20^g

Gamma spectroscopy

/

Ag NPs identified in fetuses of pregnant rats in amounts significantly exceeding the detection limit.

 [54]

Wistar rats

30

Ag NPs

4.32 to 16.9^b

i.v./ 0 or 2 mg/kg/ GD19^d

ICP-OES

TEM

Time-dependent increase in fetal Ag NP levels, reaching a peak 6 h after injection and showing a decline afterward.

 [55]

CD-1 mice

16

Au NPs

19.6 or 49.3^a

i.v./ 0 or 100 mg/kg/ GD16–17^g

ICP-MS

AMG

Higher amount of Au NPs in maternal livers and placentae from mice injected with 20 nm compared to 50 nm NPs without detectable levels in fetal organs for both sizes.

 [56]

C57Bl/6 mice

13

Au NPs

2 or 40^a

i.v./ 0, 12.13, or 58.21 mg/mouse/ GD17^g

/

AMG

No accumulation of both Au NP sizes in fetuses nor placentae.

 [57]

Wistar-Kyoto rats

12

Au NPs/S-TPP and [¹⁹⁸Ag]

1.4, 18, or 80^a

i.v./ 0.005 or 0.025 mg/rat/ GD18^g

Gamma spectroscopy

/

All three Au NP sizes found in placenta of pregnant rats. Fractions of 1.4 and 18 nm Au NPs but not 80 nm Au NPs found in the fetuses.

 [58]

C57Bl/6 mice

18

Au NPs/ PEG

3, 13, or 30^a

i.v./ 0.9 mg/kg/ GD17^g

ICP-MS

TEM

All three Au NP sizes reached the placenta of pregnant mice, but fetal Au NP concentrations were negligible.

 [59]

Albino rats

15

Au NPs/ PEG

5.1 ± 0.6 or 32.0 ± 3.6^b

i.v./ 0 or 0.8 mg/kg/ GD10^g

AAS

AMG

Both Au NP sizes penetrate the rat placenta. Higher Au NP levels in maternal tissues (e.g., spleen) compared to fetal tissues.

 [60]

CD-1 mice

25

Au NPs/ PEG

30^b

i.v./ 0 or 5 mg/kg/ GD5.5–7.5 and 11.5–13.5^e

ICP-MS

TEM

Quantitative detection of Au NPs in fetal tissue after exposure during early and late pregnancy. Qualitative visualization of Au NPs in fetal brain and liver.

 [61]

CD-1 mice

156

Au NPs/ PEG, citrate, or ferritin

13^b

i.v./ 0, 0.9, or 7.2 mg/kg/ GD5.5–15.5^e

ICP-MS

TEM, in vivo fluorescence imaging, fluorescence microscopy, and X-ray microscopy

Accumulation of the three Au NP types in extra-embryonic tissue and fetus according to surface composition. Higher Au NP levels during early gestation compared to late gestation.

 [62]

Kunming mice

48

CdTe/CdS core/shell QDs/ MPA, SiO₂, or PEG

1.67 ± 0.29, 2.59 ± 0.43, 3.21 ± 0.32, 4.09 ± 1.02, or 4.20 ± 0.86^b

i.v./ 0, 0.02, 0.05, 0.086, or 0.125 mg/mouse/ GD21^g

ICP-OES

In vivo fluorescence imaging

Quantitative Cd detection in mice pups after maternal injection with QDs. Cd accumulation increased with decreasing size and increasing dosage of injected QDs. Qualitative assessment unable to demonstrate intact QDs in fetuses.

 [63]

Kunming mice

10

CdSe/CdS/ZnS core/shell/shell QDs/ phospho-lipid micelle

n.d.

i.v./ 0 or 0.81 mg/kg/ 14 days before mating^d

/

Bright-field light microscopy and fluorescence microscopy

No QD accumulation in the placenta following prenatal IV injection of QDs in mice.

 [64]

Kunming mice

10

CdSe/ZnS core/shell QDs

13^b

i.v./ 0 or 12.5 nmol/mouse/ GD13-GD18^d

ICP-MS

/

Significant elevations in placental Cd levels for pregnant mice exposed to QDs.

 [65]

Kunming mice

20

CdSe and CdSe/ZnS QDs

n.d.

i.v./ 0 or 0.1 nmol/mouse/ GD16–17^d

ICP-MS

/

Cd detected in the placenta after exposure to different types of QDs. But no significant difference in fetal Cd levels for the exposed group compared to the control group.

 [66]

CD-1 mice

15 to 63

CdO NPs

11.0 ± 0.1 or 15.3 ± 0.1^c

nose-only inhalation/ 0, 0.1 mg/m³ for 1.25 h every other day or 0.23 mg/m³ for 2.5 h/day/ GD4.5–16.5^e

AAS, ICP-MS

/

Cd accumulation in mouse uterus and placenta, as well as other maternal organs, in an associated way with inhaled CdO NPs. CdO NPs were undetectable in fetuses.

 [67]

BALB/c mice

56

CeO₂ NPs

3–5^b

i.v./ 0 or 5 mg/kg/ GD5–7^f

ICP-MS

/

CeO₂ NPs detected in decidual tissue and placentas of IV treated mice during early gestation.

 [68]

C57Bl/6 mice

19

Cu NPs

35.6 ± 1.7^c

whole-body inhalation/ 0 or 3.5 mg/m³ for 4 h/day/ GD3–19^f

ICP-MS

/

No quantitative detection of Cu in the placental nor fetal tissue of exposed mice.

 [69]

CD-1 mice

80

Fe₂O₃ NPs/PEI or PAA

n.d.

i.p./0 or 10 mg/kg/ GD9 or 9–16^d

UV-vis spectrophoto-meter

Bright-field light microscopy

Both Fe₂O₃ NP types crossed the placenta. Only mice treated with PEI-NPs for eight consecutive doses showed a significant increase in Fe levels in fetal livers and placentae.

 [70]

Wistar rats

8

MMSNPs/ [^99mTc]

58.9 ± 8.1^b

i.v./ 0 or 18.5 MBq/mL/ GD11 or 20^g

Gamma spectroscopy

/

SiO₂ NPs crossed the placenta of pregnant rats, both during early and late stages of gestation. SiO₂ NPs reach the fetal bloodstream and bioaccumulate in both embryos and fetuses.

 [71]

C57Bl/6 mice

11

MMSNPs/ gadolinium oxide-core and TFP

100–200^b

i.v./ 0 or 1 mg/mouse/ GD7–9 or 14–15^d

MRI and ultrasound imaging

/

SiO₂ NPs observed in embryos of mice following early gestation injections while being excluded from the embryo by the placenta following late gestation injection.

 [72]

CD-1 mice

44

Pt NPs

20.9 ± 11.4^a

oral/ 0, 0.25, 0.5, or 1 mg/kg/ 14 days before mating-PND4^g

ICP-MS

/

No detection of Pt NPs in pups of mice orally exposed before, during, and after gestation.

 [73]

BALB/c mice

n.d.

SiO₂ and TiO₂ NPs/ fluorophore

35, 70, 300, or 1000^a

i.v./ 0 or 0.8 mg/mouse/ GD16 or 16–17^g

/

In vivo fluorescence imaging, fluorescence microscopy, and TEM

Only smaller SiO₂ and TiO₂ NPs found in the placenta, fetal liver, and fetal brain.

 [74]

CD-1 mice

70

SiO₂ NPs/ amine or carboxyl

25, 60, or 115^a

i.v./ 0 or 0.2 mg/mouse/ GD5.5, 12,5, or 16.5^e

ICP-OES

/

SiO₂ NPs administered at different gestational stages reached placenta and fetus. Biodistribution influenced by NP size, surface charge, and gestational stage.

 [75]

Wistar rats

30

TiO₂ NPs

21^b

oral/ 0 or 200 mg/kg/ GD6–12^d

/

TEM and SEM/EDX

TiO₂ NPs bypass the placenta and reached late-term neonatal rat lung tissue.

 [76]

CD-1 mice

20

TiO₂ NPs

6.5^a

oral/ 0, 25, 50, or 100 mg/kg/ GD0–17^d

ICP-MS

/

Significantly increased Ti content in placenta and fetus with received TiO₂ NP dose compared to controls.

 [77]

C57Bl/6 mice

45

TiO₂ NPs

97^c

Whole-body inhalation/ 0 or 42 mg/m³ for 1 h/day/ GD8–18^g

ICP-MS

/

No quantitative detection of Ti in mice pups following maternal inhalation of nanosized TiO₂.

 [78]

Wistar rats

12

TiO₂ NPs

10^a

oral/ 0 or 100 mg/kg/ GD2–21^g

ICP-MS

/

Ti accumulated in hippocampus of rat offspring after gestational TiO₂ NP exposure.

 [79]

C57Bl/6 mice

15

TiO₂ NPs

5–6^b

i.v./ 0, 0.1, or 1 mg/mouse/ GD9^d

SF-ICP-MS

/

No significant accumulation of Ti in maternal plasma, placenta, fetal liver, and fetal brain for the 3 groups exposed to different concentrations of TiO₂ NPs.

 [80]

CD-1 mice

12

TiO₂ NPs

25–70^a

s.c./ 0 or 0.1 mg/mouse/ GD3, 7, 10, and 14^g

/

FE-SEM/EDX

TiO₂ NP transfer from pregnant mice into the brain and testis of their offspring.

 [81]

SPF mice

20

TiO₂ NPs

5.5^a

oral/ 0, 1.25, 2.5, or 5 mg/kg/ prenatal day 7-PND21^g

ICP-MS

/

Maternal gestational exposure to TiO₂ NPs enhanced Ti content in offspring’s’ hippocampi.

 [82]

Sprague Dawley rats

4

ZnO NPs/ citrate

20^a

oral/ 0 or 400 mg/kg/ GD5–19^d

ICP-OES

/

No significant difference in fetal Zn content between control and ZnO NP exposed group.

 [83]

Sprague Dawley rats

10

ZnO NPs/ APTES

> 35^a

i.v./ 0 or 20 mg/kg/ GD6–20^d

ICP-MS

/

Significantly elevated Zn levels in fetal liver after IV injection of pregnant rats with ZnO NPs.

 [84]

Sprague Dawley rats

24

ZnO NPs

< 100^a

oral/ 0 or 500 mg/kg/ 14 days before mating-day 4 of lactation^g

ICP-MS

/

Significantly higher levels of Zn in liver and kidneys, but not in blood and brain of rat offspring exposed to ZnO NPs before, during, and after gestation.

 [85]

CD-1 mice

40

ZnO NPs

13.2 ± 3.7, 57.1 ± 4.1, or 1900 ± 504^b

oral/ 0 or 7.2 mg/mouse/ GD1–10 or 7–16^f

ICP-MS

/

Zn detected in the placentae of mothers exposed to ZnO NPs during early gestation in contrast to mothers exposed to bulk ZnO. Only the smallest ZnO NPs crossed the placenta to reach the fetus.

 [86]

CD-1 mice

60

ZrO₂ NPs

16 ± 4^b

oral/0, 2.5, 25, or 50 mg/kg/ GD9–11, GD13–15, or GD16–18^f

ICP-MS

TEM/EDX

Fetal accumulation of ZrO₂ NPs following oral exposure of pregnant mice during different stages of pregnancy.

 [87]

Sprague Dawley rats

30

Fullerene/ [¹⁴C(U)]

26 ± 7^b

i.v./ 0 or 0.2 mg/kg/ GD11, 15, or 18^g

Gamma spectroscopy

/

Radioactive signals from C60 NPs detected in placenta and fetuses of exposed pregnant dams. Stronger signal 24 h compared to 8 days post-injection.

 [88]

Sprague Dawley rats

8

Fullerene/ [¹⁴C(U)]

< 10^a

i.v./ 0 or 0.3 mg/kg/ GD 15^g

Gamma spectroscopy

/

Radioactive signals detected in the placenta and fetuses of pregnant dams, indicative of transplacental C60 NP transfer.

 [89]

Wistar rats

24

PGMA NPs/PEI, fluorophore, and magnetite core

n.d.

i.v./ 0 or 0.5 mg/rat/ GD10 or 20^f

MRI and fluorescence microscopy

Ex vivo fluorescence imaging and confocal microscopy

Both PGMA NP types detected in the rat conceptus during early gestation. Greater accumulation of cationic NPs within the chorionic plate than anionic NPs.

 [27]

FVB/N mice

40

PS NPs/ carboxyl and fluorophore

20, 40, 100, 200, and 500^a

i.v./ 0.3 mg/mouse/ GD17^g

HPLC and fluorescence microscopy

/

Placental uptake and transfer of fluorescent PS NPs with diameters up to 500 nm. NPs observed in various organs of fetuses after 4 h of administration to pregnant mice.

 [90]

Mice

15

PS NPs/ fluorophore and PEG or carboxyl

50–70^a

i.v./ 0 or 0.00231 mg/kg/ GD10–15^g

/

Confocal microscopy

Both PS NP types found in placenta but not in embryonic tissues.

 [91]

New-Zealand white rabbits

8

DEP

69^c

nose-only inhalation/ 0 or 1 mg/m³ for 2 h/day, 5 days/week/ GD3–27^g

/

TEM

NP-like structures observed in olfactory tissues of fetuses from DEP exposed mothers.

 [92]

New-Zealand white rabbits

n.d.

DEP

69^c

nose-only inhalation/ 0 or 1 mg/m³ for 2 h/day, 5 days/week / GD3–27^g

/

TEM

NP-like structures observed in placenta, maternal blood space, trophoblasts and fetal blood of exposed rabbits.