Maternal exposure to nanosized titanium dioxide suppresses embryonic development in mice

Figures & data

Table 1 Effects of nano-TiO₂ on element contents in maternal serum, placenta, and fetus

	Index	Nano-TiO2 (mg/kg BW)
		0	25	50	100
Maternal serum	Ti (ng/mL)	0.05±0.00	1.51±0.04***	2.06±0.07***	3.25±0.09***
	Ca (μg/mL)	157.81±7.11	148.73±8.95	136.87±6.21*	129.86±5.59*
	Zn (μg/mL)	1.71±0.06	1.63±0.04	1.51±0.05*	1.46±0.03*
Placenta	Ti (ng/g placenta)	0.08±0.00	15.98±1.06***	22.03±1.73***	35.07±2.31***
	Ca (μg/placenta)	302.27±13.79	250.13±8.22*	176.42±1.29***	163.51±1.71***
	Zn (μg/placenta)	109.35±5.31	98.28±7.05	59.61±2.15**	52.76±1.53**
Fetus	Ti (ng/g fetus)	0.01±0.00	10.25±0.35***	14.59 ±0.89***	21.53±0.72***
	Ca (μg/fetus)	246.13±8.95	232.22±6.66	214.61±8.12*	205.79±7.53*
	Zn (μg/fetus)	85.61±3.35	80.36±2.71	70.66±1.89*	65.17±2.34*

Notes: Results marked with an asterisk, double asterisks, or three asterisks mean they are significantly different from the control (no nano-TiO₂) at the p<0.05, p<0.01, and p<0.001 confidence level, respectively. Values represent mean ± SD (n=5).

Abbreviations: nano-TiO₂, nanoscale titanium dioxide; BW, body weight; SD, standard deviation.

Table 2 Effects of nano-TiO₂ on maternal weight (g) gain during pregnancy

Day of pregnancy	Nano-TiO2 (mg/kg BW)
	0	25	50	100
0	27.62±1.04	27.13±1.15	26.98±1.06	27.46±0.92
3	28.96±1.01	28.65±1.13	28.55±1.12	28.91±0.82
6	31.35±1.15	31.27±1.22	31.08±1.05	31.12±1.06
9	34.51±1.23	34.08±1.19	33.95±1.29	33.32±1.18
12	42.98±1.57	42.08±0.99	41.45±1.55	40.77±13.2
15	53.69±2.06	51.58±1.18	51.09±1.71	48.96±1.28*
18	64.71±2.51	60.11±2.07*	59.32±2.14*	56.79±2.15*

Notes: Results marked with an asterisk mean that they are significantly different from the control (no nano-TiO₂) at the p<0.05 confidence level. Values represent mean ± SD (n=5).

Abbreviations: nano-TiO₂, nanoscale titanium dioxide; BW, body weight; SD, standard deviation.

Table 3 Effects of nano-TiO₂ on fetal growth of mice

Index	Nano-TiO2 (mg/kg BW)
	0	25	50	100
Fetal crown–rump length (cm)	2.42±0.11	2.16±0.13*	1.73±0.08**	1.59±0.09**
Fetal cauda length (cm)	0.77±0.03	0.76±0.02	0.56±0.02*	0.49±0.01**
Fetal body weight (g)	1.35±0.04	1.37±0.03	1.31±0.03	1.24±0.02*
Placental weight (mg)	105.23±4.15	98.08±4.32	81.08±1.17*	80.16±2.53*

Notes: Results marked with an asterisk or double asterisks mean they are significantly different from the control (no nano-TiO₂) at the p<0.05 and p<0.01 confidence level. Values represent mean ± SD (n=5).

Abbreviations: nano-TiO₂, nanoscale titanium dioxide; BW, body weight; SD, standard deviation.

Table 4 Effects of nano-TiO₂ on survival and mortality in mouse fetus

Index	Nano-TiO2 (mg/kg BW)
	0	25	50	100
Number of live fetuses	12.98±0.39	12.73±0.34	11.89±0.31	10.35±0.36*
Number of dead fetuses	0.29±0.01	0.31±0.01	0.51±0.02**	0.55±0.01**
Number of resorption sites	0.41±0.02	0.43±0.01	1.32±0.04**	1.39±0.04**

Notes: Results marked with an asterisk or double asterisks mean they are significantly different from the control (no nano-TiO₂) at the p<0.05 and p<0.01 confidence level. Values represent mean ± SD (n=5).

Abbreviations: nano-TiO₂, nanoscale titanium dioxide; BW, body weight; SD, standard deviation.

Table 5 Effects of nano-TiO₂ on skeletal ossification in mouse fetuses (n=10)

	Index	Nano-TiO2 (mg/kg BW)
		0	25	50	100
Cranial brain	Frontal bone	Obvious ossification	Lamellar ossification	Lamellar ossification	Small and reticulate ossification
	Parietal bone	Most ossification	Incomplete ossification	Small and reticulate ossification	Incomplete ossification; or unossified
	Occipital bone	Ossification of the base, occipital condyle, and squama	Ossification of the base and occipital condyle; incomplete partial squamous ossification	Condylar ossification, incomplete ossification of the base	Condylar ossification
	Nasal bone	Ossification	Ossification	Ossification	Small extent of ossification
Pharyngeal skull	Maxillary bone	Ossification	Small extent of ossification	Punctate ossification	Discontinuous ossification
	Mandible	Ossification	Ossification	Ossification	Partial ossification
Axial bone	Vertebrae	Ossification of the cervical, sacral, and thoracolumbar arches	Ossification of the neck, sacrum, and part of the thoracolumbar arches	Ossification of the cervical, sacral, and lumbar arches	Thoracolumbar ossification
	Rib	Ossification	Ossification	Ossification	Ossification
Limb bone		Ossification from limb to phalanx	Ossification from limb to metatarsal bone	Small extent of ossification from limb to metatarsal bone	Small extent of ossification from limb to metatarsal bone

Abbreviations: nano-TiO₂, nanoscale titanium dioxide; BW, body weight.

Figure 1 Maternal exposure to nano-TiO₂ induced dysplasia of skeleton in mice embryos at gestational day 18.

Notes: Blue indicates cartilage. Purplish red indicates ossification. Red indicates incomplete ossification.

Abbreviations: nano-TiO₂, nanoscale titanium dioxide; BW, body weight.