Transplacental and genotoxicity effects of thallium(I) during organogenesis in mice

Abstract

The increased concentration of thallium (Tl) in the environment is a cause for concern because the entire population, including pregnant women, is exposed, and this metal crosses the placenta and reaches the conceptus during development. In biological models such as mice, some abnormalities and delays in ossification occur in the fetuses of mice administered Tl on day 7 of gestation, but exposure to environmental Tl is constant during fetal development; therefore, in this study, the effects of several administrations of TI during organogenesis on the external morphology, skeletal development and genotoxicity of fetuses were evaluated. Four groups of 10 pregnant mice were administered 5.28, 6.16, 7.4 or 9.25 mg/kg body weight Tl(I) acetate intraperitoneally during fetal organogenesis. Additionally, samples were taken from fetuses from pregnant mice treated with 5.28 and 6.16 mg/kg body weight to evaluate the transplacental genotoxicity. The results revealed that the 9.25 mg/kg body weight dose produced maternal and fetal toxicity, and all of the treatment groups presented relatively high percentages of fetuses with external abnormalities, reduced bone ossification, and an increased percentage of liver cells with structural chromosomal aberrations (SCAs) and micronuclei (MNs) in blood cells. These results show that Tl(I) acetate administered during organogenesis produces abnormalities, including a delay in ossification and transplacental genotoxicity, in mouse fetuses. These findings are important because Tl has negative effects on development and may affect the health of offspring in the future because it can damage genetic material.

Keywords: Abnormalities in offspring; Chromosomal aberrations; Delayed ossification; Maternal toxicity; Micronucleus; Thallium(I) acetate.

Graphical abstract

Fig. 1

Experimental design.

Fig. 2

Fetuses with bone and cartilage variations from dams treated with Tl(I) acetate during fetal organogenesis. SS, single-staining; DS, double-staining. The treated groups were different from the control, with * p < 0.05 for the control vs. the treated groups according to the chi-square test.

Fig. 3

Cytogenetic analysis of A: Number of polychromatic erythrocytes (PCEs). B: Micronuclei (MN-PCEs) counted in a total of 2000 PCEs in blood samples from fetuses obtained from pregnant mice treated with doses of 5.28 and 6.16 mg/kg bw Tl(I) acetate during fetal organogenesis. * p < 0.05 control vs. treated group according to the ANOVA-Dunnett test.

Fig. 4

Micrographs of blood erythrocytes stained with acridine orange: a) MNs in the polychromatic erythrocytes MN-PCE, b) PCEs, c) MNs in the normochromatic erythrocytes MN-NCE, and d) NCE. Fluorescence microscope, magnification 100x.

Fig. 5

Cytogenetic analysis of the mitotic index (MI) and structural chromosomal aberrations (SCAs) in liver samples from fetuses obtained from pregnant mice treated with 5.28 and 6.16 mg/kg bw Tl(I) acetate during fetal organogenesis. A: MI and MI inhibition (MII). B: SCAs with gaps and without gaps. * p < 0.05 control vs. treated group according to ANOVA-Tukey test for the SCAs. The Z test was used to compare the MI.

Fig. 6

Structural chromosomal aberrations (SCAs) in the liver cells of fetal mice treated with Tl. A) metaphase of the control group without SCA, B) chromatid breakage, C) fragmentation, and D) deletion. The microscope magnification was 100x.