Mechanismof reproductive toxicity of sub-chronic exposure to nickel oxide nanoparticles in male SD rats
10. 20001/j. issn. 2095⁃2619. 20224004
- Author:
fan xingjun
;
gu hongmei
;
yang yong
- Publication Type:Journal Article
- Keywords:
Nickel oxide nanoparticles;Testicular;Sex hormones;B-cell lymphoma-2;BCL-2 associated X protein;Cell cycle;Apoptosis;Rat
- From:
China Occupational Medicine
2022;49(2):140-147
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of sub-chronic exposure of nickel oxide nanoparticles (Nano NiO) on
endocrine function of male SD rats,and to analyze the toxicity and mechanism of Nano NiO on testicular cells. Methods The
specific pathogens free male SD rats were randomly divided into five groups with ten rats in each group. Rats in low-,medium
and
high-dose groups were given Nano NiO suspension with the mass concentration of 0.16,0.80 and 4.00 g/L,respectively;
rats in blank control group were given equal volume of 0.9% sodium chloride solution;rats in positive control group were given
micron nickel oxide suspension with the mass concentration of 4.00 g/L. Drip every three days for nine weeks. After the Nano
NiO exposure,atomic fluorescence spectrometry was used to determine the levels of nickel in the blood and testicular tissue. The
enzyme-linked immunosorbent assay was used to detect serum level of sex hormone. The ploidy ratio,cell cycle and apoptosis
rate of testicular cells were analyzed by flow cytometry. Western blotting was used to detect the relative expression of apoptosis
related
proteins in the testis. Results The level of nickel in blood and testicular tissue of rats in positive control group and the
three doses groups were higher than that of blank control group(all P<0.05). The level of nickel in blood and testicular tissue of
rats in the medium-dose and high-dose groups were higher than that in the positive control group(all P<0.05). There was a
positive correlation between the level of nickel in blood and testicular tissue(P<0.01). The serum levels of testosterone,follicle
stimulating
hormone(FSH)and luteinizing hormone(LH)in the medium- and high- dose groups were lower than that in blank
control group(all P<0.05). However,there was no significant difference in serum gonadotropin-releasing hormone among all
groups(P>0.05). Compared with the blank control group,the proportion of haploid and diploid cells and the ratio of cells in G0/
G1 and S phase decreased in the medium- and high-dose groups(all P<0.05),the tetraploid cell ratio,G2/M cell ratio and
early apoptotic rate of testicular cells increased(all P<0.05). Compared with the blank control group,the relative expression of
B-cell lymphoma-2(BCL-2)protein and the ratio of BCL-2/BCL-2-related X protein(BAX)in testicular cells of rats decreased
in the medium- and high-dose groups(all P<0.05),the relative expression of BAX and caspase-3 protein were increased(all P<
0.05). Compared with the positive control group,the level of nickel in blood and testicular tissue of rats was increased in the
high-dose group(all P<0.05),the ratio of haploid cells and the ratio of testicular cells at G0/G1,S phase and BCL-2 /BAX ratio
in testicular tissue decreased(all P<0.05),the tetraploid ratio,G2/M phase ratio,early apoptotic rate and total apoptotic rate
of testicular cells increased(all P<0.05). Conclusion Exposure to Nano NiO could inhibit the secretion of FSH,LH and
testosterone in male rats. Nano NiO can cross the blood-testosterone barrier,interfere with the proliferation of testicular cells,
induce apoptosis of testicular cells through the mitochondrial apoptosis pathway,inhibit the formation of haploid sperm cells,
resulting in disorders of spermatogenesis.