Background Arsenic (As) acts as an environmental endocrine disruptor to exert estrogen-like effects, and its toxic mechanism on target genes of estrogen effect in skin has not been fully elucidated.
Objective This experiment is designed to observe the effects of arsenic exposure and the intervention of 5-Aza-2'-deoxycytidine (5-Aza-dc, an DNA methylation inhibitor) on the expressions of estrogen receptor α (ERα), estrogen receptor β (ERβ) and phosphoinositide 3-kinase (PI3K) mRNA in the skin tissues of rabbits of different sexes, and to explore the roles of estrogen effect target gene mRNA expressions in the sex difference of arsenic skin toxicity.
Methods Rabbits were randomly divided into seven groups:blank control group, low-dose arsenic group (0.075 mg·kg-1·week-1), medium-dose arsenic group (0.15 mg·kg-1·week-1), high-dose arsenic group (0.75 mg·kg-1·week-1), 5-Aza-dc intervention against low-dose arsenic group, 5-Aza-dc intervention against medium-dose arsenic group, and 5-Aza-dc intervention against high-dose arsenic group, with eight animals in each group, half male and half female. The rabbits were given free drinking water and continuously administered the corresponding arsenic dosages for 14 weeks. From the 9th week, the 5-Aza-dc intervention groups received intravenous injection of 0.125 mg·kg-1 5-Aza-dc through ear vein twice a week for six weeks. At the end of the 14th week, biopsy of full-thickness skin was performed on the same region on the back of each rabbit. The expression levels of ERα, ERβ and PI3K mRNA in skin tissues of rabbits of different sexes were detected by real-time fluorescence quantitative PCR (RT-PCR).
Results In the rabbit skin tissues, the expression levels of ERα mRNA in the female low-and high-dose arsenic groups (1.67±0.10 and 2.95±0.38, respectively) and in the male high-dose arsenic group (2.88±0.43) were higher than that in the control group (P < 0.05). The expression levels of ERβ mRNA in the male low-and high-dose arsenic groups (0.75±0.02 and 0.59±0.29, respectively) were lower than those in the control group and in the females with corresponding treatments (0.90±0.08 and 1.48±0.58, respectively) (P < 0.05). The expression level of PI3K mRNA in the male low-dose arsenic group (0.70±0.22) was lower than that in the corresponding female group (1.40±0.10) (P < 0.05). The expression levels of ERβ and PI3K mRNA in the male 5-Aza-dc intervention groups were lower than that in the control group (P < 0.05).
Conclusion Arsenic exposure can induce increased expression of ERα mRNA in the skin tissues of male and female rabbits, and decreased expressions of ERβ and PI3K mRNA in the skin tissues of male rabbits, and both were higher in females than in males. The sex difference of arsenic-induced ERα, ERβ, and PI3K mRNA expressions may play a role in the sex difference of arsenism. Moreover, 5-Aza-dc can further increase the differences between males and females.
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