Effects of maternal exposure to arsenic on social behavior and related gene expression in F2 male mice

Abstract

Background Arsenic is a developmental neurotoxicant. It means that its neurotoxic effect could occur in offspring by maternal arsenic exposure. Our previous study showed that developmental arsenic exposure impaired social behavior and serotonergic system in C3H adult male mice. These effects might affect the next generation with no direct exposure to arsenic. This study aimed to detect the social behavior and related gene expression changes in F2 male mice born to gestationally arsenite-exposed F1 mice. Methods Pregnant C3H/HeN mice (F0) were given free access to tap water (control mice) or tap water containing 85 ppm sodium arsenite from days 8 to 18 of gestation. Arsenite was not given to F1 or F2 mice. The F2 mice were generated by mating among control F1 males and females, and arsenite-F1 males and females at the age of 10 weeks. At 41 weeks and 74 weeks of age respectively, F2 males were used for the assessment of social behavior by a three-chamber social behavior apparatus. Histological features of the prefrontal cortex were studied by ordinary light microscope. Social behavior-related gene expressions were determined in the prefrontal cortex by real time RT-PCR method. Results The arsenite-F2 male mice showed significantly poor sociability and social novelty preference in both 41-week-old group and 74-week-old group. There was no significant histological difference between the control mice and the arsenite-F2 mice. Regarding gene expression, serotonin receptor 5B (5-HT 5B) mRNA expression was significantly decreased (p < 0.05) in the arsenite-F2 male mice compared to the control F2 male mice in both groups. Brain-derived neurotrophic factor (BDNF) and dopamine receptor D1a (Drd1a) gene expressions were significantly decreased (p < 0.05) only in the arsenite-F2 male mice of the 74-week-old group. Heme oxygenase-1 (HO-1) gene expression was significantly increased (p < 0.001) in the arsenite-F2 male mice of both groups, but plasma 8-hydroxy-2′-deoxyguanosine (8-OHdG) and cyclooxygenase-2 (COX-2) gene expression were not significantly different. Interleukin-1β (IL-1β) mRNA expression was significantly increased only in 41-week-old arsenite-F2 mice. Conclusions These findings suggest that maternal arsenic exposure affects social behavior in F2 male mice via serotonergic system in the prefrontal cortex. In this study, COX-2 were not increased although oxidative stress marker (HO-1) was increased significantly in arsnite-F2 male mice.

Gestational arsenic exposure induces anxiety-like behaviors in F1 female mice by dysregulation of neurological and immunological markers

“…The reason for high doses setting is lower susceptibility of mice to arsenic [ 42 ]. As mentioned above, in our previous and present studies, NaAsO 2 , 85 ppm was given to F0 pregnant mice from gestational days 8–18 to detect carcinogenicity, reproductive and neurotoxicity in F1 and F2 offspring [ 33 , 34 , 43 – 45 ]. This is a standard dose to detect the effects of gestational exposure to arsenic without maternal toxicity and teratogenicity.…”

“…Control mice (n = 7) were given tap water only. The experimental dose for gestational arsenic exposure was explained in our previous studies [ 33 , 34 , 38 ]. The experimental design of this study was illustrated in the Fig.…”

“…Moreover, gestational arsenic exposure showed sex-dependent neurotoxicity due to the resistance of epigenetic reprogramming of the glucocorticoid signaling system [ 31 , 32 ]. In our previous report, we showed that gestational arsenic exposure causes the neurotoxicity and social behavior impairment in the F1 and F2 male mice [ 33 , 34 ].…”

Bioinformatic analyses of hydroxylated polybrominated diphenyl ethers toxicities on impairment of adrenocortical secretory function

“…In recent years, with the development of various high throughput technologies, high throughput screening for toxicological relationships has been possible through genome analysis of the bioinformatics, rapid mapping of biological pathways and genes involved in toxicological interference, and effective analysis of mechanisms and pathways [27][28][29][30][31]. Global transcriptome sequencing analysis (RNA-seq) can effectively discern potential biomarkers, filter related biopathways, and help us probe the potential toxic mechanism [32].…”

Early Low-Level Arsenic Exposure Impacts Post-Synaptic Hippocampal Function in Juvenile Mice

“…Even mild increases in arsenic exposure are of concern, as exposure is associated with numerous adverse health outcomes and increased mortality from a variety of conditions, including cardiovascular disease and cancer, as well as increased infant mortality [ 4 ]. Further, recent studies suggest the consequences of arsenic exposure can span across generations [ 6 , 7 , 8 ].…”