Aflatoxin B1 disrupts testicular development via the cell cycle-related Ras/PI3K/Akt signaling in mice and pig

Aflatoxins B1 (AFB1), a type I carcinogen widely present in the environment, not only poses a danger to animal husbandry, but also poses a potential threat to human reproductive health, but its mechanism is still unclear. To address this question, multi-omics were performed on porcine Sertoli cells and mice testis. The data suggest that AFB1 induced testicular damage manifested as decreased expression of GJA1, ZO1 and OCCLUDIN in mice (p < 0.01) and inhibition of porcine Sertoli cell proliferation. Transcriptomic analysis suggested changes in noncoding RNA expression profiles that affect the cell cycle-related Ras/PI3K/Akt signaling pathway after AFB1 exposure both in mice and pigs. Specifically, AFB1 caused abnormal cell cycle of testis with the characterization of decreased expressions of CCNA1, CCNB1 and CDK1 (p < 0.01). Flow cytometry revealed that the G2/M phase was significantly increased after AFB1 exposure. Meanwhile, AFB1 downregulated the expressions of Ras, PI3K and AKT both in porcine Sertoli cell (p < 0.01) and mice testis (p < 0.01). Metabolome analysis verified the alterations in the PI3K/Akt signaling pathway (p < 0.05). Moreover, the joint analysis of metabolome and microbiome found that the changes of metabolites were correlated with the expression of flora. In conclusion, we have demonstrated that AFB1 impairs testicular development via the cell cycle-related Ras/PI3K/Akt signaling.

Automated summary

The study found that Aflatoxins B1 (AFB1) leads to damage in porcine Sertoli cells and mice testis, resulting in decreased expression of GJA1, ZO1, and OCCLUDIN, and inhibition of porcine Sertoli cell proliferation. Transcriptomic analysis revealed changes in noncoding RNA expression profiles that affect the cell cycle-related Ras/PI3K/Akt signaling pathway in response to AFB1 exposure in both mice and pigs. AFB1 also caused abnormal cell cycle in the testis, with decreased expressions of CCNA1, CCNB1, and CDK1, and an increased G2/M phase. Furthermore, metabolome analysis confirmed alterations in the PI3K/Akt signaling pathway.