Bisphenol B and bisphenol AF exposure enhances uterine diseases risks in mouse

Bisphenol A (BPA) analogs, bisphenol B (BPB) and bisphenol AF (BPAF) have been widely detected in the environment and human products with increasing frequency. However, uterine health risks caused by BPB and BPAF exposure need to be further elucidated. The study aimed to explore whether BPB or BPAF exposure will induce adverse outcomes in uterus. Female CD-1 mice were continuously exposed to BPB or BPAF for 14 and 28 days. Morphological examination showed that BPB or BPAF exposure caused endometrial contraction, decreased epithelial height, and increased number of glands. Bioinformatics analysis indicated that both BPB and BPAF disturbed the immune comprehensive landscape of the uterus. In addition, survival and prognosis analysis of hub genes and tumor immune infiltration evaluation were performed. Finally, the expression of hub genes was verified by quantitative real-time PCR (qPCR). Disease prediction found that eight of the BPB and BPAF co-response genes, which participated in the immune invasion of the tumor microenvironment, were associated with uterine corpus endometrial carcinoma (UCEC). Importantly, the gene expression levels of Srd5a1 after 28-day BPB and BPAF exposure were 7.28- and 25.24-fold higher than those of the corresponding control group, respectively, which was consistent with the expression trend of UCEC patients, and its high expression was significantly related to the poor prognosis of patients (p = 0.003). This indicated that Srd5a1 could be a valuable signal of uterus abnormalities caused by BPA analogs exposure. Our study revealed the key molecular targets and mechanisms of BPB or BPAF exposure induced uterine injury at the transcriptional level, providing a perspective for evaluating the safety of BPA substitutes.