Fluorene-9-bisphenol exposure damages the testis in mice through a novel mechanism of ferroptosis

• Published in: Food and chemical toxicology Vol. 184; p. 114385
• Main Authors: Feng, Qiwen, Liu, Yumeng, Zou, Liping, Lei, Mengying, Zhu, Changhong, Xia, Wei
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2024
• Subjects: Animals; Benzhydryl Compounds; BHPF; Blood-testis barrier; Ferroptosis; Fluorenes - chemistry; Fluorenes - pharmacology; Male; Mice; Phenols; Semen; Sertoli cell; Testis; Testis; Sertoli cell; Ferroptosis; BHPF; Blood-testis barrier
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2023.114385

Fluorene-9-bisphenol (BHPF) is an emerging global endocrine-disrupting chemical found in numerous household products as a substitute of bisphenol A. Many studies have reported various toxicities associated with BHPF. However, the effect of BHPF on male reproduction, particularly on the structural integrity of the blood testis barrier (BTB) in mice, has not yet been extensively studied. Ferroptosis, a newly identified form of cell death, occurs in the testicular tissue following exposure to BPA, affecting male fertility. We investigated whether ferroptosis plays a role in BHPF-induced testicular damage. The findings indicated that BHPF exposure led decreases in serum testosterone (T) concentration and sperm concentration and motility in mice. Furthermore, BHPF disrupted the BTB by interfering with key BTB-related proteins, including Cx43, β-catenin, and ZO-1. Moreover, BHPF induced ferroptosis through the induction of lipid peroxidation, iron overload, oxidative stress, and mitochondrial dysfunction in the testicular tissue. Inhibition of ferroptosis using Fer-1 mitigated the BHPF-induced damage to the BTB and ferroptosis in TM4 cells. Overall, our findings indicated the detrimental effects of BHPF on male reproductive function in mice, suggesting ferroptosis as a mechanism underlying testicular damage. [Display omitted] •BHPF exposure in mice led to decreased sperm concentration and motility.•Ferroptosis played a crucial role in BHPF-induced testicular damage.•BHPF resulted in the dysfunction of the blood-testis barrier through ferroptosis.