Fluoride exposure during puberty induces testicular impairment via ER stress-triggered apoptosis in mice.

Fluoride, a ubiquitous environmental compound, carries significant health risks at excessive levels. This study investigated the reproductive toxicity of fluoride exposure during puberty in mice, focusing on its impact on testicular development, spermatogenesis, and underlying mechanisms. The results showed that fluoride exposure during puberty impaired testicular structure, induced germ cell apoptosis, and reduced sperm counts in mice. Additionally, the SOD activity and GSH content were significantly decreased, while MDA content was significantly elevated in the NaF group. Immunohistochemistry showed an increase in the number of cells positive for GRP78, a key ER stress marker. Moreover, qRT-PCR and Western blot analyses confirmed the upregulation of both Grp7 8 mRNA and protein expression, as well as increased mRNA expression of other ER stress-associated genes (Grp94 , chop , Atf6 , Atf4, and Xbp1) and enhanced protein expression of phosphorylated PERK, IRE1α, eIF2α, JNK, XBP-1, ATF-6α, ATF-4, and CHOP. In conclusion, our findings demonstrate that fluoride exposure during puberty impairs testicular structure, induces germ cell apoptosis, and reduces sperm counts in mice. ER stress may participate in testicular cell apoptosis, and contribute to the testicular damage and decreased sperm counts induced by fluoride. Fluoride exposure during puberty induces testicular germ cell apoptosis, impairs testicular structure, and reduces sperm count in mice. ER stress may participate in testicular cell apoptosis via activating JNK and CHOP, ultimately contributing to testicular damage and decreased sperm counts in mice caused by fluoride exposure during puberty. [Display omitted] • Fluoride exposure during puberty impairs testis development in mice. • Fluoride exposure during puberty decreases sperm counts in mice. • Fluoride triggers testicular germ cells apoptosis in mice. • ER stress involves in fluoride-induced testicular germ cells apoptosis. [ABSTRACT FROM AUTHOR]