Fluoride-Induced Autophagy and Apoptosis in the Mouse Ovary: Genomic Insights into IL-17 Signaling and Gut Microbiota Dysbiosis
Makaleler > Tam Makale · 2025
Yazarlar: Mohammad Mehdi Ommati, Qiyong Zuo, Samira Sabouri, Socorro Retana-Marquez, Socorro Retana-Marquez, Hassan Nategh Ahmadi, Ahmad Gholami, Azız EFTEKHARIMEHRABAD, Sina Shojaei, Liu Lijuan, Reza Heidari, Hong Wei Wang
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Scopus, 2025, cilt 73, ss 2138-2155
Özet
Chronic fluoride (F) exposure is linked to gonadotoxicity in females, yet the underlying molecular mechanisms remain unclear. This study investigated fluoride-induced reprotoxicity using advanced genomic profiling. RNA-seq analysis identified significant activation of autophagy, apoptosis, and IL-17 signaling pathways in fluoride-exposed female mice. To explore these mechanisms, F0 pregnant mice were exposed to deionized water (control) or 100 mg/L sodium fluoride (NaF) during gestation and throughout the F1 generation (n = 16 females/group), covering puberty to weaning and maturity. NaF exposure caused significant reductions in body weight, organ coefficients, and pathological indices, with increased ovarian autophagic vacuoles, mitochondrial injuries, and elevated serum/ovary LPS levels in F1 females. qRT-PCR, fluorescent staining, biochemical assays, and Western blotting confirmed the activation of IL-17 signaling, apoptosis, and autophagy. Moreover, 16S rRNA sequencing revealed gut microbiota dysbiosis in NaF-exposed F1 females, potentially exacerbating ovary injury via serum LPS elevation. The gut dysbiosis could justify deteriorated serum LPS levels and its connection to F-induced ovary injury. These findings provide mechanistic insights into fluoride-induced reprotoxicity, emphasizing the interplay of IL-17 signaling, autophagy, and apoptosis in disrupting cellular homeostasis and suggesting potential therapeutic targets.