Fluoride-Induced Autophagy and Apoptosis in the Mouse Ovary: Genomic Insights into IL-17 Signaling and Gut Microbiota Dysbiosis

Ommati M. M., Zuo Q., Sabouri S., Retana-Marquez S., Nategh Ahmadi H., Gholami A., ...daha çox

Journal of Agricultural and Food Chemistry, vol.73, no.3, pp.2138-2155, 2025 (SCI-Expanded, Scopus) identifier identifier

  • Nəşrin Növü: Article / Article
  • Cild: 73 Say: 3
  • Nəşr tarixi: 2025
  • Doi nömrəsi: 10.1021/acs.jafc.4c10165
  • jurnalın adı: Journal of Agricultural and Food Chemistry
  • Jurnalın baxıldığı indekslər: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Analytical Abstracts, Applied Science & Technology Source, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, Compendex, Environment Index, Food Science & Technology Abstracts, Pollution Abstracts, Veterinary Science Database, DIALNET
  • Səhifə sayı: pp.2138-2155
  • Açar sözlər: colon microbiota, developmental toxicity, dysbiosis, female reprotoxicity, fluorosis
  • Açıq Arxiv Kolleksiyası: Məqalə
  • Adres: Bəli

Qısa məlumat

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.