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

Journal of Agricultural and Food Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

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 fluoride-exposed female mice. To explore these mechanisms, F0 pregnant mice were exposed deionized water (control) or 100 mg/L sodium (NaF) during gestation throughout F1 generation (n = 16 females/group), covering puberty weaning maturity. NaF caused reductions body weight, organ coefficients, pathological indices, with increased ovarian autophagic vacuoles, mitochondrial injuries, elevated serum/ovary LPS levels females. qRT-PCR, fluorescent staining, biochemical assays, Western blotting confirmed signaling, autophagy. Moreover, 16S rRNA sequencing revealed gut microbiota dysbiosis NaF-exposed potentially exacerbating ovary injury via serum elevation. The could justify deteriorated its connection F-induced injury. These findings provide mechanistic insights into reprotoxicity, emphasizing interplay apoptosis disrupting cellular homeostasis suggesting potential therapeutic targets.

Язык: Английский

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Fluoride induces spermatocyte apoptosis by IP3R1/MCU-mediated mitochondrial calcium overload through MAMs

Journal of Hazardous Materials, Год журнала: 2025, Номер 489, С. 137514 - 137514

Опубликована: Фев. 5, 2025

Язык: Английский

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Combined exposure of PS-MPs with NaF induces Sertoli cell death and dysfunction via ferroptosis and apoptosis

Toxicology, Год журнала: 2024, Номер 506, С. 153849 - 153849

Опубликована: Май 29, 2024

Язык: Английский

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Effects of fluoride toxicity on the male reproductive system: A review

Journal of Trace Elements in Medicine and Biology, Год журнала: 2024, Номер 86, С. 127522 - 127522

Опубликована: Сен. 7, 2024

Язык: Английский

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Fluoride-induced testicular and ovarian toxicity: evidence from animal studies

Biological Research, Год журнала: 2025, Номер 58(1)

Опубликована: Янв. 25, 2025

Abstract Fluoride (F), as a natural element found in wide range of sources such water and certain foods, has been proven to be beneficial preventing dental caries, but concerns have raised regarding its potential deleterious effects on overall health. Sodium fluoride (NaF), another form F, the ability accumulate reproductive organs interfere with hormonal regulation oxidative stress pathways, contributing toxicity. While exact mechanisms F-induced toxicity are not fully understood, this review aims elucidate involved testicular ovarian injury. In males, F exposure at different doses associated reduced testis weight, sperm quality terms count, motility, viability, well abnormal morphology disruption seminiferous tubules by altering hormone levels (especially testosterone), impairing spermatogenesis, inducing zinc deficiency. Similarly, administration can impact female health affecting function, levels, oocyte quality, regularity estrous cycle. However, LH, FSH, GnRH is controversial between males females. both females, exerts adverse triggering apoptosis, autophagy, inflammation, mitochondrial dysfunction, reduction ATP synthesis, modulation important genes steroidogenesis. Furthermore, genetic susceptibility individual variations metabolism may contribute responses exposure.

Язык: Английский

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Interplay of Ferroptosis, Cuproptosis, Autophagy and Pyroptosis in Male Infertility: Molecular Crossroads and Therapeutic Opportunities

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3496 - 3496

Опубликована: Апрель 8, 2025

Male infertility is intricately linked to dysregulated cell death pathways, including ferroptosis, cuproptosis, pyroptosis, and autophagy. Ferroptosis, driven by iron-dependent lipid peroxidation through the Fenton reaction inactivation of GPX4/Nrf2/SLC7A11 axis, disrupts spermatogenesis under conditions oxidative stress, environmental toxin exposure, or metabolic disorders. Similarly, cuproptosis—characterized mitochondrial dysfunction disulfide stress due copper overload—exacerbates germ apoptosis via FDX1 activation NADPH depletion. Pyroptosis, mediated NLRP3 inflammasome gasdermin D, amplifies testicular inflammation loss IL-1β/IL-18 release, particularly in response insults. Autophagy maintains homeostasis clearing damaged organelles proteins; however, its dysregulation impairs sperm maturation compromises blood–testis barrier integrity. These pathways intersect shared regulators; reactive oxygen species mTOR modulate autophagy–pyroptosis balance, while Nrf2 bridge ferroptosis–cuproptosis crosstalk. Therapeutic interventions targeting these mechanisms have shown promise preclinical models. However, challenges persist, tissue-specific roles isoforms, off-target effects pharmacological inhibitors, transgenerational epigenetic impacts toxins. This review synthesizes current molecular insights into implicated male infertility, emphasizing their interplay translational potential for restoring spermatogenic function.

Язык: Английский

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Fluoride induces immunotoxicity by regulating riboflavin transport and metabolism partly through IL-17A in the spleen

Journal of Hazardous Materials, Год журнала: 2024, Номер 476, С. 135085 - 135085

Опубликована: Июль 3, 2024

Язык: Английский

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