https://doi.org/10.1007/s12011-026-05070-0
SEE:Abstract
Chronic fluorosis can cause ovarian damage, leading to incorrect hormone levels, follicle dysplasia, reduced fertility, and other diseases. This study analyzed the molecular mechanism of LKB1-AMPK in regulating mitochondrial damage in fluoride-treated SVOG and KGN ovarian cells and Sprague-Dawley rats. The cytotoxic effect of sodium fluoride (NaF) on SVOG and KGN cells was assessed using Cell Counting Kit-8 (CCK-8), crystal violet, and 5-ethynyl-2’-deoxyuridine (EdU) staining. Cell cycle progression and apoptosis were evaluated through flow cytometry and western blotting. Mitochondria levels were assessed by mitochondrial staining. Reactive oxygen species (ROS) levels, oxidative stress, and inflammatory markers were measured by ROS staining, microplate reader assays, and western blotting. The rat body weight, ovarian size and wet weight, and fluorosis were recorded, the oxidative stress index was detected, ovarian damage was examined using hematoxylin and eosin staining and electron microscopy, and protein expression was investigated through western blotting. The NaF was toxic to the SVOG and KGN cells, inhibiting their proliferation ability, halting cell cycle progression, triggering apoptosis, and promoting cell oxidative stress (detected through ROS, superoxide dismutase, malondialdehyde, glutathione peroxidase, and total antioxidant capacity assays) to inhibit the antioxidant-related proteins NQO-1 and HO-1 and promote the expression of the inflammation-related proteins IL-1 and IL-6. Compared to the control group, the fluoride-exposed group had lower mitochondrial fluorescence intensity, decreased LKB1, AMPK, and SIRT1 protein expression, and increased FOXO1A protein expression. Furthermore, the fluoride-exposed group had lower LKB1 and AMPK immunofluorescence intensity than the control group. The high fluoride concentration caused dental fluorosis, induced oxidative stress, and damaged the ovary and mitochondria in the rats. The western blotting demonstrated that the fluoride exposure decreased LKB1, AMPK, and SIRT1 protein expression levels and increased FOXO1A protein expression levels in the rat ovarian tissue. The mechanism of ovarian fluorine damage may be the inhibition of LKB1-AMPK pathway activity, regulation of the downstream SIRT1 and FOXO1A protein expression, mitochondrial dysfunction, oxidative stress and inflammation, and induction of apoptosis in ovarian cells.
SIRT
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