Light pollution impairs ovarian function via m6A-dependent miR-421-5p processing-mediated clock disruption

Apr 15, 2026Chronobiology international

Light pollution may harm ovary function by disrupting the body’s clock through a specific RNA process involving miR-421-5p

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Abstract

Light-exposed female rats showed a 40% decrease in estradiol and a 1.5-fold increase in testosterone levels.

Disrupted estrous cycles and irregular follicular development were observed in light-exposed rats.
Increased ovarian m6A levels were identified alongside upregulated METTL14 and a 50% reduction in CLOCK expression.
Altered processing of miRNA led to elevated levels of mature miR-421-5p in both light-exposed rats and rat ovarian granulosa cells.
In human KGN cells, knockdown of METTL14 suppressed m6A methylation and enhanced CLOCK expression, restoring granulosa cell function.
Overexpression of METTL14 exacerbated CLOCK suppression and cellular dysfunction via increased miR-421-5p levels.

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Light pollution disrupts circadian rhythms and impairs ovarian function, but the underlying molecular mechanisms remain unclear. This study investigates whether the METTL14-miR-421-5p-CLOCK axis mediates these effects. Female rats were exposed to normal or continuous light. Estrous cycles, ovarian morphology, and hormone levels were assessed, alongside analysis of METTL14, miR-421-5p, and CLOCK expression. In human KGN granulosa cells,was knocked down or overexpressed to examine its role in miR-421-5p maturation, and CLOCK regulation. Cell viability, migration, and apoptosis were measured. Light-exposed rats exhibited disrupted estrous cycles, irregular follicular development, and hormonal imbalance, with a 40% decrease in Eand a 1.5-fold increase in testosterone. Ovarian m6A levels increased, with upregulatedand a 50% reduction inexpression. Altered miRNA processing was observed, leading to elevated mature miR-421-5p. Similar phenomena were also observed in rat ovarian granulosa cells. In KGN cells,knockdown suppressed m6A methylation and miR-421-5p maturation, thereby increasing CLOCK expression and restoring granulosa cell function. Conversely,overexpression exacerbated miR-421-5p-mediated CLOCK suppression and cellular dysfunction. Light pollution upregulates METTL14, enhancing m6A-dependent maturation of miR-421-5p, which post-transcriptionally represses CLOCK. This novel epi-transcriptomic mechanism disrupts steroidogenesis and ovulation, offering new insights for preventing pollution-related reproductive diseases. METTL14Mettl14Clock METTL14METTL14 2