Environmental Fluoride Compromises Male Fertility: Differentially Modulated miR-34a-5p Targets REST to Regulate Autophagy in Testicular Somatic Cells.

ABSTRACT: The worldwide decline in male fertility represents a growing public health challenge, with fluoride exposure recognized as a key environmental factor exacerbating this decline. Fluoride hurts male reproduction, yet the specific mechanism remains unclear. Here, we demonstrate that fluoride reduced mouse sperm quality, destroyed the structure of testicular tissue, and caused severe damage to testicular somatic cells (Leydig and Sertoli cells). Meanwhile, the number of autophagosomes increased in Leydig cells and decreased in Sertoli cells. Network toxicology and functional analysis identified miR-34a-5p as the pivotal miRNA orchestrating fluoride-induced autophagic imbalance in testicular somatic cells. REST was identified as a novel miR-34a-5p target gene exhibiting pro-autophagic activity.

SUBMITTER: Cheng A 

PROVIDER: S-EPMC12877340 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature