Chlormequat Chloride Disrupts Testicular Cholesterol Homeostasis and Testosterone Synthesis in Peripubertal Rats: Involvement of the miR-212–5p/STARD7 Axis

Abstract Chlormequat chloride (CCC), a widely used plant growth regulator and suspected endocrine disruptor, has been reported to reduce testosterone in peripubertal rats, yet the underlying mechanisms remain unclear. Here, CCC accumulated dose-dependently in the testes of peripubertal rats, accompanied by reductions in testicular cholesterol and testosterone. In H295R cells, CCC impaired cholesterol uptake and testosterone secretion while downregulating LDLR, StAR, VDAC1, STARD7, and CYP11A1. CCC also upregulated miR-212–5p, which directly targeted the STARD7 3′-UTR at a conserved binding site, as shown by dual-luciferase reporter assays. Inhibition of miR-212–5p partially restored testosterone secretion, whereas STARD7 knockdown further reduced testosterone production under CCC exposure. These findings nominate the miR-212–5p/STARD7 axis as a plausible post-transcriptional node contributing to CCC-induced disruption of cholesterol homeostasis and testosterone synthesis, while the causal relevance of this axis in vivo and direct evidence for impaired mitochondrial cholesterol trafficking remain to be established.