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Finasteride, a steroid 5-alpha reductase inhibitor, is commonly used for the treatment of benign prostatic hyperplasia and hair loss. However, despite continued use, its environmental implications have not been thoroughly investigated. Thus, we investigated the acute and chronic adverse impacts of finasteride on Daphnia magna, a crucial planktonic crustacean in freshwater ecosystems selected as bioindicator organism for understanding the ecotoxicological effects. Chronic exposure (for 23 days) to finasteride negatively affected development and reproduction, leading to reduced fecundity, delayed first brood, reduced growth, and reduced neonate size. Additionally, acute exposure (< 24 h) caused decreased expression levels of genes crucial for reproduction and development, especially EcR-A/B (ecdysone receptors), Jhe (juvenile hormone esterase), and Vtg2 (vitellogenin), with oxidative stress-related genes. Untargeted lipidomics/metabolomic analyses revealed lipidomic alteration, including 19 upregulated and 4 downregulated enriched lipid ontology categories, and confirmed downregulation of metabolites. Pathway analysis implicated significant effects on metabolic pathways, including the pentose phosphate pathway, histidine metabolism, beta-alanine metabolism, as well as alanine, aspartate, and glutamate metabolism. This comprehensive study unravels the intricate molecular and metabolic responses of D. magna to finasteride exposure, underscoring the multifaceted impacts of this anti-androgenic compound on a keystone species of freshwater ecosystems. The findings emphasize the importance of understanding the environmental repercussions of widely used pharmaceuticals to protect biodiversity in aquatic ecosystems.

Riboswitches are segments of noncoding RNA that bind with metabolites, resulting in a change in gene expression. To understand the molecular mechanism of gene regulation in a fluoride riboswitch, a base-pair opening dynamics study was performed with and without ligands using the Bacillus cereus fluoride riboswitch. We demonstrate that the structural stability of the fluoride riboswitch is caused by two steps depending on ligands. Upon binding of a magnesium ion, significant changes in a conformation of the riboswitch occur, resulting in the greatest increase in their stability and changes in dynamics by a fluoride ion. Examining hydrogen exchange dynamics through NMR spectroscopy, we reveal that the stabilization of the U45·A37 base-pair due to the binding of the fluoride ion, by changing the dynamics while maintaining the structure, results in transcription regulation. Our results demonstrate that the opening dynamics and stabilities of a fluoride riboswitch in different ion states are essential for the genetic switching mechanism.