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At least 19 recordsLinked to original sources
PubMed1997

Disposition and metabolism of finasteride in dogs.

Finasteride (FIN) is a potent 5 alpha-reductase inhibitor that has shown clinical success in treating men with benign prostatic hyperplasia. In the study of biological effects and metabolism of FIN in animals, the dog serves as the primary modality. This study was conducted to determine the pharmacokinetics and fate of FIN after oral administration of single doses of [14C]FIN to dogs at 10 and 80 mg/kg (N = 2 and 3, respectively), and also after intravenous infusion at 5 mg/kg (N = 2). Plasma, urine, and feces were analyzed for total 14C content. Parent drug and metabolites in plasma and excreta were measured by HPLC/UV/radioassay and identified by NMR spectroscopy and MS, FIN was subject to extensive biotransformation before excretion. Structures were determined for the major metabolites in plasma, urine, and feces. The primary metabolic events for FIN were hydroxylation of the t-butyl side chain to give hydroxymethyl-FIN (metabolite I), which is oxidized further to form the carboxylic acid derivative (metabolite IV), and hydroxylation at positions B alpha and 15. Terminal half-life of FIN after the intravenous dose was 3.4 hr. Plasma clearance and volume of distribution at steady-state were 4.8 ml/min/kg and 1.1 liter/kg. Dogs showed rapid absorption after oral administration of the low dose, with Cmax reached in the 1-2 hr, bioavailability was estimated to be > 90%. After either dosing route, 45% of the plasma radioactivity (as represented by AUC) was parent drug, 43% was metabolite I, and 1% was metabolite IV. After oral administration, the 80 mg/kg dose was absorbed slowly, with the highest levels of radioactivity in plasma reached in 4-30 hr. Average Cmax value for FIN and metabolite I increased in a dose-related, but nonproportional, manner. Compared with the 10 mg/kg dose, it seems the higher dose was reasonably well-absorbed, as indicated by the nearly proportional increase of AUC values of total radioactivity and FIN. Composition of plasma metabolites observed at the 80 mg/kg dose level was similar to that observed previously for the low dose, suggesting that an increase in plasma exposure was effected in dogs receiving FIN at 80 mg/kg in toxicity studies. Most of the administered radioactivity was recovered in feces after all doses. Little of the intravenous and low oral doses, but > 50% of the 80 mg/kg oral dose, was excreted as intact FIN, suggesting that metabolism might have been saturated at the high dose.

Animals↗
PubMed2025

Fins as a reliable surrogate tissue for age-related changes of telomeres and DNA methylation in gonads of a short-lived fish.

Senescence is a multifactorial and individualised process of age-related physiological decline. Cellular markers, such as telomere length and DNA methylation, can reveal subtle changes associated with chronological age or expected lifespan. In this study, we evaluated the utility of fin tissue as a surrogate for assessing telomere length and proportion of DNA methylation in the gonads of a small, short-lived laboratory fish, the turquoise killifish (Nothobranchius furzeri). We collected fin and gonadal tissues from both females and males at three different ages. We extracted DNA to measure telomere length via terminal restriction fragment (TRF) analysis and global DNA methylation levels using double-digest restriction-associated DNA sequencing (ddRADseq). Our results show a notable correspondence between telomere length and DNA methylation patterns in fin and gonadal tissues. These findings support the use of fin biopsies as a non-lethal method for assessing ageing biomarkers in the gonads of small freshwater fish.

Animals↗
PubMed2024

Teleost Hox code defines regional identities competent for the formation of dorsal and anal fins.

The dorsal and anal fins can vary widely in position and length along the anterior-posterior axis in teleost fishes. However, the molecular mechanisms underlying the diversification of these fins remain unknown. Here, we used genetic approaches in zebrafish and medaka, in which the relative positions of the dorsal and anal fins are opposite, to demonstrate the crucial role of hox genes in the patterning of the teleost posterior body, including the dorsal and anal fins. By the CRISPR-Cas9-induced frameshift mutations and positional cloning of spontaneous dorsalfinless medaka, we show that various hox mutants exhibit the absence of dorsal or anal fins, or a stepwise posterior extension of these fins, with vertebral abnormalities. Our results indicate that multiple hox genes, primarily from hoxc-related clusters, encompass the regions responsible for the dorsal and anal fin formation along the anterior-posterior axis. These results further suggest that shifts in the anterior boundaries of hox expression which vary among fish species, lead to diversification in the position and size of the dorsal and anal fins, similar to how modulations in Hox expression can alter the number of anatomically distinct vertebrae in tetrapods. Furthermore, we show that hox genes responsible for dorsal fin formation are different between zebrafish and medaka. Our results suggest that a novel mechanism has occurred during teleost evolution, in which the gene network responsible for fin formation might have switched to the regulation downstream of other hox genes, leading to the remarkable diversity in the dorsal fin position.

Animals↗
PubMed2026

Transcriptome analysis of the pectoral fin degeneration in half-smooth tongue sole (Cynoglossus semilaevis).

Appendage degeneration is a notable morphological feature of some teleosts with specialized benthic lifestyles. The half-smooth tongue sole (Cynoglossus semilaevis) undergoes severe pectoral fin regression during metamorphosis. However, the molecular basis underlying rapid pectoral fin degeneration remains unclear. Here, we performed time-series transcriptome sequencing on pectoral fins at pre-metamorphosis, metamorphosis peak and post-metamorphosis to characterize the molecular changes associated with pectoral fin degeneration. Transcriptional dynamics and functional enrichment showed that no significant enrichment of classical apoptosis-related transcriptional pathways was detected during pectoral fin degeneration. Instead, sustained downregulation of twist1b, identified as a transcriptomic candidate, together with significant upregulation of ssh1, coupled with enrichment of lysosome and ubiquitin-proteasome system (UPS) pathways, suggested enhanced tissue remodeling during pectoral fin degeneration. Temporal expression clustering revealed heterochronic misalignment in the developmental gene expression: upstream initiator tbx5 was upregulated at early metamorphosis, while downstream maintenance signal fgf10 decreased synchronously. Distal patterning gene hoxd12a exhibited premature expression and rapid decay, losing sustained late-phase expression. Moreover, transient elevation of gli3 during metamorphosis may contribute to restricted distal fin growth. We conclude that pectoral fin degeneration in C. semilaevis is associated with heterochronic disruption of developmental signaling and extensive tissue remodeling. This study provides transcriptomic insights into pectoral fin degeneration in tongue soles and establishes a basis for future functional studies of appendage reduction in teleosts.

Animals↗
PubMed2026

The convergent evolution of the pelvic suction cup: A unique key innovation in spiny-finned fishes.

Key innovations open ecological opportunities and can redirect evolutionary trajectories. In spiny-finned fishes, the pelvic suction cup-a fused adhesive structure formed from the pelvic fins and supported by a modified girdle-appears to be one such trait. Using a novel 960-species phylogeny spanning 940 exons and 67 newly sequenced snailfish genomes, we show that the suction cup evolved independently three times across lineages separated by over 100 million years. By enabling adhesion in high-energy habitats such as tide pools and waterfalls, the suction cup set the stage for body depression and accompanying shifts in scales, teeth, and clade-specific ecofunctional profiles. Comparative analyses reveal convergence in a distinctive region of morphospace and body-shape evolution accelerated two- to fivefold. Diversification analyses uncover heterogeneous but elevated rates, with a clear burst in rock-climbing gobies associated with suction cup evolution. By opening novel habitats and fostering phenotypic novelty, the suction cup emerges as a key innovation that reshaped spiny-finned fish evolution.

Animals↗
PubMed2026

Genomic Tracking of Market-Derived Bull Shark Fins Back to Source Population of Origin.

International trade of shark fins remains difficult to monitor because products are rarely labelled to species and are often highly processed, resulting in severely degraded DNA. For several shark species listed under Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), this limits external verification of source populations supplying global trade hubs. Here, we assess whether nuclear genomic approaches can be applied to market-derived bull shark (Carcharhinus leucas) fins to determine their population of origin. We analysed dried fin trimmings collected from retail vendors in Hong Kong SAR, one of the world's largest dried shark fin trade hubs, using a targeted DArTcap single nucleotide polymorphism (SNP) panel, originally developed for population genomic studies of this species. Despite substantial DNA degradation, genomic libraries were successfully obtained for most samples, yielding sufficient SNP data to perform robust provenance and sex assignment. Using a Bayesian mixed-stock analysis, most fin samples were assigned to the Indo-West Pacific (71.4%), with smaller contributions from the western Atlantic (22.6%) and eastern Pacific (3.0%). Genetic sex assignment revealed twice as many males as females, although results indicated a conservative bias towards male assignment due to the limited number of X-linked markers available in degraded samples. Our results demonstrate that genome-wide targeted approaches can be effectively applied to highly processed shark fin products to infer population sources and sex composition. This study provides proof-of-concept for integrating genomics into shark trade monitoring, highlighting its potential to improve traceability, support CITES implementation and inform conservation and fisheries management, particularly for species with well-resolved population structure.

Animals↗
PubMed2025

Comparative Genomic Screening Identifies Developmental Constraint Loci Underscoring the Phenotypic Evolution of Syngnathids.

Seahorses and their relatives (syngnathids) exhibit remarkable diversity in morphology and function, characterized by their distinctive body shapes and specialized feeding mechanisms. Despite recent advances in uncovering the genetic basis of some traits, the genotype-phenotype map in syngnathids remains incomplete. In this study, we employed forward-genomic approaches and developed a method to enrich for human disease amino acid loci at a genomic scale. Our aim was to identify genetic loci associated with fin size reduction, tooth loss, and spinal curvature in syngnathids. Intriguingly, we identified a convergent amino acid change in the lat4a gene shared by syngnathids and some flying fishes, with in vitro analysis confirming its role in fin size evolution in both lineages. While genes critical for tooth development are conserved in syngnathids, the absence of key regulatory elements, such as pitx2, likely contributes to tooth loss. Additionally, we implicated col6a3 in spinal curvature development in seadragons. These findings reveal novel genetic signatures and developmental constraints underlying syngnathid diversity, demonstrating the utility of comparative genomics and targeted gene enrichment in exploring vertebrate evolution.

Animals↗
PubMed2026

Integrative analysis of transcriptome and DNA methylome dynamics during caudal fin regeneration in silver pomfret (Pampus argenteus).

Caudal fin regeneration in teleost fish is a complex, multi-stage process involving coordinated molecular and cellular changes. While the role of epigenetic regulation particularly DNA methylation has been studied in model freshwater species such as zebrafish, its contribution to regeneration in marine teleosts remains largely unexplored. In this study, we integrated transcriptomic and DNA methylomic data to characterize the temporal dynamics of gene expression and methylation during caudal fin regeneration in the silver pomfret (Pampus argenteus). Using RNA-sequencing and reduced representation bisulfite sequencing (RRBS) at three biologically critical time points 1, 3, and 7 days post-amputation (dpa), we characterized the spatiotemporal molecular landscape of caudal fin regeneration. These time points capture the key transitional phases of wound healing and inflammation (1 dpa), blastema formation and progenitor proliferation (3 dpa), and regenerative outgrowth with tissue remodeling (7 dpa), enabling robust detection of the major molecular programs underlying epimorphic regeneration. Concurrently, CG-methylome analysis identified thousands of dynamically changing differentially methylated regions (DMRs). A strong global inverse correlation was observed between promoter methylation and gene expression. Integrative analysis pinpointed key regeneration genes (fgf20a, msxb, sox9b) whose expression was associated with dynamic methylation changes in their promoters or gene bodies. We conclude that DNA methylation is a dynamic and key regulatory layer that acts in concert with transcriptional reprogramming to coordinate tissue regeneration, providing new insights into the epigenetic mechanisms underlying complex regenerative processes in teleosts.

Animals↗