Microplastics (MPs) have emerged as widespread environmental pollutants, causing significant threats to aquatic ecosystems and organisms. This review examines the toxic effects of MPs on fishes, with a focus on neurobehavioural, physiological, and reproductive impacts, as well as the underlying mechanisms of toxicity. Evidence indicates that MPs induce a range of neurobehavioural abnormalities in fishes, affecting social interactions and cognitive functions. Altered neurotransmitter levels are identified as a key mechanism driving behavioural alterations following MP exposure. Physiological abnormalities in fishes exposed to MPs are also reported, including neurotoxicity, immunotoxicity, and oxidative stress. These physiological disruptions can compromise the individual health of aquatic organisms. Furthermore, reproductive abnormalities linked to MP exposure are discussed, with a particular emphasis on disruptions in endocrine signaling pathways. These disruptions can impair reproductive success in fish species, impacting population numbers. Here we explore the critical role of endocrine disruptions in mediating reproductive effects after exposure to MPs, focusing primarily on the hypothalamic-pituitary-gonadal axis. Our review highlights the urgent need for interdisciplinary research efforts aimed at elucidating the full extent of MP toxicity and its implications for aquatic ecosystems. Lastly, we identify knowledge gaps for future research, including investigations into the transgenerational impacts, if any, of MP exposure and quantifying synergetic/antagonistic effects of MPs with other environmental pollutants. This expanded knowledge regarding the potential risks of MPs to aquatic wildlife is expected to aid policymakers in developing mitigation strategies to protect aquatic species.

Microplastics (MPs) are widespread contaminants in aquatic ecosystems and pose significant threats to both organisms and the environment. Their small size, high surface area, and capacity to adsorb toxic chemicals allow MPs to infiltrate food webs, affecting organisms across trophic levels. This review explores the intricate mechanisms by which MPs induce reproductive and endocrine toxicity, focusing on their physical and chemical properties, bioaccumulation dynamics, and associated molecular pathways. MPs interfere with hormonal homeostasis, oxidative stress responses, and apoptotic pathways, leading to disruptions in the hypothalamic-pituitary-gonadal axis, impaired steroidogenesis, and gonadal dysfunction. These effects manifest as reduced fertility, altered gametogenesis, and multigenerational reproductive impairments across diverse aquatic taxa. Furthermore, MPs serve as carriers for endocrine-disrupting chemicals, compounding their adverse effects on organisms and aquatic biodiversity. Through a synthesis of recent research, this review identifies key signaling pathways, including MAPK, PI3K-AKT, mTOR, NF-κB, PPAR and NLRP3 inflammasome, that may play a role in MP-induced reproductive toxicity. The findings underscore the urgent need for advanced mitigation strategies, regulatory frameworks, and further research to combat the ecological consequences of MP pollution. Prioritizing targeted interventions is essential to safeguard aquatic biodiversity and ensure ecosystem resilience against the pervasive threat of MPs.

Bisphenol S (BPS) is a widely used synthetic compound and is known as an endocrine-disrupting chemical (EDC). The ability of BPS to bind predominantly to estrogen receptors raises significant concern, as it can interfere with different neurological functions, leading to neurobehavioural deficits. Despite extensive research documenting various adverse effects of BPS in adult fish, its neurobehavioural effects, especially in early life stages of fish, remain poorly understood. In the present study, zebrafish embryos (4-hours post fertilization, hpf) were exposed to an environmentally relevant concentration of BPS (30 μg/L), in addition to control and DMSO (0.01%; vehicle control), until 120 hpf, followed by behavioural, biochemical, and molecular assessments. BPS exposure impaired tail coiling frequency in embryos (20 hpf), and thigmotaxis and reflexive movement behaviour (120 hpf) in zebrafish larvae. At 120 hpf, larvae showed elevated reactive oxygen species (ROS), increased apoptosis, and higher malondialdehyde (MDA) levels, indicating lipid peroxidation and oxidative damage. Biochemical analysis further demonstrated that BPS significantly increased whole body serotonin (5-HT) and acetylcholine levels at 120 hpf. Moreover, gene expression analysis at 120 hpf indicated that BPS exposure resulted in the dysregulation of genes involved in dopaminergic, serotonergic and cholinergic neurotransmitter pathways, apoptosis pathway, oxidative stress response, and neuroinflammation. These findings suggest that BPS induces oxidative stress, neuroinflammation and apoptosis, leading to the disruption of neural development and signaling pathways involved in regulating behavioural responses. Overall, our study provides new insights into the behavioural effects and underlying neurotoxic mechanisms of developmental BPS exposure in larval zebrafish.

The cytotoxic T-lymphocyte antigen-4 (CTLA4) is essential in controlling T cell activity within the immune system. Thus, uncovering the molecular dynamics of single nucleotide polymorphisms (SNPs) within the CTLA4 gene is critical. We identified the non-synonymous SNPs (nsSNPs), examined their impact on protein stability, and identified the protein sequences associated with them in the human CTLA4 gene. There were 3134 SNPs (rsIDs) in our study. Out of these, 186 missense variants (5.93%), 1491 intron variants (47.57%), and 91 synonymous variants (2.90%), while the remaining SNPs were unspecified. We utilized SIFT, PolyPhen-2, PROVEAN, and SNAP for identifying deleterious nsSNPs, and SNPs&GO, PhD SNP, and PANTHER for verifying risk nsSNPs in the CTLA4 gene. Following SIFT analysis, six nsSNPs were identified as deleterious and reporting second and third nsSNPs as probably damaging and one as benign, respectively. From upstream analysis, rs138279736, rs201778935, rs369567630, and rs376038796 were found to be deleterious, probably damaging, and disease associated. ConSurf predicted conservation scores for four nsSNPs, and Project Hope suggested that all mutations could disrupt protein interactions. Furthermore, mCSM and DynaMut2 analyses indicated a decrease in ΔΔG stability for the mutants. GeneMANIA and STRING networks highlighted correlations with CD86 and CD80 genes. Finally, MD simulation revealed consistent fluctuation in RMSD and RMSF, consequently Rg, hydrogen bonds, and PCA in the mutant proteins compared with wild-type, which might alter the functional and structural stability of CTLA4 protein. The current comprehensive study shows how various nsSNPs in the CTLA4 gene can modify the structural and functional characteristics of the protein, potentially influencing the pathogenesis of diseases in humans. Further, experimental studies are needed to analyze the effect of these nsSNPs on the susceptibility of pathological phenotype populations.

Bisphenol S (BPS), a widely used substitute for Bisphenol A (BPA), is frequently detected in aquatic environments and has raised concerns due to its potential neurotoxic effects. Despite being marketed as a safer alternative, the long-term impacts of BPS on neural function and behaviour remain poorly understood. This study investigated whether embryonic exposure to environmentally relevant concentrations of BPS induces persistent neurobehavioural, neurochemical, and molecular alterations in adult zebrafish (Danio rerio). Embryos were exposed to an environmentally relevant concentration of BPS (30 µg/L) from 4 to 120 h post-fertilization (hpf) and subsequently reared in clean water until 6 months of age. Adult behavioural assessments revealed that BPS-exposed fish exhibited significant deficits in social affiliation, spending less time in the conspecific zone during group preference testing. However, shoaling behaviour and anxiety-like responses in the novel tank test, including swimming speed and zone preference, remained unaffected. Neurochemical analysis showed a significant reduction in brain dopamine levels, while serotonin (5-HT) and acetylcholine (ACh) levels were unchanged. Oxidative damage was corroborated by a significant elevation of brain lipid peroxidation (LPO) following embryonic BPS exposure. Molecular profiling of adult brain tissues revealed alterations in genes associated with oxidative stress (gpx1a), apoptosis (p53, bax, casp3), neuroinflammation (tnf-α, il1b, ngfb), and neurotransmission, particularly within serotonergic (slc6a4b, htr1d, htr2b) and cholinergic (chata) pathways. These findings indicate that embryonic BPS exposure leads to persistent neurochemical and transcriptional changes that selectively impair adult social behaviour without broadly affecting anxiety or locomotion. These observations underscore the potential neurodevelopmental toxicity of BPS and the urgent need to re-evaluate its safety in aquatic environments.