Reproductive Toxicity Research Articles

The mechanistic pathway induced by fenpropathrin toxicity: Oxidative stress, signaling pathway, and mitochondrial damage.

Fenpropathrin (FNP) is a kind of insecticide and acaricide known as pyrethroid. It is very effective, has a wide range of activities, and works quickly. Internationally, it is commonly considered the most powerful pyrethroid insecticide. Nevertheless, an increasing amount of data indicates a substantial link between Fenpropathrin and adverse effects on nontarget species, including liver toxicity, kidney toxicity, nerve damage, and reproductive toxicity. Oxidative stress plays a vital role in the toxicity of fenpropathrin, in addition to its mechanical mechanism. This study offers a thorough examination of the harmful effects of Fenpropathrin on oxidative and mitochondrial processes, as well as the signaling pathways involved in these effects. The significant impact of oxidative stress emphasizes the toxicity of Fenpropathrin.

Deoxynivalenol induces ovarian damage and uterine changes in prepubertal and adult mice

Deoxynivalenol (DON) is associated with reproductive toxicity in animals. The frequent contamination of cereal-based foods with DON and the high intake of these by children raises particular concern about the susceptibility of this subpopulation to adverse effects from this mycotoxin. However, age-related differences in the in vivo reproductive toxicity of DON have not been evaluated. Therefore, the effects of DON on serum follicle-stimulating hormone (FSH) levels, histology, and inflammatory and oxidative stress responses in the ovaries and uteruses of prepubertal and adult mice were investigated. Twenty female prepubertal Swiss mice (21 days old) and 20 young adult mice (65 days old) were fed a control diet or a diet containing 10 mg of DON/kg of feed for 15 days (prepubertal mice) and 28 days (adult mice). In the ovaries, DON induced an increase in the lesional score in both age groups. Ingestion of DON decreased FSH levels in prepubertal females, whereas an increase was observed in adult mice. In prepubertal mice, a reduction in the number of macrophages and increased levels of TNF-α were observed in the ovaries of the DON group, while in adult animals, an increase in the number of macrophages and higher levels of TNF-α were noted. The prepubertal animals showed edema in the uterine tissue and increased thickness of the uterine wall and endometrium. Exposure to DON led to an increase in type I collagen in the uteruses of adult mice, while in prepubertal mice, a decrease in type III collagen was observed. DON exposure also resulted in a decrease in FRAP levels and an increase in ABTS and lipid peroxidation in the uteruses of prepubertal mice. Taken together, the results indicate that the effects of DON on reproductive organs are age-specific, with toxicity established as early as the prepubertal period.

Safety concerns of paternal drug exposure on fertility, pregnancy and offspring: An analysis based on the FDA adverse event reporting system.

Growing evidence indicates that paternal condition significantly influences pregnancy outcomes and offspring health. However, assessing the safety of paternal drug exposure via randomized controlled trials poses ethical challenges, and relevant clinical studies consume a lot of resources to evaluate only a few drugs. Currently, safety data on paternal drug exposure are scarce. To investigate the impact of paternal drug exposure on fertility, pregnancy outcomes, and offspring health. Data from the FDA adverse event reporting system (FAERS) were analyzed (2010-2022). Disproportionality analyses were used to identify signals of each drug-adverse event pair associated with paternal drug exposure in a different hierarchical manner. Out of the 16,180,533 reports, 3210 were related to paternal exposure, encompassing 7808 concomitant adverse events. Drugs used to treat rheumatoid arthritis, cancer, and infections were primary sources of paternal exposure. Analysis identified 115 signals concerning reproductive health. Notably, the signals of diazepam-small for dates baby and finasteride-cryptorchidism were particularly significant (reporting odds ratio, ROR>800, N>10). Moreover, spontaneous abortion signals occur frequently in biologics for the treatment of immune inflammation; the use of immunosuppressive drugs was associated with the highest number of congenital anomalies, with the strongest signals for belatacept-skeletal dysplasia, and tacrolimus-talipes. Only mycophenolic acid, estrogen and imatinib have signals on male fertility. Anti-tumor agents had high numbers of each reproductive toxicity, with the highest values of trisomy 13 signals associated with etoposide and cisplatin. This is the first research to fully assess the safety of paternal exposure to the majority of medications in terms of reproduction. Clinical and scientific researchers should pay close attention to the list of risk medications included in this study, particularly the following association combinations: biologics used to treat inflammatory diseases-abortion, diazepam-small for date baby, finasteride-cryptorchidism, etoposide and cisplatin-13 trisomy.

Polyethylene Terephthalate Microplastic Exposure Induced Reproductive Toxicity Through Oxidative Stress and p38 Signaling Pathway Activation in Male Mice

Polyethylene terephthalate (PET) is a type of polymer plastic that is often used to make plastic bags, bottles, and clothes. However, the waste of such plastic products is decomposed into microplastics (MPs), which are plastic fragments smaller than 5 mm, by various external forces such as wind, UV radiation, mechanical wear, and biodegradation. PET MPs have been widely detected in the environment and human tissue samples; however, the toxicity and mechanism of PET MPs in mammals are still unclear. In this study, we investigated the male reproductive toxicity of PET MPs and their underlying mechanism. A total of 80 male mice were orally exposed to 0.01, 0.1, and 1 mg/d of PET MPs (with a diameter of 1 μm) for 42 days. The results showed that 1 μm PET MPs induced different degrees of pathological damage to testicular tissues, decreased sperm quality, and increased the apoptosis of spermatogenic cells via oxidative stress and p38 signaling pathway activation. To further illustrate and verify the mechanistic pathway, oxidative stress was antagonized using N-acetylcysteine (NAC), and the activation of the p38 signaling pathway was blocked using SB203580. The results revealed that the male reproductive injury effects after exposure to PET MPs were significantly ameliorated. Specifically, the testicular tissue lesions were relieved, the sperm quality improved, and the apoptosis of spermatogenic cells decreased. These results demonstrated that PET MP exposure induced male reproductive toxicity through oxidative stress and the p38 signaling pathway. This study provides new insights into the reproductive toxicity of MPs in males, as well as valuable references for public health protection strategies.

The key to 2,6-dichloro-1,4-benzoquinone reproductive toxicity and green tea detoxification: Covalent binding and competitive binding

Halobenzoquinones (HBQs) are ubiquitous disinfection by-products (DBPs) in chlorinated drinking water with various health risks including reproductive toxicity, while the potential mechanisms are still unclear. Although green tea exhibits common detoxifying properties, its ability to mitigate the toxicity of HBQs still needs to be further deepened and explored. This study attempted to investigate the possible mechanism of the most common HBQ, 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ) induced reproductive toxicity and elucidate the protective effect of green tea using a series of liquid chromatography-tandem mass spectrometry (LC-MS) approaches. Firstly, in vivo experiments showed that 2,6-DCBQ could induce testicular damage in male rats via significantly decreasing sperm-associated Leydig cells and seminiferous tubules. Then, in vitro incubation of 2,6-DCBQ with amino acids suggested that 2,6-DCBQ could bind to proteins via residues of cysteine or lysine and provided five additional modification patterns. Following, proteomics analysis revealed that at least 42 proteins were modified by 2,6-DCBQ, which were mainly enriched in the reproductive system. These results highlighted the significance of covalent protein modification in 2,6-DCBQ reproductive toxicity. Fortunately, we found that catechins (a class of major components of green tea) could competitively bind to 2,6-DCBQ in vivo and in vitro, reducing the amount and type of 2,6-DCBQ-protein adducts, thereby attenuating the reproductive system damage caused by 2,6-DCBQ. This study provides new insights into 2,6-DCBQ-induced reproductive system damage and reveals a new mechanism of green tea detoxification. Moreover, these findings offer potential strategies for alleviating the harmful impacts of environmental toxicants on human health.

Histone Methylation-Mediated Reproductive Toxicity to Consumer Product Chemicals in Caenorhabditis elegans: An Epigenetic Adverse Outcome Pathway (AOP).

The significance of histone methylation in epigenetic inheritance underscores its relevance to disease and the chronic effects of environmental chemicals. However, limited evidence of the causal relationships between chemically induced epigenetic changes and organismal-level effects hinders the application of epigenetic markers in ecotoxicological assessments. This study explored the contribution of repressive histone marks to reproductive toxicity induced by chemicals in consumer products in Caenorhabditis elegans, applying the adverse outcome pathway (AOP) framework. Triclosan (TCS) and tetrabromobisphenol A (TBBPA) exposures caused reproductive toxicity and altered histone methyltransferase (HMT) and histone demethylase (HDM) activities, increasing the level of trimethylation of H3K9 and H3K27. Notably, treatment with an H3K27-specific HMT inhibitor alleviated reproductive defects and the transcriptional response of genes related to vitellogenin, xenobiotic metabolism, and oxidative stress. Comparison of points of departure (PODs) based on calculated benchmark concentrations (BMCs) revealed the sensitivity of histone-modifying enzyme activities to these chemicals. Our findings suggest that the 'disturbance of HMT and HDM' can serve as the molecular initiating event (MIE) leading to reproductive toxicity in the epigenetic AOP for TCS and TBBPA. The study extended the biological applicability of these enzymes by identifying model species with analogous protein sequences and functions. This combined approach enhances the essentiality, empirical support, and taxonomic domain of applicability (tDOA), which are crucial considerations for ecotoxicological AOPs. Given the widespread use and environmental distribution of chemicals in consumer products, this study proposes histone-modifying enzyme activity as an effective screening tool for reproductive toxicants and emphasizes the integration of epigenetic mechanisms into a prospective ERA.

Study of combined multiple exposure and reproductive / developmental toxicity of 2-ethylhexanoic acid by screening method

Introduction. According to the normative and methodological documents of the Russian Federation, chemicals introduced into economic activities are subject to mandatory toxicological assessment and hygienic regulation. To substantiate the value of the hygienic standard of 2-ethylhexanoic acid, the production of which is planned in the country, additional test on its reproductive toxicity was required. The aim of the research was to determine the no-observed adverse effect levels of the 2-ethylhexanoic acid for maternal and reproductive toxicities in combined multiple exposure and the reproduction/developmental toxicity screening test (OECD 422). Materials and methods. The study was performed in accordance with the requirements of the OECD Test Guideline 422 «Combined repeated dose toxicity study with the reproduction/developmental toxicity screening test». Results. During the experiment no animal deaths or clinical symptoms of the toxic effect of 2-ethylhexanoic acid were observed at all tested doses (250, 500 and 1000 mg/kg b.w.). The assessment of behavioural responses using the open field method showed no differences in animals from experimental and control group. Histological examination indicated the acid at doses of 500 and 1000 mg/kg b.w. to cause significant changes in bladder (increased sclerosis in the submucosa), lungs (increased proportion of emphysematous altered parenchyma), adrenal gland (increased cell alterations and lipomatous inclusions), thyroid gland (increased loci of interfollicular tissue) in males and females’ rats. The total weight of offspring in the experimental groups was found to be statistically dose-dependent reduced on days 4 and 13 after birth compared with the control. Limitations. The study had no limitations. Conclusion. 2-Ethylhexanoic acid has no effect on the reproductive function in experimental animals. Developmental toxicity, expressed in a decrease in the total weight of offspring, was observed at the level of general toxic effects and is not specific. NOAELs were established at the level of 250 mg/kg b.w. for general toxic effect, > 1000 mg/kg b.w. for reprotoxic effect.

Assessing the chronic toxicity of climbazole to Daphnia magna: Physiological, biochemical, molecular, and reproductive perspectives

The widespread use of climbazole (CBZ) has led to its increased presence in aquatic environments, potentially threatening freshwater ecosystems. However, evidence regarding the harmful effects of CBZ on aquatic organisms remains limited. In this study, Daphnia magna was exposed to CBZ at concentrations of 0, 0.2, 20, and 200 μg/L for 21 days to evaluate its chronic toxicity through assessment of life-history traits, physiological parameters, biochemical analyses, and gene expression. The results indicated that CBZ exposure delayed the days to the first brood, reduced the frequency of molting per adult, decreased the offspring number at first brood, diminished the body length, and decreased both the total number of broods per female and the total number of offspring per female. Additionally, CBZ inhibited the swimming speed, filtration rate, and ingestion rate. Moreover, CBZ altered the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), while increasing malondialdehyde (MDA) levels. Gene expression analysis revealed varied responses in mRNA levels related to metabolic detoxification (cyp360a8, gst, and p-gp), digestive enzymes (α-amylase, α-esterase, and trypsin), energy (ak), oxygen transport (dhb), and reproduction (nvd, cyp314, ecr, vtg, and jhe) following CBZ exposure. These results indicate that the presence of CBZ in aquatic environments can induce toxicity by altering energy acquisition, supply, and metabolism; impairing metabolic detoxification pathways; eliciting oxidative stress; and causing reproductive toxicity in D. magna.

Ameliorative Effects of N-Acetyl Cysteine and Zinc Sulfate on Reproductive Dysfunction Induced by Short-Term Crude Oil Exposure in Male Wistar Rats

Background: Crude oil contamination by accidental or voluntary ingestion is prevalent in the Niger Delta region of Nigeria. One of the possible impacts of crude oil contamination is reproductive toxicity leading to infertility. The present study evaluated the potential protective effects of N-Acetyl Cysteine (NAC) and Zinc Sulfate (ZnSO4) in mitigating reproductive dysfunction caused by short-term Bonny Light Crude oil (BLCO) exposure in male Wistar rats. Materials and Methods: Fifty (50) male Wistar (180 – 200g) were used for the study. They were divided into ten (10) groups of five (5) animals each. Groups I and II served as the control and negative control and received distilled water and BLCO (600mg/kg) respectively while groups III to X served as the experimental groups and received NAC (100 and 200mg/kg) and ZnSO4 (0.5mg/kg and 1mg/kg) orally for three (3) weeks. Animals were euthanized, and blood and semen were collected for biochemical and seminal analysis. Results: The results of this current study show that BLCO exposure caused a disruption in reproductive functions in rats by decreasing reproductive hormones and semen quality parameters in Wistar rats. NAC and ZnSO4 administration significantly improved semen quality parameters by improving sperm count, sperm motility and morphology in experimental rats. Conclusion: Evidence from the present study suggests that NAC and ZnSO4 protected the testes, preventing reproductive alterations linked to BLCO exposure.

Physiologically based toxicokinetic and toxicodynamic (PBTK-TD) modelling of cis-bifenthrin in Carassius auratus and Xenopus laevis accounting for reproductive toxicity

Pyrethroid insecticides are a class of endocrine disruptors and are believed to exhibit reproductive toxicity to aquatic organisms. Pyrethroids are widely detected in aquatic environments and can accumulate in aquatic organisms, but studies on their accumulation and the associated reproductive toxicity in aquatic organisms are still limited. We utilized Carassius auratus and Xenopus laevis as models for fish and amphibians, respectively, and developed and validated a physiologically based toxicokinetic and toxicodynamic (PBTK-TD) model for adult fish and frogs exposed to typical pyrethroid pesticides cis-bifenthrin (cis-BF). The model includes the brain, kidney, liver, gonads, gills/lungs, well-perfused tissue, and poorly-perfused tissue, which are interconnected by blood circulation in the PBTK process. There are also dynamic relationships between target organ concentrations and reproductive-related endpoints in the TD process. Results showed that the PBTK sub-model accurately described and predicted the uptake, distribution, and disposition kinetics in fish and frogs. In fish, the kidney exhibited the fastest accumulation rate, while in frogs, the skin showed the fastest accumulation rate, followed by the kidney. Sensitivity analysis indicated that parameters such as blood flow and blood distribution coefficients had significant effects on chemical concentrations. A sigmoid Emax model was employed to describe the relationship between the reproductive toxicity effects of cis-BF and its dose-concentration variations. We found that testosterone (T) exhibited the highest correlation coefficient, suggesting that T could serve as an effective biomarker for cis-BF reproductive toxicity. The PBTK-TD model established in this study is beneficial for predicting the toxicological effects of pyrethroids in fish and amphibians.

VERMEER FCM: A tool integrating exposure and hazard modelling for chemicals migrating from food contact materials

A new tool, VERMEER FCM, was developed to support the risk assessment of single organic chemicals migrating from plastic food contact materials (FCM). The freely available tool is integrated into MERLIN-Expo and has been designed in line with Regulation (EU) No 10/2011 for plastic FCM. Overall, the tool consists of three modules that allow (i) to model the migration of chemicals into food, (ii) to predict toxicological endpoints relevant to risk assessment of FCM chemicals, and (iii) to automatically check whether the chemical of interest is included in Regulation (EU) No 10/2011. To apply the VERMEER FCM tool, users need to provide information regarding the chemical(s) of interest, the FCM, the food and other parameters (e.g. contact time and temperature). The three modules can be run either separately or in combination. Migration is predicted by a recently developed migration model, whereas hazard predictions for genotoxicity, subchronic toxicity, reproductive and developmental toxicity and carcinogenicity are provided by QSAR models selected from the publicly available VEGA HUB. The major novelty of the tool is that it combines information on hazard and exposure (i.e. migration) with regulatory information. Several case studies were performed to demonstrate the application of the tool.

Methodological approaches to the creation of a biological model of smoke in landscape fires

Introduction. Long-term smoke from landscape fires causes various health problems, primarily affecting the respiratory, cardiovascular, and nervous systems. To substantiate safe levels of exposure to smoke from landscape fires, it is necessary to create an adequate biological model for smoke that is close to natural conditions. The aim of the study is to develop and test methodological approaches to creating a biological model for smoke during landscape fires to substantiate safe levels of exposure. Materials and methods. Using the developed biological model, we studied the effects of smoke from landscape fires on white rats. We assessed the functional state of the central nervous system based on rat behaviour and EEG examination results, conducted a morphological study of the cerebral cortex and testes of white rats, and examined the offspring immediately after birth and at puberty. Results. We studied the biological response of white rats exposed to inhalation smoke from landscape fires for different durations. The main criterion indicators of health disorders in the central nervous and reproductive systems of animals were identified. Limitations. The study is limited by the lack of data on safe levels of exposure to smoke from landscape fires on the central nervous system and reproductive toxicity. Conclusion. Testing of the developed method allowed identifying the exposure load of carbon monoxide and ultrafine particles PM2.5, at which changes in the nervous and reproductive systems are minimal. A method for calculating safe levels of exposure for the central nervous and reproductive systems, as well as for the effect on offspring, is proposed. An algorithm for conducting research in studying the effect of smoke from landscape fires on the body has been developed.

Resmethrin disrupts mitochondria-associated membranes and activates endoplasmic reticulum stress, leading to proliferation inhibition in cultured mouse Leydig and Sertoli cells

Resmethrin, a pyrethroid pesticide used to control insects, is toxic to non-target organisms and other mammals. However, little is known about the reproductive toxicity of resmethrin in the testes, or its mechanism of toxicity. In this study, we investigated the testicular toxicity of resmethrin on mouse Leydig (TM3) and Sertoli (TM4) cells, focusing on the mitochondria and endoplasmic reticulum (ER). We found that resmethrin inhibited proliferation and cell cycle progression and disrupted mitochondrial membrane potential (MMP; ΔΨ) in TM3 and TM4 cells. In particular, resmethrin exposure significantly reduced the expression of mitochondria-associated membranes (MAMs) proteins, such as Vapb, Vdac, and Grp75, in both cell lines. Resmethrin also disrupts calcium homeostasis in the mitochondrial matrix and cytoplasm. In addition, resmethrin activates oxidative stress-mediated ER stress signals. Finally, we confirmed that 4-PBA, an ER stress inhibitor, restored the growth of TM3 and TM4 cells, which was decreased by resmethrin. Therefore, we confirmed that resmethrin hampered MAMs and activated ER stress, thus suppressing TM3 and TM4 cell proliferation.

Toxicological Effects and Mechanisms of 2,2',4,4'-Tetrabromodiphenyl Ether (BDE-47) on Marine Organisms.

2,2',4,4'-tetrabromodiphenyl ether (BDE-47) is a widely used brominated flame retardant belonging to persistent organic pollutants (POPs). After being released into the marine environment, BDE-47 can cause a range of toxic effects on marine organisms through bioaccumulation, biomagnification, and intergenerational transmission. These effects include lethality, impaired motility, photosynthetic toxicity, immune damage, liver toxicity, developmental impairments, and reproductive toxicity. This article reviews the latest research progress on the toxic effects and molecular mechanisms of BDE-47 mentioned above. The primary mechanisms underlying its toxicity include oxidative stress, DNA damage, cellular apoptosis, impaired metabolism, and activation of the MAPK signaling cascade.

Multi‐branched octopus‐like plasticizers with excellent plasticizing performance in poly(vinyl chloride)

AbstractThe development of alternatives is a priority issue for the plasticizer industry due to the reproductive toxicity and potential carcinogenicity of phthalate plasticizers. Herein we demonstrate the synthesis and characterization of multi‐branched octopus‐like plasticizers applied in poly(vinyl chloride) (PVC). The plasticizers were achieved through a straightforward one‐step esterification reaction, resulting in four polyol ester plasticizers (glyceryl tri‐n‐octanoate [GTOE], pentaerythritol tetra‐n‐octanoate [PQOE], xylitol penta‐n‐octanoate [XPOE], and mannitol hexa‐n‐octanoate [MHOE]). The multi‐branched structure enhances the interactions between plasticizers and PVC molecules leading to superior plasticizing properties, particularly mechanical properties, thermal stability, and migration resistance compared with commercial plasticizers di(2‐ethylhexyl) phthalate (DEHP), dioctyl terephthalate (DOTP), and acetyl tributyl citrate (ATBC). Concretely, the elongation at break of MHOE/PVC (825%) and PQOE/PVC (814.63%) was better than that of DEHP/PVC (670.02%), DOTP/PVC (490.62%) and ATBC/PVC (566.78%). The T5% of GTOE/PVC, PQOE/PVC, XPOE/PVC, and MHOE/PVC were 46.97, 67.24, 60.09 and 48.14°C higher than ATBC/PVC respectively. In the volatility resistance testing after 48 h, the weight loss of GTOE/PVC, PQOE/PVC, XPOE/PVC, and MHOE/PVC was 5.63%, 3.64%, 2.95%, and 8.88% respectively, which was far less than DEHP/PVC (15.58%), DOTP/PVC (11.83%) and ATBC/PVC (18.15%). Consequently, the obtained plasticizers demonstrate enhanced plasticizing efficiency, presenting promising alternatives to phthalate plasticizers and expanding the repertoire of choices within the plasticizer industry.

Sublethal concentration of λ-cyhalothrin inhibits insulin-like peptides and leads to reproductive toxicity in Chrysoperla sinica.

Insulin-like peptides (ILPs) act as crucial reproductive neuropeptides in insects, regulating insect reproduction through the insulin signaling pathway (ISP). Our previous studies have found that the sublethal concentrations (LC1 and LC10) of lambda-cyhalothrin (λCy) could induce severe reproductive toxicity in the lacewing, Chrysoperla sinica (Tjeder), but the toxicological mechanism remains unclear. This study discovered that λCy could inhibit CsILP transcription, leading to a decrease in insulin content and downregulation of C. sinica insulin receptor (CsInR) and C. sinica forkhead box O (CsFOXO) expression in ISP. Interference with CsILP expression resulted in downregulation of C. sinica vitellogenin (CsVg) and decreasing fecundity, while exogenous injection of bovine insulin promoted upregulation of CsVg expression and facilitated reproduction in female adults of C. sinica. Meanwhile, interference with FOXO of ILP downstream transcription factor could lead to downregulation of CsVg, hindering ovarian development and resulting in a decrease in egg production. However, exogenous injection of bovine insulin could remedy the effects caused by FOXO interference. In addition, ILP mediates juvenile hormone and 20-hydroxyecdysone biosynthesis by acting on their synthetic regulatory enzymes and influences the signal transduction of the 2 reproductive endocrine hormones, thereby regulating the reproductive endocrine environment in C. sinica. In conclusion, λCy inhibits CsILP expression, leading to disorder of ISP, leading to the reduced fecundity of C. sinica.

Taurine Protects against Silica Nanoparticle-Induced Apoptosis and Inflammatory Response via Inhibition of Oxidative Stress in Porcine Ovarian Granulosa Cells.

Silica nanoparticles (SNPs) induce reproductive toxicity through ROS production, which significantly limits their application. The protective effects of taurine (Tau) against SNP-induced reproductive toxicity remain unexplored. So this study aims to investigate the impact of Tau on SNP-induced porcine ovarian granulosa cell toxicity. In vitro, granulosa cells were exposed to SNPs combined with Tau. The localization of SNPs was determined by TEM. Cell viability was examined by CCK-8 assay. ROS levels were measured by CLSM and FCM. SOD and CAT levels were evaluated using ELISA and qPCR. Cell apoptosis was detected by FCM, and pro-inflammatory cytokine transcription levels were measured by qPCR. The results showed that SNPs significantly decreased cell viability, while increased cell apoptosis and ROS levels. Moreover, SOD and CAT were decreased, while IFN-α, IFN-β, IL-1β, and IL-6 were increased after SNP exposures. Tau significantly decreased intracellular ROS, while it increased SOD and CAT compared to SNPs alone. Additionally, Tau exhibited anti-inflammatory effects and inhibited cell apoptosis. On the whole, these findings suggest that Tau mitigates SNP-induced cytotoxicity by reducing oxidative stress, inflammatory response, and cell apoptosis. Tau may be an effective strategy to alleviate SNP-induced toxicity and holds promising application prospects in the animal husbandry and veterinary industry.

Toxicity of parental co-exposure of microplastic and bisphenol compounds on adult zebrafish: Multi-omics investigations on offspring

In recent years, the widespread use of bisphenol compounds and microplastics (MP) have attracted attention due to their harmful effects. Here, individual and combined effects of MP and bisphenol compounds, were assessed on adult zebrafish after co-exposure of bisphenol A (BPA) or bisphenol S (BPS) and 25 μm polyethylene MP. Impacts on their offspring (the F1 generation) were also investigated. The reproductive toxicity in adult zebrafish impacted exerted by bisphenol compounds were aggravated by the co-presence of MP. Transcriptomics and metabolomics further showed single or co-exposure of bisphenol compounds and MP could together regulate apoptosis, calcium signaling pathway and glycerophospholipid signaling pathways. Our results also showed the different toxicity mechanisms on transcriptional and metabolic profiles in the combination effects of bisphenol compounds and MP. The co-exposure of BPA and MP predominantly influenced neurotoxicity via the MAPK signaling pathway and voltage-dependent calcium channels, whereas the co-exposure of BPS and MP principally affected visual development through phototransduction and retinol metabolism. The co-exposure of BPA and MP, as well as BPS and MP, specifically regulate lipid metabolism and carbohydrate metabolism in zebrafish offspring, respectively. Overall, this study provided a deep understanding of the toxicity differences between co-exposure and single exposure of bisphenol compound and MP in zebrafish, as well as the transgenerational effects and potential molecular mechanisms of bisphenol compounds and MP in zebrafish offspring.

Natural pesticide, Azadirachta indica A. Juss. (Neem), disrupted reproductive parameters of male rats

Ethnopharmacological relevanceNeem (Azadirachta indica A. Juss.) is native to India and belongs to the Meliaceae family. It has been used for centuries in Eastern medicine, and more recently, as a natural pesticide. Although the use of bioinsecticides is supported by organic food production, further research is needed on each formulation, particularly on their effects on organisms. Aim of the studyThis study evaluated the reproductive toxicity of an aqueous extract of neem leaves in male Wistar rats of reproductive age after eight days of exposure. Materials and methodsFor this study, 20 rats were divided into four groups of five animals each and treated with different concentrations: Group 1 received 10,000 ppm, Group 2 received 7500 ppm, Group 3 received 5000 ppm, and Group 4 served as the control, received distilled water. The animals were observed for eight days for any clinical signs of toxicity. Semen quality, including sperm motility and viability, was analyzed. ResultsNo significant differences in physiological changes were observed between treatments. However, sperm motility and viability were affected in a concentration-dependent manner, with the group that received the highest dose exhibiting inviable spermatozoa. ConclusionThe data suggested that the administered doses had low toxicity. Nevertheless, concerns regarding reproductive toxicity remain because motility and sperm viability are negatively affected at the highest dose. Although bioinsecticides are widely used in organic food production, further research on each formulation, particularly regarding their long-term effects on organisms, is required.

Epigenetic Modifications Are Involved in Transgenerational Inheritance of Cadmium Reproductive Toxicity in Mouse Oocytes

Maternal cadmium exposure during pregnancy has been demonstrated to have detrimental effects on offspring development. However, the impact of maternal cadmium exposure on offspring oocytes remains largely unknown, and the underlying mechanisms are not fully understood. In this study, we found that maternal cadmium exposure during pregnancy resulted in selective alteration in epigenetic modifications of mouse oocytes in offspring, including a decrease in H3K4me2 and H4K12ac, as well as an increase in DNA methylation of H19. Although ROS levels and mitochondrial activity remain at normal levels, the DNA damage marker γH2AX was significantly increased and the DNA repair marker DNA-PKcs was remarkably decreased in offspring oocytes from maternal cadmium exposure. These alterations are responsible for the decrease in the quality of mouse oocytes in offspring induced by maternal cadmium exposure. As a result, the meiotic maturation of oocytes and subsequent early embryonic development are influenced by maternal cadmium exposure. RNA-seq results showed that maternal cadmium exposure elicits modifications in the expression of genes associated with metabolism, signal transduction, and endocrine regulation in offspring ovaries, which also contribute to the disorders of oocyte maturation and failures in early embryonic development. Our research provides direct evidence of transgenerational epigenetic inheritance of cadmium reproductive toxicity in mouse germ cells.