Disruption Of Development Research Articles

Neuroradiologic, clinic and genetic characterization of cerebellar heterotopia: a pediatric multicentric study.

Background and purpose:Cerebellar heterotopia (CH) is a neuroradiological abnormality poorly reported and investigated in the literature. It can be observed as an isolated finding, but it has been mainly reported in the context of cerebellar dysgenesis and in syndromic conditions. The aim of this study is to provide a comprehensive neuroradiological, clinical, and genetic characterization of a cohort of pediatric patients with cerebellar heterotopia.Materials and methods:Patients with a diagnosis of CH were systematically selected from the neuroimaging databases of the four Italian Centers participating in this retrospective study. For each patient, information regarding demographic, clinical, genetic and neuroradiological data were collected.Results:Thirty-two pediatric patients were recruited and subdivided into two groups: patients with isolated CH and/or cerebellar malformations (n= 18) and patients with CH associated with cerebral malformations (n=14). Isolated CH consistently showed a peripheral subcortical localization in the inferior portion of cerebellar hemispheres, with either unilateral or bilateral distribution. Ten patients belonging to the second group had a diagnosis of CHARGE syndrome, and their nodules of CH were mainly but not exclusively bilateral, symmetric, located in the peripheral subcortical zone and in the inferior portion of the cerebellar hemispheres; the remaining 4 patients of the second group, showed either bilateral or unilateral CH, located in both peripheral cortex and deep white matter and in the superior and inferior portions of cerebellum. Patients with isolated CH showed high prevalence of language development delay; neurodevelopmental disorders were the most represented clinical diagnoses. Recurring features were behavioral problems and motor difficulties. A conclusive genetic diagnosis was found in 18/32 patients.Conclusions:We found distinctive neuroradiological patterns of CH. Genetic results raise the possibility of a correlation between cerebellar morphological and functional developmental disruption, underscoring the importance of CH detection and reporting to orient the diagnostic path.Abbreviations CH Cerebellar heterotopia; MRI Magnetic resonance imaging; CC Corpus callosum; ASD autism spectrum disorder; IVH inferior vermian hypoplasia.

Toxoplasma gondii infection misdirects placental trophoblast lineage specification.

Pregnancy is a critical point of vulnerability to infection and other insults that could compromise proper fetal development. The placenta acts as a protective and nutrient-permeable barrier to most infectious agents, but a few are capable of bypassing its defenses. Remarkably little is known about how exposure to these select pathogens might impact ongoing placental development. Here we demonstrate that Toxoplasma gondii entirely misdirects the developmental program of trophoblast stem cells. Infection of progenitor cytotrophoblasts prevents fusion and differentiation to infection-resistant syncytiotrophoblast. Rather, T. gondii elicits a unique transcriptional identity that polarizes cytotrophoblasts to the infection-permissive extravillous trophoblast fate. Strong evidence of developmental disruption is found in multiple orthogonal models, including trophoblast stem cells, trophoblast organoids, and chorionic villi. Manipulation of cell fate by the parasite is most dramatic in trophoblast organoids, where we see robust outgrowth of HLA-G(+) extravillous trophoblasts. Collectively, these data show that Toxoplasma antagonizes differentiation of an infection-resistant cell type by inducing formation of an infection-permissive cell type, therefore potentiating its own transmission to the fetus.

Distinct transcriptional profiles in rat thyroid glands after developmental exposure to three in vitro thyroperoxidase inhibiting chemicals

Thyroperoxidase (TPO) is central in thyroid hormone (TH) synthesis and inhibition can lead to TH deficiency. Many chemicals can inhibit TPO activity in vitro, but how this may manifest in the developing thyroid gland at the molecular level is unclear. Here, we characterized the thyroid gland transcriptome of male rats developmentally exposed to the in vitro TPO-inhibitors amitrole, 2-mercaptobenzimidazole (MBI), or cyanamide by use of Bulk-RNA-Barcoding (BRB) and sequencing. Amitrole exposure caused TH deficiency and 149 differentially expressed genes in the thyroid gland. The effects indicated an activated and growing thyroid gland. MBI caused intermittent changes to serum TH concentrations in a previous study and this was accompanied by 60 differentially expressed genes in the present study. More than half of these were also affected by amitrole, indicating that they could be early effect biomarkers of developmental TH system disruption due to TPO inhibition. Further work to validate the signature is needed, including assessment of substance independency and applicability domain.

Bisphenol A Disrupts Ribosome Function during Ovarian Development of Mice.

This study examines the impact of Bisphenol A (BPA), a prevalent environmental estrogenic toxicant, on the ovarian development of mice. Mice were exposed to varying BPA doses from in utero to postnatal stages, up to weaning (day 21, PND 21) and puberty (day 45, PND 45). The BPA content in the serum of the offspring mice on PND 45 was higher than that of the mice sacrificed at PND 21. However, the ovary organ index of the mice of PND 21 was significantly increased, and the ovarian structure was damaged when exposed to BPA. In contrast, the mice with PND 45 did not show apparent ovarian lesions. On the other hand, granulosa cell apoptosis was detected in both PND 21 and PND 45 mice ovaries, and ERβ was increased under the influence of BPA. Transcriptomic analysis revealed BPA's significant impact on ribosomal gene expression, marked downregulation of Rpl21 and Rpsa, and upregulation of Rps2 in both age groups. These transcriptomic alterations were further corroborated by real-time PCR, highlighting a dose-dependent effect of BPA on Rps2. Our findings confirm BPA's detrimental effects on ovarian health, with more pronounced damage in younger mice, suggesting heightened vulnerability in this group. The study underscores ribosomes as critical targets in BPA-induced ovarian developmental disruptions.

Study of Ontogenetic Structure and Density of the Coenopopulation of Hedysarum atropatanum Bunge ex Boiss. Flora of Daridag

The article presents findings from a study of the demographic structure and density of the population of the species Hedysarum atropatanum Bunge ex Boiss., which is widely distributed in the Daridag area. A total of ten ontogenetic states (seed, seedling, juvenile, immature, virginile, young generative, middle aged generative, aged generative, subsenile and senile) of the H. atropatanum species were observed. The processes of ontogenesis, which can be classified as normal, fast, or slow, were identified as the primary mechanisms driving species evolution. Additionally, instances of developmental disruptions, rejuvenation, and the manifestations of aging were observed. The majority of individuals belonging to the species H. atropatanum exhibit a normal to rapid growth rate. It has been observed that the process of ontogenesis is slower in areas with high plant density. It was determined that the secondary quiescence period does not manifest during the initial stages of development; rather, it becomes feasible only after the individuals have reached the virginal state. It has not been observed that immature individuals bypass the virginal state and immediately transition to mature generative plants. The vitality status of the individuals was determined based on a comprehensive analysis of multiple morphological traits, including the height of the specimens, the number of shoots, the number of flower carriers, the length of the leaves, the size of the leaves, and the number of flowers in the flower group. Following the statistical processing of the data, three classes of vitality were identified. A study revealed that individuals of the second vitality level of the H. atropatanumspecies are more prevalent in the coenopopulation. The optimal habitats of the H. atropatanum s

Developmental disruption of the mitochondrial fission gene drp-1 extends the longevity of daf-2 insulin/IGF-1 receptor mutant.

The dynamic nature of the mitochondrial network is regulated by mitochondrial fission and fusion, allowing for re-organization of mitochondria to adapt to the cell's ever-changing needs. As organisms age, mitochondrial fission and fusion become dysregulated and mitochondrial networks become increasingly fragmented. Modulation of mitochondrial dynamics has been shown to affect longevity in fungi, yeast, Drosophila and C. elegans. Disruption of the mitochondrial fission gene drp-1 drastically increases the already long lifespan of daf-2 insulin/IGF-1 signaling (IIS) mutants. In this work, we determined the conditions required for drp-1 disruption to extend daf-2 longevity and explored the molecular mechanisms involved. We found that knockdown of drp-1 during development is sufficient to extend daf-2 lifespan, while tissue-specific knockdown of drp-1 in neurons, intestine or muscle failed to increase daf-2 longevity. Disruption of other genes involved in mitochondrial fission also increased daf-2 lifespan as did treatment with RNA interference clones that decrease mitochondrial fragmentation. In exploring potential mechanisms involved, we found that deletion of drp-1 increases resistance to chronic stresses. In addition, we found that disruption of drp-1 increased mitochondrial and peroxisomal connectedness in daf-2 worms, increased oxidative phosphorylation and ATP levels, and increased mitophagy in daf-2 worms, but did not affect their ROS levels, food consumption or mitochondrial membrane potential. Disruption of mitophagy through RNA interference targeting pink-1 decreased the lifespan of daf-2;drp-1 worms suggesting that increased mitophagy contributes to their extended lifespan. Overall, this work defined the conditions under which drp-1 disruption increases daf-2 lifespan and has identified multiple changes in daf-2;drp-1 mutants that may contribute to their lifespan extension.

Surgical exposure of turner’s tooth and CBCT representation of inverted tooth: A case report

Enamel defects related to it’s thickness and quality are called hypoplasia, and they arise from disturbances in the enamel matrix development process. The possible developmental disruptions, which can range from mild changes in enamel mineralization to severe sequestration of the tooth germ, dilations of the crown or root, crown or root duplication, and complete or partial arrest of root formation, are explained by the topographic relationship between the primary tooth and the developing permanent tooth germ. Enamel in Turner's hypoplastic kinds might be shiny, rough, or pitted . It is extremely uncommon for permanent central incisor impaction and inversion to result from trauma, odontomas, and neighboring supernumerary teeth. Root development is restricted when incisors are displaced or impacted in the opposite direction. Dental radiographs and CBCT are used to assess the presence or absence of enamel thickening and inversion. This information is used not only for diagnosis but also to build the best possible treatment plan. Hence a case is presented of Turner’s hypoplasia and maxillary lateral incisor inversion in a 9 yr old female. MESH- Turner’s Hypoplasia, Tooth inversion, CBCT, RVG

Environmental presence and toxicological outcomes of the herbicide pendimethalin in teleost fish.

Herbicides are often detected in aquatic ecosystems due to residential and agricultural applications and can harm aquatic organisms once deposited into water systems. Pendimethalin is part of the dinitroaniline chemical family and is applied to crops like corn, legumes, potatoes, and soybeans. The potential toxicity of pendimethalin to aquatic species is understudied compared to other widely studied herbicides, like atrazine and glyphosate. The objectives of this review were to (1) collate information on sub-lethal responses to pendimethalin exposure in fish, (2) evaluate how exposure studies relate to environmental concentrations, and (3) identify putative bioindicators for exposure studies. Overall, studies reporting pendimethalin in water systems worldwide indicate a range of 100-300 ng/L, but levels have been reported as high as ~15 µg/g in sediment. In teleost fish, studies demonstrate developmental toxicity, immunotoxicity, and behavioral disruptions. The strongest evidence for pendimethalin-induced toxicity involves oxidative stress, although studies often test toxicity at higher concentrations than environmentally relevant levels. Using the Comparative Toxicogenomics Database, pathway analysis reveals linkages to neurotoxicity and mechanisms of neurodegeneration like "Ubiquitin Dependent Protein Degradation", "Microtubule Cytoskeleton", "Protein Oxidation and Aggregation in Aging", and "Parkinson's Disease". Other prominent pathways included those related to mTOR signaling and reproduction. Thus, two potential mechanisms underlying pendimethalin-induced toxicity in fish include the neural and reproductive systems. This review synthesizes current data regarding environmental fate and ecotoxicology of pendimethalin in teleost fish and points to some putative physiological and molecular responses that may be beneficial for assessing toxicity of the herbicide in future investigations.

Trace elements alone or in mixtures associated with unconventional natural gas exploitation affect rat fetal steroidogenesis and testicular development in vitro

Biomonitoring studies have shown that pregnant women living in regions of unconventional natural gas (UNG) exploitation have higher levels of trace elements. Whether developmental endocrine disruption can be expected at these exposure levels during pregnancy is unclear. In this study, we aimed to test the impact of five trace elements alone or in mixtures using in vitro cell- and tissue-based assays relevant to endocrine disruption and development. Manganese, aluminum, strontium, barium, and cobalt were tested at concentrations including those representatives of human fetal exposure. Using transactivation assays, none of the tested elements nor their mixture altered the human estrogen receptor 1 or androgen receptor genomic signalling. In the rat fetal testis assay, an organ culture system, cobalt (5 μg/l), barium (500 μg/l) and strontium (500 μg/l) significantly increased testosterone secretion. Cobalt and strontium were associated with hyperplasia and/or hypertrophy of fetal Leydig cells. Mixing the five elements at concentrations where none had an effect individually stimulated testosterone secretion by the rat fetal testis paralleled by the significant increase of 3β-hydroxysteroid dehydrogenase protein level in comparison to the vehicle control. The mechanisms involved may be specific to the fetal testis as no effect was observed in the steroidogenic H295R cells. Our data suggest that some trace elements in mixture at concentrations representative of human fetal exposure can impact testis development and function. This study highlights the potential risk posed by UNG operations, especially for the most vulnerable populations, pregnant individuals, and their fetus.

Developmental Disruption of Mef2c in Medial Ganglionic Eminence–Derived Cortical Inhibitory Interneurons Impairs Cellular and Circuit Function

BackgroundMEF2C is strongly linked to various neurodevelopmental disorders including autism, intellectual disability, schizophrenia, and attention-deficit/hyperactivity disorder. Mice that constitutively lack 1 copy of Mef2c or selectively lack both copies of Mef2c in cortical excitatory neurons display a variety of behavioral phenotypes associated with neurodevelopmental disorders. The MEF2C protein is a transcription factor necessary for cellular development and synaptic modulation of excitatory neurons. MEF2C is also expressed in a subset of cortical GABAergic (gamma-aminobutyric acidergic) inhibitory neurons, but its function in those cell types remains largely unknown. MethodsUsing conditional deletions of the Mef2c gene in mice, we investigated the role of MEF2C in parvalbumin-expressing interneurons (PV-INs), the largest subpopulation of cortical GABAergic cells, at 2 developmental time points. We performed slice electrophysiology, in vivo recordings, and behavior assays to test how embryonic and late postnatal loss of MEF2C from GABAergic INs impacts their survival and maturation and alters brain function and behavior. ResultsLoss of MEF2C from PV-INs during embryonic, but not late postnatal, development resulted in reduced PV-IN number and failure of PV-INs to molecularly and synaptically mature. In association with these deficits, early loss of MEF2C in GABAergic INs led to abnormal cortical network activity, hyperactive and stereotypic behavior, and impaired cognitive and social behavior. ConclusionsMEF2C expression is critical for the development of cortical GABAergic INs, particularly PV-INs. Embryonic loss of function of MEF2C mediates dysfunction of GABAergic INs, leading to altered in vivo patterns of cortical activity and behavioral phenotypes associated with neurodevelopmental disorders.

Musculoskeletal and tendinous details of selected anomalies in the locomotor system of anurans.

Previous studies on anuran anomalies predominantly examine isolated cases or focus on external and skeletal features. Our study analyzes a comprehensive sample collected from 1991 to 2017, examining the muscle-tendon system in 24 anuran species across adult, juvenile, and metamorphic stages. This extensive sample size allows us to investigate consistent anomaly patterns across different developmental stages and anuran families, exploring potential common developmental or genetic factors. Our detailed anatomical examination, encompassing musculature, tendons, and skeletal structures, revealed that 21% of the specimens displayed anomalies, a noteworthy finding considering the extensive sample size and duration of the studied sample. Of these anomalies, 17% affected the locomotor system, predominantly in the upper limbs. Key anomalies included, forelimbs and hindlimbs brachydactyly, rotation in forelimbs, partial kyphotic lordosis, and scoliosis. Notably, the digit 4 in the forelimbs and digits 4 and 5 in the hindlimbs were particularly susceptible to teratogenic effects, indicating possible prolonged exposure during development. Our study also uncovered combinations of anomalies and identified a phenotype similar to Poland syndrome. The findings validate the "Logic of Monsters" (LoMo theory) by Alberch, although the name itself may not be deemed appropriate, showing that developmental disruptions in tetrapods are not random but follow distinct sequences and patterns. The name, while unfortunate, accurately reflects the unusual nature of these developmental anomalies. This contributes to the evolving "Evo-Devo-Path" framework, highlighting the study's importance in understanding developmental disruptions in tetrapods.

Knockdown of Lhx6 during embryonic development results in neurophysiological alterations and behavioral deficits analogous to schizophrenia in adult rats

A decreased expression of specific interneuron subtypes, containing either the calcium binding protein parvalbumin (PV) or the neurotransmitter somatostatin (SST), are observed in the cortex and hippocampus of both patients with schizophrenia and rodent models used to study the disorder. Moreover, preclinical studies suggest that this loss of inhibitory function is a key pathological mechanism underlying the symptoms of schizophrenia. Interestingly, decreased expression of Lhx6, a key transcriptional regulator specific to the development and migration of PV and SST interneurons, is seen in human postmortem studies and following multiple developmental disruptions used to model schizophrenia preclinically. These results suggest that disruptions in interneuron development in utero may contribute to the pathology of the disorder. To recapitulate decreased Lhx6 expression during development, we used in utero electroporation to introduce an Lhx6 shRNA plasmid and knockdown Lhx6 expression in the brains of rats on gestational day 17. We then examined schizophrenia-like neurophysiological and behavioral alterations in the offspring once they reached adulthood. In utero Lhx6 knockdown resulted in increased ventral tegmental area (VTA) dopamine neuron population activity and a sex-specific increase in locomotor response to a psychotomimetic, consistent with positive symptomology of schizophrenia. However, Lhx6 knockdown had no effect on social interaction or spatial working memory, suggesting behaviors associated with negative and cognitive symptom domains were unaffected. These results suggest that knockdown of Lhx6 during development results in neurophysiological and behavioral alterations consistent with the positive symptom domain of schizophrenia in adult rats.

Integrated Pest Management Precision: Harnessing the Joint Influence of Entomopathogenic Fungi, Nematodes, and Chlorantraniliprole for Targeted Control of Fall Armyworm (Spodoptera Frugiperda)

Background: The Spodoptera frugiperda, commonly known as the fall armyworm (FAW), is a significant pest impacting agricultural productivity worldwide. Originating from tropical and subtropical regions, FAW has shown a high capacity for migration and destruction across a wide variety of crops. Integrated Pest Management (IPM) strategies offer sustainable approaches to managing pest populations, minimizing environmental impact, and reducing reliance on chemical insecticides. Objective: This study aimed to evaluate the efficacy of combining biological control agents, specifically Heterorhabditis bacteriophora (Hb) and Beauveria bassiana (Bb), with the chemical insecticide chlorantraniliprole (Ch) against third and fifth instar larvae of S. frugiperda. The study sought to determine the potential synergistic effects of these combinations on larval mortality and developmental disruption. Methods: The research encompassed laboratory bioassays, greenhouse, and field trials to assess the impact of the biocontrol agents and chlorantraniliprole, both individually and in combination, on FAW larval mortality and development. Larval populations of S. frugiperda were collected and reared under controlled conditions. Treatments applied included Hb, Bb, Ch, Hb+Bb, Hb+Ch, Bb+Ch, and Hb+Bb+Ch. Mortality rates were recorded at 3, 5, and 7 days post-treatment, while developmental parameters were assessed through pupation rates, adult emergence, and egg eclosion percentages. Results: The combined application of Hb, Bb, and Ch significantly increased mortality rates in both the third and fifth instar larvae compared to individual treatments, with the highest mortality observed in the Hb+Bb+Ch group (100% by day 7). Developmental disruptions were also noted, including reduced pupation rates, adult emergence, and egg eclosion, particularly in treatments involving the combined use of biocontrol agents and chlorantraniliprole. Statistical analysis confirmed the significance of these findings (P<0.01). Conclusion: The integration of Hb, Bb, and Ch presents a viable IPM strategy for effectively managing S. frugiperda populations. This combination not only enhances larval mortality but also disrupts developmental stages, offering a potential reduction in FAW infestation levels and associated crop damages. These results underscore the importance of adopting sustainable pest management practices that leverage synergistic effects between biological and chemical agents.

Developmental and molecular contributions to contextual fear memory emergence in mice

Cognitive impairment is a common phenotype of neurodevelopmental disorders, but how these deficits arise remains elusive. Determining the onset of discrete cognitive capabilities facilitates studies in probing mechanisms underlying their emergence. The present study analyzed the emergence of contextual fear memory persistence (7-day memory retention) and remote memory (30-day memory retention). There was a rapid transition from postnatal day (P) 20 to P21, in which memory persistence emerged in C57Bl/6 J male and female mice. Remote memory was present at P23, but expression was not robust compared to pubertal and adult mice. Previous studies reported that following deletion of the MET receptor tyrosine kinase (MET), there are fear memory deficits in adult mice and the timing of critical period plasticity is altered in the developing visual cortex, positioning MET as a regulator for onset of contextual fear memory. Sustaining Met past the normal window of peak cortical expression or deleting Met, however, did not alter the timing of emergence of persistence or remote memory capabilities during development. Fear memory in young adults, however, was disrupted. Remarkably, compared to homecage controls, the number of FOS-expressing infragranular neurons in medial prefrontal cortex (mPFC) did not increase from contextual memory formation recall of fear conditioning at P35 but exhibited enhanced activation at P90 in male and female mice. Additionally, MET-expressing neurons were preferentially recruited at P90 compared to P35 during fear memory expression. The studies demonstrate a developmental profile of contextual fear memory capabilities. Further, developmental disruption of Met leads to a delayed functional deficit that arises in young adulthood, correlated with an increase of mPFC neuron activation during fear memory recall.

Behavioral Profiling of Zebrafish (Danio rerio) Larvae: Activity, Anxiety, Avoidance, and Startle Response.

Apart from morphological, biochemical, and genetic alterations induced by teratogen compounds, there is an increased interest in characterizing behavioral alterations. Behavior is a sensitive parameter that can provide information regarding developmental disruptions non-invasively. Behavioral disturbances interfere with animals' capacity to cope with the environment, having an impact on the organism's life. Hereby, behavioral assays consisting of recording larvae in multi-well plates, Petri dishes, or cuvettes and video analysis using adequate software, allowing teratogen screening of behavior, are proposed. Examples of how to evaluate locomotor, anxiety-like and avoidance-like behaviors, and the integrity of sensory-motor functions and learning are discussed in this chapter.

Effects of Microplastics on Living Organisms and their Trophic Transfer: An Ecotoxicological Review

Plastic is used by individuals within many different fields, including the automotive, packaging, cosmetics, textile and apparel, agricultural and fisheries sector and industries. Nevertheless, it has become a hazard to our ecosystem due to its extended degradation and decadences in nature, unceasing rise in manufacture and consumption with the increasing human population. Microplastics (MPs) can enter in both soil and aquatic environments through a variety of channels, including surface runoff, storm water runoff, river flow, and wastewater discharge. As a possible hazard to aquatic life, the existence and consumption of MPs has drawn significant attention from throughout the world. These tiny plastic particles absorb various substances and emit harmful additives, serving as sinks for dangerous substances and enhancing their bioavailability, toxicity, and movement. Additionally, the trophic transfer or bioaccumulation of MPs in a variety of aquatic creatures poses a significant concern. MPs have the potential to seriously harm aquatic life, including reduced eating efficiency, physical side effects, impaired gill function, oxidative stress, neurological damage, suppression of immunity and developmental disruption.

Fetal Alcohol Spectrum Disorders and Inadequacy of Care: Importance of Raising Awareness in Clinical Practice.

Prenatal alcohol exposure is one of the major avoidable causes of developmental disruption and health abnormalities in children. Fetal alcohol spectrum disorders (FASDs), a significant consequence of prenatal alcohol exposure, have gained more attention recently. This review aims to provide a narrative approach to the scientific literature on the history, clinical presentation, diagnosis, and management of FASDs. A literature search in PubMed, ScienceDirect, and Google Scholar online databases was conducted. The dates of publications ranged from 2000 to 2023. FASD presentations tend to persist into adulthood, which, combined with environmental factors, potentially lead to secondary psychosocial problems and disabilities. This review covers different aspects of FASDs regarding the concept of the umbrella term and public health, somatic, and psychiatric perspectives. FASD management remains an obstacle to health professionals, and mental health problems are underestimated. Its management involves a multi-disciplinary team, which varies according to the patient's individual needs. FASD diagnosis and management have not been sufficiently established and tailored. Stigma, cultural contexts, knowledge gaps, and the heterogeneity of clinical manifestations are significant barriers to an accurate diagnostic process. Further development of early interventions and the elaboration of complex treatment approaches are needed.

Effect of environmental level of methomyl on hatching, morphology, immunity and development related genes expression in zebrafish (Danio rerio) embryo

The extensive use of carbamate pesticides has led to a range of environmental and health problems, such as surface and groundwater contamination, and endocrine disorders in organisms. In this study, we focused on examining the effects of toxic exposure to the carbamate pesticide methomyl on the hatching, morphology, immunity and developmental gene expression levels in zebrafish embryos. Four concentrations of methomyl (0, 2, 20, and 200 μg/L) were administered to zebrafish embryos for a period of 96 h. The study found that exposure to methomyl accelerated the hatching process of zebrafish embryos, with the strongest effect recorded at the concentration of 2 μg/L. Methomyl exposure also trigged significantly reductions in heart rate and caused abnormalities in larvae morphology, and it also stimulated the synthesis and release of several inflammatory factors such as IL-1β, IL-6, TNF-α and INF-α, lowered the IgM contents, ultimately enhancing inflammatory response and interfering with immune function. All of these showed the significant effects on exposure time, concentration and their interaction (Time × Concentration). Furthermore, the body length of zebrafish exposed to methomyl for 96 h was significantly shorter, particularly at higher concentrations (200 μg/L). Methomyl also affected the expression levels of genes associated with development (down-regulated igf1, bmp2b, vasa, dazl and piwi genes), demonstrating strong developmental toxicity and disruption of the endocrine system, with the most observed at the concentration of 200 μg/L and 96 h exposure to methomyl. The results of this study provide valuable reference information on the potential damage of methomyl concentrations in the environment on fish embryo development, while also supplementing present research on the immunotoxicity of methomyl.

Delayed closure of the anterior fontanelle in Iron Age children from Zaghunluq, northwestern China.

Delayed closure of the anterior fontanelle is often associated with various disorders. However, the phenomenon might be a normal variation. In this study, the anterior fontanelle was investigated in children from the Iron Age Zaghunluq cemetery in Xinjiang, northwestern China. Age at death was estimated by tooth development/eruption in the children. The anterior fontanelle was visually assessed for delayed fusion. Three out of nine children aged between 3-6 years old from the cemetery had signs of open anterior fontanelle. However, there were no signs of craniofacial pathology or developmental disruption. Delayed closure of the anterior fontanelle might have been a norm in the Iron Age Zaghunluq population. However, it is impossible to determine the reasons behind the high prevalence of delayed AF closure at Zaghunluq. Additional studies are warranted to determine whether this phenomenon is population specific, or diet specific, or just an individual variation.

In ovo exposure of F-ions and organo-fluoride insecticide (Bifenthrin) cause developmental anomalies of eye in chick embryos

ObjectiveThe developmental abnormalities of the in-ovo exposure of Fluoride ions (F-ions) and Bifenthrin (BF) on the embryonic chick eye were investigated. Materials and methods165 fresh fertilized eggs of zero day and 40–50 g weight were divided into three groups (55 eggs each) on the basis of inter-vitelline treatment of eggs on zero day of study: 1) Control group (CG); 0.1 ml of 5 % DMSO aqueous solution 2),3) Fluoride group (FG), and Bifenthrin group (BFG); 0.01 mg/kg F-ions (from NaF) and 0.01 mg/kg BF in 0.1 ml of 5 % DMSO aqueous solution respectively. After incubation for 14 days at 37 ± 0.5 °C embryos were externalized. Eyes of each embryo were removed for micro-anatomical, micrometric and histopathological studies. ResultsThe histological sections have shown denser and enlarged marginal mitotic region of the developing eye lenses in FG and BFG. In vertical sections of the eye lenses the nuclei of the crystalline cells in FG and BFG show a highly depressed bow shaped arrangement. Moreover, the nuclei of the core crystalline cells of the lens were apparently smaller in FG and BFG than CG. Out of the six anatomical layers of the retina the nuclear and the plexiform layers were highly enlarged in FG and BFG, similarly the three corneal cell layers (endothelial, parenchymal and epithelial) were enlarged in FG and BFG than CG. The morphometric, histometric and micrometric estimations also show significant variations in FG and BFG than CG. ConclusionThe results indicate subtle developmental anomalies of the eyes attributable to the F-ions and BF exposure indicating their developmental neuro-optic disruption potentials. Results further revealed higher toxicity of BF as compared to F-ions.