Grandfathers-to-Grandsons Transgenerational Transmission of Exercise Positive Effects on Cognitive Performance.

Physical exercise is a robust lifestyle intervention known for its enhancement of cognitive abilities. Nevertheless, the extent to which these benefits can be transmitted across generations (intergenerational inheritance to F1, and transgenerational to F2 and beyond) remains a topic of limited comprehension. We have already shown that cognitive improvements resulting from physical exercise can be inherited from parents to their offspring, proving intergenerational effects. So, we set out to explore whether these enhancements might extend transgenerationally, impacting the F2 generation. In this study, we initially examined the behavioral traits of second generation (F2) male mice, whose grandfathers (F0) had an exercise intervention. Our findings revealed that F2 mice with physically active grandpaternal F0 progenitors displayed significantly improved memory recall, encompassing both spatial and non-spatial information when compared to their counterparts from sedentary F0 progenitors, and proving for the first time the transgenerational inheritance of physical exercise induced cognitive enhancement. Surprisingly, while F2 memory improved (as was the case with F1), adult hippocampal neurogenesis remained unchanged between experimental and control groups (unlike in F1). Additionally, our analysis of small RNA sequences in the hippocampus identified 35 differentially expressed miRNAs linked to important brain function categories. Notably, two of these miRNAs, miRNA-144 and miRNA-298, displayed a robust negative correlation with cognitive performance. These findings highlight the enduring transgenerational transmission of cognitive benefits associated with exercise, even after two generations, suggesting that moderate exercise training can have lasting positive effects, possibly orchestrated by a specific set of miRNAs that exert their influence across multiple generations.

Insights into adaptive behavioural plasticity from the guppy model system.

Behavioural plasticity allows organisms to respond to environmental challenges on short time scales. But what are the ecological and evolutionary processes that underlie behavioural plasticity? The answer to this question is complex and requires experimental dissection of the physiological, neural and molecular mechanisms contributing to behavioural plasticity as well as an understanding of the ecological and evolutionary contexts under which behavioural plasticity is adaptive. Here, we discuss key insights that research with Trinidadian guppies has provided on the underpinnings of adaptive behavioural plasticity. First, we present evidence that guppies exhibit contextual, developmental and transgenerational behavioural plasticity. Next, we review work on behavioural plasticity in guppies spanning three ecological contexts (predation, parasitism and turbidity) and three underlying mechanisms (endocrinological, neurobiological and genetic). Finally, we provide three outstanding questions that could leverage guppies further as a study system and give suggestions for how this research could be done. Research on behavioural plasticity in guppies has provided, and will continue to provide, a valuable opportunity to improve understanding of the ecological and evolutionary causes and consequences of behavioural plasticity.

Sex-specific transgenerational effects of diet on offspring life history and physiology.

Dietary variation in males and females can shape the expression of offspring life histories and physiology. However, the relative contributions of maternal and paternal dietary variation to phenotypic expression of latter generations is currently unknown. We provided male and female Drosophila melanogaster grandparents with diets differing in sucrose concentration prior to reproduction, and similarly subjected their grandoffspring to the same treatments. We then investigated the phenotypic consequences of this dietary variation among the grandsons and granddaughters. We observed transgenerational effects of dietary sucrose, mediated through the grandmaternal lineage, which mimic the direct effects of sucrose on lifespan, with opposing patterns across sexes; low sucrose increased female, but decreased male, lifespan. Dietary mismatching of grandoffspring-grandparent diets increased lifespan and reproductive success, and moderated triglyceride levels of grandoffspring, providing insights into the physiological underpinnings of the complex transgenerational effects on life histories.

Photoaged Nanopolystyrene Affects Neurotransmission to Induce Transgenerational Neurotoxicity in Caenorhabditis elegans.

Nanopolystyrene (NPS), a frequently employed nanoplastic, is an emerging environmental contaminant known to cause neurotoxicity in various organisms. However, the potential for transgenerational neurotoxic effects, especially from photoaged NPS (P-NPS), remains underexplored. This study investigated the aging of virgin NPS (V-NPS) under a xenon lamp to simulate natural sunlight exposure, which altered the physicochemical characteristics of the NPS. The parental generation (P0) of Caenorhabditis elegans was exposed to environmental concentrations (0.1-100 µg/L) of V-NPS and P-NPS, with subsequent offspring (F1-F4 generations) cultured under NPS-free conditions. Exposure to 100 µg/L P-NPS resulted in more pronounced deterioration in locomotion behavior in the P0 generation compared to V-NPS; this deterioration persisted into the F1-F2 generations but returned to normal in the F3-F4 generations. Additionally, maternal exposure to P-NPS damaged dopaminergic, glutamatergic, and serotonergic neurons in subsequent generations. Correspondingly, there was a significant decrease in the levels of dopamine, glutamate, and serotonin, associated with reduced expression of neurotransmission-related genes dat-1, eat-4, and tph-1 in the P0 and F1-F2 generations. Further analysis showed that the effects of P-NPS on locomotion behavior were absent in subsequent generations of eat-4(ad572), tph-1(mg280), and dat-1(ok157) mutants, highlighting the pivotal roles of these genes in mediating P-NPS-induced transgenerational neurotoxicity. These findings emphasize the crucial role of neurotransmission in the transgenerational effects of P-NPS on locomotion behavior, providing new insights into the environmental risks associated with exposure to photoaged nanoplastics.

Transgenerational Epigenetic Inheritance of Cardiovascular Diseases: A Network Medicine Perspective.

INTRODUCTION: The ability to identify early epigenetic signatures underlying the inheritance of cardiovascular risk, including trans- and intergenerational effects, may help to stratify people before cardiac symptoms occur. METHODS: Prospective and retrospective cohorts and case-control studies focusing on DNA methylation and maternal/paternal effects were searched in Pubmed from 1997 to 2023 by using the following keywords: DNA methylation, genomic imprinting, and network analysis in combination with transgenerational/intergenerational effects. RESULTS: Maternal and paternal exposures to traditional cardiovascular risk factors during critical temporal windows, including the preconceptional period or early pregnancy, may perturb the plasticity of the epigenome (mainly DNA methylation) of the developing fetus especially at imprinted loci, such as the insulin-like growth factor type 2 (IGF2) gene. Thus, the epigenome is akin to a "molecular archive" able to memorize parental environmental insults and predispose an individual to cardiovascular diseases onset in later life. Direct evidence for human transgenerational epigenetic inheritance (at least three generations) of cardiovascular risk is lacking but it is supported by epidemiological studies. Several blood-based association studies showed potential intergenerational epigenetic effects (single-generation studies) which may mediate the transmittance of cardiovascular risk from parents to offspring. DISCUSSION: In this narrative review, we discuss some relevant examples of trans- and intergenerational epigenetic associations with cardiovascular risk. In our perspective, we propose three network-oriented approaches which may help to clarify the unsolved issues regarding transgenerational epigenetic inheritance of cardiovascular risk and provide potential early biomarkers for primary prevention.

Lead exposure induced transgenerational developmental neurotoxicity by altering genome methylation in Drosophila melanogaster.

Heavy metal toxicity is a significant global health concern, with particular attention given to lead (Pb) exposure due to its adverse effects on cognitive development, especially in children exposed to low concentrations. While Pb neurotoxicity has been extensively studied, the analysis and molecular mechanisms underlying the transgenerational effects of Pb exposure-induced neurotoxicity remain poorly understood. In this study, we utilized Drosophila, a powerful developmental animal model, to investigate this phenomenon. Our findings demonstrated that Pb exposure during the developmental stage had a profound effect on the neurodevelopment of F0 fruit flies. Specifically, we observed a loss of correlation between the terminal motor area and muscle fiber area, along with an increased frequency of the ß-lobe midline crossing phenotype in mushroom bodies. Western blot analysis indicated altered expression levels of synaptic vesicle proteins, with a decrease in Synapsin (SYN) and an increase in Bruchpilot (BRP) expression, suggesting changes in synaptic vesicle release sites. These findings were corroborated by electrophysiological data, showing an increase in the amplitude of evoked excitatory junctional potential (EJP) and an increase in the frequency of spontaneous excitatory junctional potential (mEJP) following Pb exposure. Importantly, our results further confirmed that the developmental neurotoxicity resulting from grandparental Pb exposure exhibited a transgenerational effect. The F3 offspring displayed neurodevelopmental defects, synaptic function abnormalities, and repetitive behavior despite lacking direct Pb exposure. Our MeDIP-seq analysis further revealed significant alterations in DNA methylation levels in several neurodevelopmental associated genes (eagle, happyhour, neuroglian, bazooka, and spinophilin) in the F3 offspring exposed to Pb. These findings suggest that DNA methylation modifications may underlie the inheritance of acquired phenotypic traits resulting from environmental Pb exposure.

Epigenetic transgenerational effects of PM2.5 collected from southern Taiwan on sperm functions and DNA methylation in mouse offspring.

During respiration, particulate matter with a diameter of 2.5 µm or less (PM2.5) suspended in the atmosphere enters the terminal alveoli and blood. PM2.5 particles can attach to toxic substances, resulting in health problems. Limited information is available regarding the effects of prenatal exposure to water-soluble PM2.5 (WS-PM2.5) and water-insoluble PM2.5 (WI-PM2.5) on male reproduction. In addition, whether exposure to these particles has transgenerational effects remains unknown. We investigated whether prenatal exposure to WS-PM2.5 and WI-PM2.5 disrupts sperm function in generations F1, F2, and F3 of male mice. Pregnant BALB/c mice were treated using intratracheal instillation on gestation days 7, 11, and 15 with 10 mg of a water extract or insoluble PM2.5. On postnatal day 105, epididymal sperm count, motility, morphology, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, the sperm chromatin DNA fragmentation index (DFI), and testicular DNA methyltransferase (Dnmt) levels were evaluated in all generations. Whole-genome bisulfite sequencing was used to analyze the DNA methylation status of generation F3. According to the results, exposure to WS-PM2.5 affected sperm morphology, ROS production, and mean DFI in generation F1; ROS production and mean DFI in generation F2; and sperm morphology and MMP in generation F3. Similarly, exposure to WI-PM2.5 affected sperm morphology, ROS production, mean DFI, %DFI, and Dnmt1 expression in generation F1; sperm morphology, MMP, and ROS production in generation F2; and sperm morphology, ROS, and %DFI in generation F3. Two hypermethylated genes, PRR16 and TJP2, were observed in the WS-PM2.5 and WI-PM2.5 groups, two hypomethylated genes, NFATC1 and APOA5, were observed in the WS-PM2.5 group, and two hypomethylated genes, ZFP945 and GSE1, were observed in the WI-PM2.5 group. Hence, prenatal exposure to PM2.5 resulted in transgenerational epigenetic effects, which may explain certain phenotypic changes in male reproduction.

Multifaceted paternal exposures before conception and their epigenetic impact on offspring.

As scientific research progresses, there is an increasing understanding of the importance of paternal epigenetics in influencing the health and developmental path of offspring. Prior to conception, the environmental exposures and lifestyle choices of fathers can significantly influence the epigenetic state of sperm, including DNA methylation and histone changes, among other factors. These alterations in epigenetic patterns have the potential for transgenerational transmission potential and may exert profound effects on the biological characteristics of descendants. Paternal epigenetic changes not only affect the regulation of gene expression patterns in offspring but also increase the risk to certain diseases. It is crucial to comprehend the conditions that fathers are exposed to before conception and the potential outcomes of these conditions. This understanding is essential for assessing personal reproductive decisions and anticipating health risks for future generations. This review article systematically summarizes and analyzes current research findings regarding how paternal pre-pregnancy exposures influence offspring as well as elucidates underlying mechanisms, aiming to provide a comprehensive perspective for an enhanced understanding of the impact that paternal factors have on offspring health.

Cadmium Exposure in Male Rats Results in Ovarian Granulosa Cell Apoptosis in Female Offspring and Paternal Genetic Effects.

The aim of this study was to investigate whether the damage to male offspring induced by cadmium (Cd) exposure during embryonic period leads to the apoptosis of ovarian granulosa cells (OGCs) in the next generation of female offspring, and whether this apoptosis in the offspring was due to paternal genetic effects. Pregnant Sprague-Dawley (SD) rats were exposed to CdCl2 (0, 0.5, 2.0, or 8.0 mg/kg) by gavage daily for 20 days to produce the filial 1 (F1) generation. F1 males were mated with newly purchased females to produce the F2 generation, and the F3 generation was generated in the same way. No apoptotic bodies were observed in the OGCs of either the F2 or F3 generation as shown by electron microscopy, and a reduced OGC apoptosis rate (detected by flow cytometry) was observed in F2 OGCs from the Cd-exposed group. Moreover, the mRNA (qRT-PCR) levels of Bax and Bcl-2 and the protein (western blotting) level of pro-caspase-8 increased in the F2 generation (p < 0.05). The expression of apoptosis-related miRNAs (qRT-PCR) and methylation of apoptosis-related genes (determined via bisulfite-sequencing PCR) in OGCs were further determined. Compared with those of the controls, the expression patterns of microRNAs (miRNAs) in the F2 offspring were different in the Cd-exposed group. The miR-92a-2-5p expression levels were decreased in both the F2 and F3 generations (p < 0.05), while the average methylation level of apoptosis-related genes did not change significantly (except for individual loci). In summary, this study showed that the paternal genetic intergenerational effect of male Cd exposure during embryonic period induced apoptosis of OGCs in the offspring was weakened, and the transgenerational effect disappeared; nevertheless, intergenerational and transgenerational changes in apoptosis-related genes, epigenetic modifications, DNA methylation, and miRNAs were observed, and may be important for understanding the homeostatic mechanisms of the body to alleviate the intergenerational transmission of Cd-induced damage.

In silico investigation of the role of miRNAs in a possible developmental origin of prostate cancer in F1 and F2 offspring of mothers exposed to a phthalate mixture.

A previous study using miRNA sequencing revealed that exposure to a mixture of phthalates during pregnancy and lactation dysregulated rno-miR-184 and rno-miR-141-3p in the ventral prostate (VP) of offspring. Here, rno-miR-184 and rno-miR-141-3 expressions were obtained by RT-qPCR in the VP of F1 males as well as in F2 offspring, aiming to establish a relationship with possible oncogenic targets through in silico analyses with multigenerational approach. Additionally, some targets were measured by western blots to highlight a possible relationship between the deregulated miRNAs and some of their targets. VP samples from rats exposed to a mixture of phthalates maternally during pregnancy and lactation (GD10 to PND21-F1) and VP from offspring (F2) were examined. The phthalate mixture at both concentrations (20 µg and 200 mg/kg/day) increased the expression of both miRNAs in the F1 (PND22 and 120) and F2 (descendants of F1-treated males) prostate. Target prediction analysis revealed that both microRNAs are responsible for modulating the expression and synthesis of 40 common targets. A phthalate target association analysis and the HPA database showed an interesting relationship among these possible miRNAs modulated targets with prostate adenocarcinoma and other oncogenic processes. Western blots showed alteration in P63, P53, WNT5, and STAT3 expression, which are targeted by the miRNAs, in the VP of F1/F2 males. The data draw attention to the epigenetic modulation in the prostate of descendants exposed to phthalates and adds to one of the few currently found in the literature to point to microRNAs signature as biomarkers of exposure to plasticizers.

Effects of the temperature during embryonic development on adult reproduction and the phenotype of the second generation in zebra finches.

Across taxa, the temperature experienced by individuals early in life can have large effects on their development. However, comparatively little is known about whether the effects of this thermal developmental environment can be long-lasting or transgenerational. In birds, one important aspect of the developmental environment is incubation and, in general, eggs incubated at low temperatures produce offspring with smaller morphology, suboptimal physiology, and even lower long-term survival. Yet, little is known about whether incubation temperature may affect avian reproduction in adulthood, and nothing is known about whether the effects of avian incubation temperature may be transgenerational. To investigate this, we incubated zebra finch (Taeniopygia guttata) eggs at two different temperatures: 37.5 °C ('control') and 36.3 °C ('low'), raised nestlings until adulthood, and allowed same-temperature treatment pairs to reproduce. We found that F1 individuals incubated at the low temperature had shorter beaks at the start of reproduction than those incubated at the control temperature. Further, compared to those from control parents, F2 offspring from parents incubated at the low temperature had lighter body masses at 5 days-old and had shorter beaks at 30 days-old. However, we found little evidence that incubation temperature affected other aspects of reproduction, with no effect on latency to lay, clutch size, egg mass, incubation period, hatching success/asynchrony, fledging, or the number of offspring that ultimately survived until independence. Overall, we found some evidence that a difference in the early thermal developmental environment can have lasting morphological effects into the next generation. However, future work is needed to determine whether the incubation temperature that birds experience as embryos may influence parental care behaviors or lifetime reproductive success.

Interacting effects of environmental enrichment across multiple generations on early life phenotypes in zebrafish.

The environment plays an important role in an individual's development during early life, however, parents may also influence offspring development through so called "parental effects." We examined the effects of environmental enrichment in zebrafish (Danio rerio) across two generations through the paternal lineage. Fathers and grandfathers were exposed to either standard or high levels of housing enrichment for 4-weeks during adulthood. First-generation (F1) and second-generation (F2) offspring were obtained from controlled breeding and tested as larvae for changes in morphology at hatching stage (72hpf), and in locomotor activity at larval stage (120hpf) in both generations. We found paternal experience of enrichment resulted in changes in trunk length of F1 offspring and changes in spine curvature and dorsal length of F2 offspring, while changes in snout morphology of F2 offspring seemed to be driven by whether grandpaternal and paternal experience of the environment was matched or not. We found that while paternal enrichment increased the frequency of spontaneous movement in F1 and F2 offspring, interacting effects of paternal and grandpaternal enrichment on movement distance were seen in F2 offspring, and that spontaneous movement and the distance that larvae swam are thus distinct phenotypes that were differentially affected by the experiences of previous paternal generations. Taken together, these findings suggest that the parental and grandparental environment influence zebrafish behavior and morphology. The nature of these effects and the design of this study mean that these phenotypes were likely the result of nongenetic transmission through the paternal germline.

Parental environmental effects are common and strong, but unpredictable, in Arabidopsis thaliana.

The phenotypes of plants can be influenced by the environmental conditions experienced by their parents. However, there is still much uncertainty about how common and how predictable such parental environmental effects really are. We carried out a comprehensive experimental test for parental effects, subjecting plants of multiple Arabidopsis thaliana genotypes to 24 different biotic or abiotic stresses, or combinations thereof, and comparing their offspring phenotypes in a common environment. The majority of environmental stresses caused significant parental effects, with -35% to +38% changes in offspring fitness. The expression of parental effects was strongly genotype-dependent, and multiple environmental stresses often acted nonadditively when combined. The direction and magnitude of parental effects were unrelated to the direct effects on the parents: Some environmental stresses did not affect the parents but caused substantial effects on offspring, while for others, the situation was reversed. Our study demonstrates that parental environmental effects are common and often strong in A. thaliana, but they are genotype-dependent, act nonadditively, and are difficult to predict. We should thus be cautious with generalizing from simple studies with single plant genotypes and/or only few individual environmental stresses. A thorough and general understanding of parental effects requires large multifactorial experiments.

Photoaged Polystyrene Nanoplastics Result in Transgenerational Reproductive Toxicity Associated with the Methylation of Histone H3K4 and H3K9 in Caenorhabditis elegans.

Polystyrene nanoplastics (PS-NPs) are emerging environmental contaminants that are ubiquitously detected in various environments and have toxic effects on various organisms. Nevertheless, the transgenerational reproductive toxicity and underlying mechanisms of PS-NPs remain largely unknown, especially for photoaged PS-NPs under ultraviolet irradiation. In this study, only the parental generation (P0) was exposed to virgin and aged PS-NPs at environmentally relevant concentrations (0.1-100 µg/L), and subsequent generations (F1-F4) were cultured under normal conditions. Ultraviolet irradiation induced the generation of environmentally persistent free radicals and reactive oxygen species, which altered the physical and chemical characteristics of PS-NPs. The results of toxicity testing suggested that exposure to aged PS-NPs caused a more severe decrease in brood size, egg ejection rate, number of fertilized eggs, and hatchability than did the virgin PS-NPs in the P0, F1, and F2 generations. Additionally, a single maternal exposure to aged PS-NPs resulted in transgenerational effects on fertility in the F1 and F2 generations. Increased levels of H3K4 and H3K9 methylation were observed in the F1 and F2 generations, which were concomitant with the transgenerational downregulation of the expression of associated genes, such as spr-5, set-17, and met-2. On the basis of correlation analyses, the levels of histone methylation and the expression of these genes were significantly correlated to transgenerational reproductive effects. Further research showed that transgenerational effects on fertility were not observed in spr-5(by134), met-2(n4256), and set-17(n5017) mutants. Overall, maternal exposure to aged PS-NPs induced transgenerational reproductive effects via H3K4 and H3K9 methylation, and the spr-5, met-2, and set-17 genes were involved in the regulation of transgenerational toxicity. This study provides new insights into the potential risks of photoaging PS-NPs in the environment.

Wildfire and cattle legacies on gradients of soil nitrogen underlie patterns of annual brome invasion.

Human activities are increasing wildfires and livestock activity in arid ecosystems with potential implications for the spread of invasive grasses. The objective of this study was to test whether fire history and cattle activity alter soil resource gradients, thereby affecting patterns of Bromus rubens L. (red brome) invasion. Six paired burned and unburned transect lines (1-km long) were established in the northeast Mojave Desert along the boundaries of four independent wildfire scars. At 100-m transect increment points, we measured the distance to the two nearest cowpats, and two random points and measured the density, height, biomass, and seed production of red brome, soil moisture and inorganic nitrogen (N). Cattle activity was 29% greater along burned transects compared to unburned transects (P < 0.05). Red brome height, density, and seed production were 11-34% greater along burned transects than unburned transects (P < 0.05). Red brome height, biomass, density, and seed production were twofold to tenfold greater next to cowpats compared to random points (P < 0.05). Soils along burned transects and beneath cowpats had greater soil inorganic N (P < 0.05), which was positively correlated with red brome density, height, biomass, and seed production (R2 = 0.60-0.85, P < 0.0001). Transgenerational effects were evident as seeds from red brome next to cowpats had 27% higher germination than seeds collected from random points. Positive responses of red brome to increased inorganic N related to fire and cattle activity may contribute fine fuel infill that drives invasive grass-fire cycles in deserts.

Multi-generation reproductive toxicity of RDX and the involved signal pathways in Caenorhabditis elegans.

As one of the most frequently used explosives, hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) can cause persistent pollution in the environment, leading to the potential ecological threat crossing the generations. In this study, we employed Caenorhabditis elegans to explore the toxic effects of RDX on the parental and offspring worms and the involved signaling pathways. Exposure up to 1000 ng/mL of RDX produced a significant increase in reactive oxygen species (ROS) production, germ cell apoptosis, and decrease in eggs laid. Various mutants were used to demonstrate the RDX-induced apoptosis signaling pathway, and the metabolism of RDX in the nematodes was found related to cytochrome P450 and GST through RNA sequencing. Exposure of parental worms to RDX produced significant reproductive toxicity in F1 and F2, but was recovered in F3 and F4. The transgenerational effects were associated with the decreased expression of met-2, spr-5, and set-2. Our findings revealed the signaling pathways related to the reproductive toxicity caused by RDX in C. elegans and their future generations, which provided the basis for further exploration of the ecological risks of energetic compounds in the environment.

Exposure to lambda-cyhalothrin and abamectin drives sublethal and transgenerational effects on the development and reproduction of Cydia pomonella.

The codling moth Cydia pomonella (Lepidoptera: Tortricidae) is a major invasive pest of pome fruits and walnuts worldwide. Lambda-cyhalothrin (LCT) and abamectin (AM) have been frequently used in C. pomonella control, but control of this pest is very difficult because shortly after hatching, larvae of this insect bore tunnels and hide inside host plant fruit. In this study, a simulated field spray bioassay method was developed against neonate larvae of C. pomonella and concentration-response bioassays were conducted to evaluate the susceptibility of the neonate larvae to LCT and AM. Exposure of neonate larvae to sublethal concentration (LC30) of LCT or AM significantly reduced the survival rate of larvae (4th and 5th instars), lowered the mean weight of larvae and pupae, and decreased the daily maximal number of eggs laid and the total number of eggs laid (fecundity) per female. The sublethal effects, including reduced body mass, mean fecundity and net reproductive rate, extended mean generation time, and shortened oviposition period, were also found in transgenerational offspring. Furthermore, the transgenerational maternal effects were more obvious for AM than LCT, in comparison to the control. Additionally, the estimated population size was decreased by exposure to LC30 of LCT and AM, and the observed reduction of fecundity and population size within and across generations was likely the result of the downregulation of the reproduction-related vitellogenin gene (CpVg) after exposure to LC30 of LCT and AM. These results provide a better understanding of the overall effects of LCT and AM on C. pomonella and the transgenerational effects which should be taken into consideration when using insecticides in order to control C. pomonella.

Multigenerational genetic effects of paternal cadmium exposure on ovarian granulosa cell apoptosis.

To explore whether paternal cadmium (Cd) exposure causes ovarian granulosa cell (GC) apoptosis in offspring and the multigenerational genetic effects. From postnatal day 28 (PND28) until adulthood (PND56), SPF male Sprague-Dawley (SD) rats were gavaged daily with varying concentrations of CdCl2. (0, 0.5, 2, and 8 mg/kg). After treatment, the F1 generation was produced by mating with untreated female rats, and the F1 generation male rats were mated with untreated female rats to produce the F2 generation. Apoptotic bodies (electron microscopy) and significantly higher apoptotic rates (flow cytometry) were observed in both F1 and F2 ovarian GCs following paternal Cd exposure. Moreover, the mRNA (qRTPCR) or protein (Western blotting) levels of bax, bcl2, bcl-xl, caspase 3, caspase 8, and caspase 9 were changed to varying degrees. Apoptosis-related miRNAs (qRTPCR) and methylation modifications of apoptosis-related genes (bisulfite-sequencing PCR) in ovarian GCs were further detected. Compared with those of controls, the expression patterns of miRNAs in F1 and F2 offspring were different after paternal Cd exposure, while the average methylation level of apoptosis-related genes did not change significantly (except for individual loci). In summary, there are paternal genetic intergenerational and transgenerational effects on ovarian GC apoptosis induced by paternal Cd exposure. These genetic effects were related to the upregulation of BAX, BCL-XL, Cle-CASPASE 3, and Cle-CASPASE 9 in F1 and the upregulation of Cle-CASPASE 3 in F2 progeny. Important changes in apoptosis-related miRNAs were also observed.

Impact of sublethal concentrations of flonicamid on key demographic parameters and feeding behavior of Schizaphis graminum.

Flonicamid is a novel systemic insecticide that efficiently controls sap-sucking insect pests. However, the impact of sublethal concentrations of flonicamid on key demographic parameters and the feeding behavior of greenbug, Schizaphis graminum has not yet been studied. In this study, we used the age stage, two-sex life table approach, and electrical penetration graphs (EPGs) to investigate the sublethal effects of flonicamid on the biological traits and feeding behavior of S. graminum. Bioassays showed that flonicamid possesses high toxicity to adult S. graminum with LC50 of 5.111 mg L-1 following 48 h exposure. Sublethal concentrations of flonicamid (LC5 and LC10) significantly decreased the longevity and fecundity of directly exposed parental aphids (F0), while the reproductive days were reduced only at LC10. The pre-adult stage and total pre-reproductive period (TPRP) increased in F1 individuals after exposure of F0 aphids to the sublethal concentrations of flonicamid. Furthermore, the adult longevity, fecundity and key demographic parameters (R0, r, and λ) were significantly reduced in progeny generation (F1). EPG recordings showed that the total duration of phloem sap ingestion and concurrent salivation (E2) decreased substantially in F0 and F1 aphids after exposure to LC5 and LC10 of flonicamid. Taken together, our results showed that the sublethal concentrations of flonicamid affect the demographic parameters and feeding behavior that ultimately suppress the population growth of S. graminum. This study provides in-depth information about the overall effects of flonicamid on S. graminum that might help to manage this key pest.

Sublethal and transgenerational effects of lufenuron on biological characteristics and expression of reproductive related genes in the fall armyworm, Spodoptera frugiperda.

The fall armyworm, Spodoptera frugiperda, is a notorious polyphagous pest that causes serious economic losses in crucial crops and has invaded Africa and Asia. Lufenuron is widely used for controlling S. frugiperda in China, owing to its high toxicity against this key pest, and less pollution and little impact on natural enemies. In the present study, the sublethal and transgenerational effects of lufenuron on S. frugiperda were investigated to provide in-depth information for the rational use of lufenuron. Results showed that the development time and pupae weight were not significantly affected following exposure of females to LC10 and LC25 and male S. frugiperda to the LC10 of lufenuron. However, LC25 exposure significantly reduced pupal and total development time and pupae weight of male S. frugiperda. The longevity of S. frugiperda adults was prolonged by lufenuron and the fecundity of S. frugiperda treated with LC10 of lufenuron was significantly increased by 40% compared to the control. In addition, our study demonstrated that the LC25 of lufenuron had transgenerational effects on the progeny generation. The development time of female S. frugiperda whose parents were exposed to LC25 of lufenuron was significantly decreased compared to the control. And then, the expression profiles of Vg, VgR, JHEH, JHE, JHAMT, JHBP, CYP307A1, CYP306A1, CYP302A1 and CYP314A1 genes involved in insect reproduction and development were analyzed using Quantitative Real-Time PCR (RT-qPCR). Results showed that Vg, VgR, JHE, JHAMT, and CYP306A1 were significantly upregulated at the LC10 of lufenuron, which revealed that these upregulated genes might be linked with increased fecundity of S. frugiperda. Taken together, these findings highlighted the importance of sublethal and transgenerational effects under laboratory conditions and these effects may change the population dynamics in the field. Therefore, our study provided valuable information for promoting the rational use of lufenuron for controlling S. frugiperda.