Thermal conditioning of quail embryos has transgenerational and reversible long‑term effects

Background In the current context of global warming,thermal manipulation of avian embryos has received increasing attention as a strategy to promote heat tolerance in avian species by simply increasing the egg incubation temperature.However,because of their likely epigenetic origin,thermal manipulation effects may last more than one generation with consequences for the poultry industry.In this work,a multigenerational and transgenerational analysis of thermal manipulation during embryogenesis was performed to uncover the long-term effects of such procedure.Results Thermal manipulation repeated during 4 generations had an effect on hatchability,body weight,and weight of eggs laid in Japanese quails,with some effects increasing in importance over generations.Moreover,the effects on body weight and egg weight could be transmitted transgenerationally,suggesting non-genetic inheritance mechanisms.This hypothesis is reinforced by the observed reversion of the effect on growth after five unexposed generations.Interestingly,a beneficial effect of thermal manipulation on heat tolerance was observed a few days after hatching,but this effect was not transgenerational.Conclusions Our multigenerational study showed that thermal conditioning of quail embryos has a beneficial effect on post-hatch heat tolerance hampered by transgenerational but reversible defects on growth.Assuming that no genetic variability underlies these changes,this study provides the first demonstration of epigenetic inheritance of traits induced by environmental temperature modification associated with long-term impacts in an avian species.

Clonal Transgenerational Effects Transmit for Multiple Generations in a Floating Plant

Environmental conditions of a parent plant can influence the performance of their clonal offspring,and such clonal transgenerational effects may help offspring adapt to different environments.However,it is still unclear how many vegetative generations clonal transgenerational effects can transmit for and whether it depends on the environmental conditions of the offspring.We grew the ancestor ramets of the floating clonal plant Spirodela polyrhiza under a high and a low nutrient level and obtained the so-called 1^(st)-generation offspring ramets of two types(from these two environments).Then we grew the 1^(st)-generation offspring ramets of each type under the high and the low nutrient level and obtained the so-called 2^(nd)-generation offspring ramets of four types.We repeated this procedure for another five times and analyzed clonal transgenerational effects on growth,morphology and biomass allocation of the 1^(st)-to the 6^(th)-generation offspring ramets.We found positive,negative or neutral(no)transgenerational effects of the ancestor nutrient condition on the offspring of S.polyrhiza,depending on the number of vegetative generations,the nutrient condition of the offspring environment and the traits considered.We observed significant clonal transgenerational effects on the 6^(th)-generation offspring;such effects occurred for all three types of traits(growth,morphology and allocation),but varied depending on the nutrient condition of the offspring environment and the traits considered.Our results suggest that clonal transgenerational effects can transmit for multiple vegetative generations and such impacts can vary depending on the environmental conditions of offspring.

Alternative models for transgenerational epigenetic inheritance:Molecular psychiatry beyond mice and man

Mental illness remains the greatest chronic health burden globally with few inroads having been made despite significant advances in genomic knowledge in recent decades.The field of psychiatry is constantly challenged to bring new approaches and tools to address and treat the needs of vulnerable individuals and subpopulations,and that has to be supported by a continuous growth in knowledge.The majority of neuropsychiatric symptoms reflect complex geneenvironment interactions,with epigenetics bridging the gap between genetic susceptibility and environmental stressors that trigger disease onset and drive the advancement of symptoms.It has more recently been demonstrated in preclinical models that epigenetics underpins the transgenerational inheritance of stressrelated behavioural phenotypes in both paternal and maternal lineages,providing further supporting evidence for heritability in humans.However,unbiased prospective studies of this nature are practically impossible to conduct in humans so preclinical models remain our best option for researching the molecular pathophysiologies underlying many neuropsychiatric conditions.While rodents will remain the dominant model system for preclinical studies(especially for addressing complex behavioural phenotypes),there is scope to expand current research of the molecular and epigenetic pathologies by using invertebrate models.Here,we will discuss the utility and advantages of two alternative model organisms–Caenorhabditis elegans and Drosophila melanogaster-and summarise the compelling insights of the epigenetic regulation of transgenerational inheritance that are potentially relevant to human psychiatry.

Small RNAs and Transgenerational Epigenetic Variation

Small RNAs are found in eukaryotes and are responsible for regulation of chromatin structure, RNA processing and stability, translation and transcription. 24-nt small interfering RNA (siRNA) are known to mediate gene inactivation via the RNA-directed DNA methylation pathway (RdDM) and are important for natural heritable changes in plant species. DNA cytosine methylation can be maintained between generations and this may be important for accelerated adaption to stress conditions. Research is currently focused toward the epigenetic response to disease, the stability of DNA methylation over generations, the elucidation of newly discovered pathways for de novo DNA methylation, and the application of epigenetic variation to breeding programs. This review aims to give a brief but comprehensive examination on small RNAs and transgenerational epigenetic variation.

Transgenerational Transmission of Addiction Problems

This paper aims to evaluate the possible transgenerational transmission of a mechanism of addiction triggered by a specific type of attachment and the prevalence of psychological trauma in the descendants. 22 adults (alcoholics, drug addicts, and heroin addicts) aged 23 to 56 followed in an addictology treatment centre are participated. Measurements: We evaluated the prevalence of family ascendants on our population using two semi structured interviews and a genogram. Potential psychological trauma was measured with the Child Trauma Questionnaire (CTQ) and the quality of attachment with the Attachment Style Questionnaire (ASQ). Findings: 95% of patients have direct ascendants who suffer from addiction. 86% of patients suffered emotional negligence during childhood. Physical abuse is frequent (41%) as well as emotional abuse (50%), which proves a form of mistreatment and explains the presence of an insecure attachment. Conclusion: Addicts have often been neglected and have lived in emotional deprivation during childhood, which is the reason for an insecure attachment. The ascendants, who often suffer from addiction themselves, have, because of their pathology, contributed to a possible transgenerational transmission of the mechanism of addiction via the quality of the affective links with their children.

Parental and transgenerational impairments of thyroid endocrine system in zebrafish by 2,4,6-tribromophenol

Many environmental contaminants could be transmitted fromparents and generate impairments to their progeny.The 2,4,6-tribromophenol(TBP),a novel brominated flame retardant which has been frequently detected in various organisms,was supposed to be bioaccumulated and intergenerational transmitted in human beings.Previous studies revealed that TBP could disrupt thyroid endocrine system in zebrafish larvae.However,there is no available data regarding the parental and transgenerational toxicity of this contaminant.Thus,in this study adult zebrafish were exposed to environmental contaminated levels of TBP for 60 days to investigate the parental and transgenerational impairments on thyroid endocrine system.Chemical analysis verified the bioaccumulation of TBP in tested organs of parents(concentration:liver>gonads>brain)and its transmission into eggs.For adults,increased thyroid hormones,disturbed transcriptions of related genes and histopathological changes in thyroid follicles indicate obvious thyroid endocrine disruptions.Transgenerational effects are indicated by the increased thyroid hormones both in eggs(maternal source)and in developed larvae(newly synthesized),aswell as disrupted transcriptional profiles of key genes in HPT axis.The overall results suggest that the accumulated TBP could be transmitted from parent to offspring and generate thyroid endocrine disruptions in both generations.

Gestational dexamethasone exposure impacts hippocampal excitatory synaptic transmission and learning and memory function with transgenerational effects

The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons.Here we explored how gestational exposure to dexamethasone,a synthetic glucocorticoid commonly used in clinical practice,has lasting effects on offspring's learning and memory.Adult offspring rats of prenatal dexamethasone exposure(PDE)displayed significant impairments in novelty recognition and spatial learning memory,with some phenotypes maintained transgenerationally.PDE impaired synaptic transmission of hippocampal excitatory neurons in offspring of F1 to F3 generations,and abnormalities of neurotransmitters and receptors would impair synaptic plasticity and lead to impaired learning and memory,but these changes failed to carry over to offspring of F5 and F7 generations.Mechanistically,altered hippocampal miR-133a-3p-SIRT1-CDK5-NR2B signaling axis in PDE multigeneration caused inhibition of excitatory synaptic transmission,which might be related to oocyte-specific high expression and transmission of miR-133a-3p.Together,PDE affects hippocampal excitatory synaptic transmission,with lasting consequences across generations,and CDK5 in offspring's peripheral blood might be used as an early-warning marker for fetal-originated learning and memory impairment.

Synthetic apomixis enables stable transgenerational transmission of heterotic phenotypes in hybrid rice

In hybrid plants,heterosis often produces large,vigorous plants with high yields;however,hybrid seeds are generated by costly and laborious crosses of inbred parents.Apomixis,in which a plant produces a clone of itself via asexual reproduction through seeds,may produce another revolution in plant biology.Recently,synthetic apomixis enabled clonal reproduction of F_(1) hybrids through seeds in rice(Oryza sativa),but the inheritance of the synthetic apomixis trait and superior heterotic phenotypes across generations remained unclear.Here,we propagated clonal plants to the T_(4) generation and investigated their genetic and molecular stability at each generation.By analyzing agronomic traits,as well as the genome,methylome,transcriptome,and allele-specific transcriptome,we showed that the descendant clonal plants remained stable.Unexpectedly,in addition to normal clonal seeds,the plants also produced a few aneuploids that had eliminated large genomic segments in each generation.Despite the identification of rare aneuploids,the observation that the synthetic apomixis trait is stably transmitted through multiple generations helps confirm the feasibility of using apomixis in the future.

Molecular insights into the transgenerational inheritance of stress memory

There is accumulating evidence to show that environmental stressors can regulate a variety of phenotypes in descendants through germline-mediated epigenetic inheritance. Studies of model organisms exposed to environmental cues(e.g., diet, heat stress, toxins) indicate that altered DNA methylations, histone modifications, or non-coding RNAs in the germ cells are responsible for the transgenerational effects. In addition,it has also become evident that maternal provision could provide a mechanism for the transgenerational inheritance of stress adaptations that result from ancestral environmental cues. However, how the signal of environmentally-induced stress response transmits from the soma to the germline, which may influence offspring fitness, remains largely elusive. Small RNAs could serve as signaling molecules that transmit between tissues and even across generations. Furthermore, a recent study revealed that neuronal mitochondrial perturbations induce a transgenerational induction of the mitochondrial unfolded protein response mediated by a Wnt-dependent increase in mitochondrial DNA levels. Here, we review recent work on the molecular mechanism by which parental experience can affect future generations and the importance of soma-to-germline signaling for transgenerational inheritance.

Transgenerational phenotypic plasticity of diapause induction and related fitness cost in a commercial strain of the parasitoid Aphidius ervi Haliday

Diapause is an adaptation that insects have evolved to synchronize their life cycle with that of seasonal climatic changes and resources availability.However,cues for its induction are not always clear and,in some cases,a maternal effect may be involved.At the population level,just a part of the individuals may exhibit diapause with important consequences in terms of winter survival.Moreover,clear indicators of diapause state are difficult to identify.Diapause induction was thus investigated in the aphid parasitoid species Aphidius ervi Haliday(Hymenoptera:Braconidae)developing in the aphid Sitobion avenae(Hemiptera:Aphididae)at four crossed photothermal regimes(16℃and 8℃,16:8 h L:D and 8:16 h L:D),and during 2 successive generations.We analyzed the reliability of changes in mummy color to assess for the diapausing state compared to dissections,and we measured parasitoid morphological and physiological traits.We observed that the proportion of dark brown mummies increased after one generation under low photothermal regime compared to other regimes.No diapause was recorded at 16℃,16:8 h L:D,while we observed 16.2%and 67.5%diapause incidence at 8℃,8:16 h L:D,at 1st and 2nd generation,respectively.Diapause induction is thus increased by short day-length conditions and low temperatures as well as by maternal effects.All parasitoid life-history traits(weight,size,fat content,water content,egg-load,and longevity)were affected by the photothermal regime and/or the generation.These results raise new questions on the environmental thresholds needed to induce diapause and on survival and adaptation potential of commercially available parasitoid strains in different environments.

Offspring diet supersedes the transgenerational effects of parental diet in a specialist herbivore Neolema abbreviata under manipulated foliar nitrogen variability

Diet quality influences organismal fitness within and across generations.For herbivorous insects,the transgenerational effecets of diet remain relatively underexplored.Usinga3×3×2 factorial experiment,we evaluated how N enrichment in parental diets of Neolemd abbreviata(Larcordaire)(C oleoptera:Chrysomelidae),a biological control agent for Tradescantia fluminensis Vell.(Commelinaceae),may influence life history and performance of Fi and F2 offspring under reciprocal experiments.We found limited transgenerational effects of foliar nitrogen variability among life-history traits in both larvae and adults.Larval weight gain and mortality were responsive to parental diet contrary to feeding damage,pupal weight and duration taken to pupate.There were significant parental diet x test interactions in larval feeding damage,weight gain,pupal weight and time to pupation.Generally,offspring from parents under high N plants performed better even under low N test plants.Adult traits including oviposition selection,feeding weight and longevity did not respond to the efects of parental diet nor its interaction with test diet as was the case in the larval stage.However,the main efects of test diet were more important in determining adult performance in both generations suggesting limited sensitivity to parental diet in the adult stage.Our results show conflicting responses to parental diet between larvae and adults ofthe same generation among an insec species with both actively feeding larual and adult life stagee These tranegeneratinonal efferte,or lack thereof,may have implications on the field performance of N.abbrevita under heterogencous nutritional landscapes.

Paternal transgenerational nutritional epigenetic effect:A new insight into nutritional manipulation to reduce the use of antibiotics in animal feeding

The use of antibiotics in animal feeding has been banned in many countries because of increasing concerns about the development of bacterial resistance to antibiotics and potential issues on food safety.Searching for antibiotic substitutes is essential.Applying transgenerational epigenetic technology to animal production could be an alternative.Some environmental changes can be transferred to memorylike responses in the offspring through epigenetic mechanisms without changing the DNA sequence.In this paper,we reviewed those nutrients and non-nutritional additives that have transgenerational epigenetic effects,including some amino acids,vitamins,and polysaccharides.The paternal transgenerational nutritional epigenetic regulation was particularly focused on mechanism of the substantial contribution of male stud animals to the animal industries.We illustrated the effects of paternal transgenerational epigenetics on the metabolism and immunity in farming animals and proposed strategies to modulate male breeding livestock or poultry.

Priming: A promising strategy for crop production in response to future climate

Anticipated more frequent extreme events due to changes in global climatic variability requires adaptation of crop species to multi-occurrence abiotic stresses hereby sustaining the food security. Priming, by pre-exposure of plants to an eliciting factor, enables plants to be more tolerant to later biotic or abiotic stress events. Priming induced "stress memory" exists in both present generation and the offspring. Thus, priming is suggested to be a promising strategy for plants to cope with the abiotic stresses under global change scenarios. In this review, the underlying physiological and molecular mechanisms of priming induced enhancement of stress tolerance to the major abiotic stresses of drought and waterlogging, and high and low temperature in crop plants were discussed, and the potential to utilize the priming effect for sustaining crop productivity in future climates was also suggested.

Perinatal nutritional programming of health and metabolic adult disease

Data indicate that perinatal nutritional insults not onlyhave short-term consequences on the growth velocity of the fetus/neonate but also sensitize to the development of metabolic adult diseases.The pathophysiological mechanisms involved in the so-called "Developmental Origin of Health and Adult Diseases" are still largely unknown and depend on the type of alteration (nutritional,psychological,endocrine disruptors,etc.),its intensity and duration,species,sex and the time during which it is applied.Perinatal stress,via disturbances of both hy-pothalamo-pituitary-adrenal (HPA) axis and sympathoadrenal-system (SAS),as well as brain-adipose axis and pancreas alterations could play a crucial role.Interestingly,it has been demonstrated that perinatal insults may be transmitted transgenerationally,suggesting that these long-term consequences may be inherited via epigenetic mechanisms.Finally,since the placenta has been demonstrated to be sensitive to perinatal nutritional manipulations,the identification of placental markers may thus represent an important new avenue to identify the more susceptible babies prone to developing meta-bolic diseases.

Research Progress of Maternal Environmental Effects in Resource-based Regions

Heavy metal pollution is common in resource-based regions.However,the morphological,physiological and biochemical mechanisms of plants transmitting environmental information to their offspring in environments polluted by heavy metals have not been studied yet.Taking soybean,an annual self-pollinated plant in Huang-Huai-Hai region,as the research object,the morphological,physiological and biochemical indexes and heavy metal enrichment and distribution characteristics of plants under heavy metal stress were monitored continuously for about three generations,and the trans-generational differences of soybean reproduction,vegetative growth,stress resistance and life cycle in heavy metal stress environment were elucidated.The results will be helpful to better understand the long-term adaptive strategy of plants to heavy metal stress and provide the theory basis for ecological security of soybean and other crops under heavy metal stress.

A Study of the Trans-Generational Trauma in Everything I Never Told You

Celeste Ng’s first novel Everything I Never Told is about a tragedy that happened in a mixed race family,the family of a Chinese American college professor and his stay-at-home white wife in a small Ohio town in the 1970s.The novel looks at the trau⁃matic events suffered by the Chinese American family,but facing the traumatic memory and reshaping the family relationship are the writing purposes of Celeste Ng.Based on trauma theory,the transmission of trauma in Chinese American families would be dis⁃cussed.This kind of trauma not only harms the parents'generation,but also affects the healthy growth of the children's generation.The aim of the novel is to find a way to recover from such traumatic transmission.

Systematic characterization of small RNAs associated with C.elegans Argonautes

Argonaute proteins generally play regulatory roles by forming complexes with the corresponding small RNAs(s RNAs).An expanded Argonaute family with 20 potentially functional members has been identified in Caenorhabditis elegans.Canonical s RNAs in C.elegans are mi RNAs,small interfering RNAs including 22G-RNAs and 26G-RNAs,and 21U-RNAs,which are C.elegans pi RNAs.Previous studies have only covered some of these Argonautes for their s RNA partners,and thus,a systematic study is needed to reveal the comprehensive regulatory networks formed by C.elegans Argonautes and their associated s RNAs.We obtained in situ knockin(KI)strains of all C.elegans Argonautes with fusion tags by CRISPR/Cas9 technology.RNA immunoprecipitation against these endogenously expressed Argonautes and high-throughput sequencing acquired the s RNA profiles of individual Argonautes.The s RNA partners for each Argonaute were then analyzed.We found that there were 10Argonautes enriched mi RNAs,17 Argonautes bound to 22G-RNAs,8 Argonautes bound to 26G-RNAs,and 1 Argonaute PRG-1bound to pi RNAs.Uridylated 22G-RNAs were bound by four Argonautes HRDE-1,WAGO-4,CSR-1,and PPW-2.We found that all four Argonautes played a role in transgenerational epigenetic inheritance.Regulatory roles of the corresponding Argonaute-s RNA complex in managing levels of long transcripts and interspecies regulation were also demonstrated.In this study,we portrayed the s RNAs bound to each functional Argonaute in C.elegans.Bioinformatics analyses together with experimental investigations provided perceptions in the overall view of the regulatory network formed by C.elegans Argonautes and s RNAs.The s RNA profiles bound to individual Argonautes reported here will be valuable resources for further studies.

Advances in research into gamete and embryo-fetal origins of adult diseases

The fetal and infant origins of adult disease hypothesis proposed that the roots of adult chronic disease lie in the effects of adverse environments in fetal life and early infancy. In addition to the fetal period, fertilization and early embryonic stages, the critical time windows of epigenetic reprogramming, rapid cell differentiation and organogenesis, are the most sensitive stages to environmental disturbances. Compared with embryo and fetal development, gametogenesis and maturation take decades and are more vulnerable to potential damage for a longer exposure period. Therefore, we should shift the focus of adult disease occurrence and pathogenesis further back to gametogenesis and embryonic development events, which may result in intergenerational, even transgenerational, epigenetic re-programming with transmission of adverse traits and characteristics to offspring. Here, we focus on the research progress relating to diseases that originated from events in the gametes and early embryos and the potential epigenetic mechanisms involved.

Normal epigenetic inheritance in mice conceived by in vitro fertilization and embryo transfer

An association between assisted reproductive technology (ART) and neurobehavioral imprinting disorders has been reported in many studies,and it seems that ART may interfere with imprint reprogramming.However,it has never been explored whether epigenetic errors or imprinting disease susceptibility induced by ART can be inherited transgenerationally.Hence,the aim of this study was to determine the effect of in vitro fertilization and embryo transfer (IVF-ET) on transgenerational inheritance in an inbred mouse model.Mice derived from IVF-ET were outcrossed to wild-type C57BL/6J to obtain their female and male line F2 and F3 generations.Their behavior,morphology,histology,and DNA methylation status at several important differentially methylated regions (DMRs) were analyzed by Morris water maze,hematoxylin and eosin (H&E) staining,and bisulfite genomic sequencing.No significant differences in spatial learning or phenotypic abnormality were found in adults derived from IVF (F1) and female and male line F2 and F3 generations.A borderline trend of hypomethylation was found in H19 DMR CpG island 3 in the female line-derived F3 generation (0.40±0.118,P=0.086).Methylation status in H19/Igf2 DMR island 1,Igf2 DMR,KvDMR,and Snrpn DMR displayed normal patterns.Methylation percentage did not differ significantly from that of adults conceived naturally,and the expression of the genes they regulated was not disturbed.Transgenerational integrity,such as behavior,morphology,histology,and DNA methylation status,was maintained in these generations,which indicates that exposure of female germ cells to hormonal stimulation and gamete manipulation might not affect the individuals and their descendents.

Fitness costs of reflex bleeding in the ladybird beetle Harmonia axyridis: the role of parental effects

Reflex bleeding is an important antipredator defense mechanism in Coccinellidae.We examined the costs of reflex bleeding in larval and adult stages of the ladybird beetle Harmonia axyridis on offspring fitness and reproductive performance through the comparisons between bled and control larvae,reciprocal crosses of bled/control beetles,and early and late clutch phenotypes.Beetles bled during their larval stage spent a longer time in development and weighed less than controls.Egg fertility was reduced for crosses where either one or both parents had been bled during the larval or adult stage.Offspring crosses that included a parent bled during the larval stage suffered fitness costs in development and female body mass,while those bled during the adult stage suffered no transgenerational costs.Males that suffered bleeding during their larval stage accelerated progeny development of nonbled females in early clutches,suggesting a positive transgenerational effect of larval bleeding,while males that did not suffer bleeding accelerated progeny development of bled females in later clutches.As the underlying effects of bleeding on females'offspring in the early clutches were diminished in the late ones,suggesting another transgenerational effect.The strengths of maternal and paternal effects on progeny development of parents bled at the larval stage were higher in earlier clutches.This study suggests that H.axyridis adults are less affected than larvae by the frequent use of the defensive secretions in their stressful habitats.