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Reproduction, mortality, and immune function often change with age but do not invariably deteriorate. Across the tree of life, there is extensive variation in age-specific performance and changes to key life-history traits. These changes occur on a spectrum from classic senescence, where performance declines with age, to juvenescence, where performance improves with age. Reproduction, mortality, and immune function are also important factors influencing the spread of infectious disease, yet there exists no comprehensive investigation into how the aging spectrum of these traits impacts epidemics. We used a model laboratory infection system to compile an aging profile of a single organism, including traits directly linked to pathogen susceptibility and those that should indirectly alter pathogen transmission by influencing demography. We then developed generalizable epidemiological models demonstrating that different patterns of aging produce dramatically different transmission landscapes: in many cases, aging can reduce the probability of epidemics, but it can also promote severity. This work provides context and tools for use across taxa by empiricists, demographers, and epidemiologists, advancing our ability to accurately predict factors contributing to epidemics or the potential repercussions of senescence manipulation.

Oxidative stress (OS) experienced early in life can affect an individual¿s phenotype. However, its consequences for the next generation remain largely unexplored.Wemanipulated the OS level endured by zebra finches (Taeniopygia guttata) during their development by transitorily inhibiting the synthesis of the key antioxidant glutathione ("early-high-OS"). The offspring of these birds and control parents were cross fostered at hatching to enlarge or reduce its brood size. Independent of parents¿ early-life OS levels, the chicks raised in enlarged broods showed lower erythrocyte glutathione levels, revealing glutathione sensitivity to environmental conditions. Control biological mothers produced females, not males, that attained a higher body mass when raised in a benign environment (i.e., the reduced brood). In contrast, biological mothers exposed to early-lifeOS produced heavier males, not females, when allocated in reduced broods. Early-life OS also affected the parental rearing capacity because 12-day-old nestlings raised by a foster pair with both early-high-OS members grew shorter legs (tarsus) than chicks from other groups. The results indicate that environmental conditions during development can affect early glutathione levels, which may in turn influence the next generation through both pre- and postnatal parental effects. The results also demonstrate that earlylife OS can constrain the offspring phenotype., Financial support was obtained from projects CGL2009-10883-C02-02, CGL2015-69338-C2-2-P,and PID2019-109303GB-I00 from Ministerio de Ciencia e Innovación (MICIN; Spain). A.A.R.-H. was funded by a Formación de Personal Investigador (FPI) grantfrom MICIN and by Marie Skłodowska-Curie grantagreement 842085 from the European Union’s Horizon2020 research and innovation program.

There is very little information on the transgenerational or genetic effects of low dose-rate ionizing radiation. We report the detection of the transgenerational effects of chronic low dose-rate irradiation in mice, at the molecular level in the whole genome, using array comparative genomic hybridization technology. We observed that the number of the mice with de novo copy number variations (specifically, deletions) was significantly increased in the offspring of C57BL/6J male mice exposed to 20 mGy/day gamma-rays for 400 days (total dose: 8000 mGy), as compared to non-irradiated controls. We did not detect any difference in the size of the de novo deletions between the irradiated and the non-irradiated groups. An analysis of the life span of the offspring suggested a possibility that de novo copy-number variations may be associated with shorter life spans.

Oocytes and preimplantation embryos require careful regulation of the redox environment for optimal development both in vivo and in vitro. Reactive oxygen species (ROS) are generated throughout development as a result of cellular metabolism and enzyme reactions. ROS production can result in (i) oxidative eustress, where ROS are helpful signalling molecules with beneficial physiological functions and where the redox state of the cell is maintained within homeostatic range by a closely coupled system of antioxidants and antioxidant enzymes, or (ii) oxidative distress, where excess ROS are deleterious and impair normal cellular function. in vitro culture of embryos exacerbates ROS production due to a range of issues including culture-medium composition and laboratory culture conditions. This increase in ROS can be detrimental not only to assisted reproductive success rates but can also result in epigenetic and genetic changes in the embryo, resulting in transgenerational effects. This review examines the effects of oxidative stress in the oocyte and preimplantation embryo in both the in vivo and in vitro environment, identifies mechanisms responsible for oxidative stress in the oocyte/embryo in culture and approaches to reduce these problems, and briefly examines the potential impacts on future generations.

Author(s): Chamorro-Garcia, Raquel; Poupin, Nathalie; Tremblay-Franco, Marie; Canlet, Cecile; Egusquiza, Riann; Gautier, Roselyne; Jouanin, Isabelle; Shoucri, Bassem M; Blumberg, Bruce; Zalko, Daniel | Abstract: BackgroundEndocrine disrupting chemicals (EDCs) contribute to the etiology of metabolic disorders such as obesity, insulin resistance and hepatic dysfunction. Concern is growing about the consequences of perinatal EDC exposure on disease predisposition later in life. Metabolomics are promising approaches for studying long-term consequences of early life EDC exposure. These approaches allow for the identification and characterization of biomarkers of direct or ancestral exposures that could be diagnostic for individual susceptibility to disease and help to understand mechanisms through which EDCs act.ObjectivesWe sought to identify metabolomic fingerprints in mice ancestrally exposed to the model obesogen tributyltin (TBT), to assess whether metabolomics could discriminate potential trans-generational susceptibility to obesity and recognize metabolic pathways modulated by ancestral TBT exposure.MethodsWe used non-targeted 1H NMR metabolomic analyses of plasma and liver samples collected from male and female mice ancestrally exposed to TBT in two independent transgenerational experiments in which F3 and F4 males became obese when challenged with increased dietary fat.ResultsMetabolomics confirmed transgenerational obesogenic effects of environmentally relevant doses of TBT in F3 and F4 males, in two independent studies. Although females never became obese, their specific metabolomic fingerprint evidenced distinct transgenerational effects of TBT in female mice consistent with impaired capacity for liver biotransformation.DiscussionThis study is the first application of metabolomics to unveil the transgenerational effects of EDC exposure. Very early, significant changes in the plasma metabolome were observed in animals ancestrally exposed to TBT. These changes preceded the onset of obesogenic effects elicited by increased dietary fat in the TBT groups, and which ultimately resulted in significant changes in the liver metabolome. Development of metabolomic fingerprints could facilitate the identification of individuals carrying the signature of ancestral obesogen exposure that might increase their susceptibility to other risk factor such as increased dietary fat.

Premise Plant maternal effects on offspring phenotypes are well documented. However, little is known about how herbivory on maternal plants affects offspring fitness. Furthermore, while inbreeding is known to reduce plant reproductive output, previous studies have not explored whether and how such effects may extend across generations. Here, we addressed the transgenerational consequences of herbivory and maternal plant inbreeding on the reproduction of Solanum carolinense offspring. Methods Manduca sexta caterpillars were used to inflict weekly damage on inbred and outbred S. carolinense maternal plants. Cross‐pollinations were performed by hand to produce seed from herbivore‐damaged outbred plants, herbivore‐damaged inbred plants, undamaged outbred plants, and undamaged inbred plants. The resulting seeds were grown in the greenhouse to assess emergence rate and flower production in the absence of herbivores. We also grew offspring in the field to examine reproductive output under natural conditions. Results We found transgenerational effects of herbivory and maternal plant inbreeding on seedling emergence and reproductive output. Offspring of herbivore‐damaged plants had greater emergence, flowered earlier, and produced more flowers and seeds than offspring of undamaged plants. Offspring of outbred maternal plants also had greater seedling emergence and reproductive output than offspring of inbred maternal plants, even though all offspring were outbred. Moreover, the effects of maternal plant inbreeding were more severe when plant offspring were grown in field conditions. Conclusions This study demonstrates that both herbivory and inbreeding have fitness consequences that extend across generations even in outbred progeny. ISSN:1914-2016: ISSN:0002-9122

13 pages, 4 figures, supplementary data https://doi.org/10.1093/molbev/msz153, Domestication of wild animals induces a set of phenotypic characteristics collectively known as the domestication syndrome. However, how this syndrome emerges is still not clear. Recently, the neural crest cell deficit hypothesis proposed that it is generated by a mildly disrupted neural crest cell developmental program, but clear support is lacking due to the difficulties of distinguishing pure domestication effects from preexisting genetic differences between farmed and wild mammals and birds. Here, we use a farmed fish as model to investigate the role of persistent changes in DNA methylation (epimutations) in the process of domestication. We show that early domesticates of sea bass, with no genetic differences with wild counterparts, contain epimutations in tissues with different embryonic origins. About one fifth of epimutations that persist into adulthood are established by the time of gastrulation and affect genes involved in developmental processes that are expressed in embryonic structures, including the neural crest. Some of these genes are differentially expressed in sea bass with lower jaw malformations, a key feature of domestication syndrome. Interestingly, these epimutations significantly overlap with cytosine-to-thymine polymorphisms after 25 years of selective breeding. Furthermore, epimutated genes coincide with genes under positive selection in other domesticates. We argue that the initial stages of domestication include dynamic alterations in DNA methylation of developmental genes that affect the neural crest. Our results indicate a role for epimutations during the beginning of domestication that could be fixed as genetic variants and suggest a conserved molecular process to explain Darwin’s domestication syndrome across vertebrates, Research supported by the Spanish Ministry of Economy and Competitiveness (MINECO) grants “Epifarm” (ref. AGL2013-41047-R) and “Epimark” (ref. AGL2016-78710-R) to F.P. D.A. was supported by a PhD scholarship from the Spanish Government (BES-2011-044860) and an Epimark contract

Human population growth has led to an increased release of chemical contaminants into aquatic environments. Emerging chemical contaminants (ECCs) are of increasing concern because they can affect non-target organisms in aquatic ecosystems. The application of anticancer drugs is increasing because of enhanced cancer rates and use of chemotherapy. We assessed the impacts of two widely used anticancer drugs known for their distinct modes of action, namely 5-fluorouracil (5-FU) and doxorubicin (DOX), on the freshwater rotifer Brachionus calyciflorus across generations. Rotifer mortality (24 h) and population growth (48 h) were assessed to determine initial lethal and sub-lethal effects. Exposure of rotifers to 5-FU (up to 200 mg L−1) did not cause mortality, while DOX caused mortality at high concentrations (EC50 = 15.6 mg L−1). Effects of 5-FU on population growth rate was higher than DOX (5-FU EC50 = 10.49 µg L−1, DOX EC50 = 8.78 mg L−1). The effects of the drugs in binary mixture on population growth rates were dose dependent; significant antagonistic effects were found when 5-FU was present in the mixture at high concentrations. Finally, a transgenerational assay for five generations revealed that rotifers were able to recover their population growth rate after fourth generation when exposed to 5-FU; however, population became non-viable after the second generation of exposure to DOX. At the cellular level, accumulation of reactive oxygen species and plasma membrane damage were observed at EC10 and increased at EC50 for both drugs. After exposure of rotifers to 5-FU across generations, there were signs of oxidative stress recovery, as shown by a decrease in ROS accumulation and plasma membrane damage. Our results showed for the first time that the adverse effects of anticancer drugs on freshwater rotifer populations are drug and dose dependent and can persist or be attenuated along generations.

Coccinella septempunctata (ladybird) is one of the foremost natural predators that feed on aphids. Thus, C. septempunctata serves as an effective biological control agent in integrated pest management (IPM) programs. To supplement the activity of biological control agents, IPM programs often incorporate chemical pesticides to bolster crop protection. To evaluate the effects of a potent insecticide, tolfenpyrad, on C. septempunctata, we tested the sublethal effects of tolfenpyrad on all developmental stages of the life cycle of C. septempunctata and its effects on the next generation. For sublethal testing of the parent generation, the LR50 of tolfenpyrad for C. septempunctata was determined to range from 1.04 to 8.43 g a.i. /hm2 within a set exposure period, while the hazard quotient (HQ) values were above our threshold value of 2 during the entire observation period. These data indicated a potential toxicity risk from tolfenpyrad exposure. The no observed effect application rates (NOERs) of tolfenpyrad on parents (F0) were determined for survival (0.485 g a.i. /hm2), developmental time of pupation (0.242 g a.i. /hm2), and fecundity (0.485 g a.i. /hm2). Application of sublethal doses to unexposed progeny (F1) of exposed parents, prolonged the L1 (1st instar of larvae) and L2 (2nd instar of larvae) stage, while the total longevity, intrinsic rate of increase (r), finite rate of increase (γ), net reproductive rate (R0), and mean generation time (T) were significantly reduced. These results demonstrated the negative influence of sublethal concentrations of tolfenpyrad on C. septempunctata and its persistent effects on subsequent generations.

Hexavalent chromium [Cr(VI)] pollution is one of most serious heavy metal pollutants in the coastal area and posed serious threats to marine organisms and human beings. Many studies have been conducted on its toxicological effects on living organisms from morphological to physiological aspects. However, there are few studies about the transgenerational toxicological of Cr(VI). In this study, we exposed adult marine medaka fishes with Cr(VI) and their offspring with Cr(VI) to examine transgenerational effects of Cr(VI). We found that there were mechanisms such as changing reproduction modes in males to compensate for impacts on the reproduction. There were differences and similarities between the parental effect and the environmental effect, with the former one causing more serious adverse effects on the offspring of Cr(VI)-exposed fish. It was noteworthy that there was an interaction between the parental and offspring treatment which leads to the attenuation of the parental effects on offspring when the offspring also underwent the same treatment. In addition, physiological adaptation has also been observed in fish to improve their fitness. Overall, effects of Cr(VI) on fish and their offspring were studied to pave a way to study the of mechanisms of adaptation.

Tribolium castaneum (Herbst) is an important pest of stored grain, and benzoquinones secreted by this pest are harmful to humans. T. castaneum has developed strong resistance to fumigants, and an ecofriendly alternative for managing T. castaneum is urgently needed. 1-Octen-3-ol is a major volatile compound present in many mushrooms and fungi. In the current study, the direct toxicity and sublethal and transgenerational effects of 1-octen-3-ol on T. castaneum were investigated. Our results showed that 1-octen-3-ol had strong insecticidal activity against all developmental stages of T. castaneum and repelled T. castaneum adults. 1-Octen-3-ol showed negative effects on the development and reproduction of parental T. castaneum and the subsequent generation: LC30 and LC50 treatments significantly decreased the pupa and adult weights, pupation and emergence rates and fecundity of the parental generation. In addition, LC50 treatment shortened the larval and pupal periods. In the unexposed progeny (F1) of 1-octen-3-ol-exposed parents, decreased survival and pupation rates as well as reduced pupa and adult weights were observed under LC30 and LC50 treatments. In addition, a model food-system experiment showed that 1-octen-3-ol at 98 μL/L exhibited an efficacy of 100% after 7 days of fumigation and completely eliminated T. castaneum offspring. Although a higher concentration of 1-octen-3-ol was needed to achieve an efficacy equal to that of the positive control, dichlorvos (DDVP), 1-octen-3-ol promoted the seedling growth of wheat seeds, suggesting that the concentration used was not only acceptable but also beneficial for wheat seeds. Overall, 1-octen-3-ol seems to be a promising candidate for use as a fumigant and repellent against T. castaneum as well as a seed protectant.

Nanotechnology has become one of the fastest growing industries in the current century because nanomaterials (NMs) are present in an ever-expanding range of consumer products increasing the chance of their release into natural environments. In this study, the impacts of two metal nanoparticles (Ag-NPs and CuO-NPs) and their equivalent ionic forms (Ag+ and Cu2+) were assessed on the lentic freshwater rotifer Brachionus calyciflorus and on its ability to adapt and recover through generations. In our study, Ag-NPs and CuO-NPs inhibited the rotifer population growth rate and caused mortality at low concentrations (< 100 μg L-1). Ag-NPs and CuO-NPs decreased in the medium when organisms were present (48 h exposure: 51.1 % and 66.9 %, respectively), similarly Ag+ and Cu2+ also decreased from medium in presence of the organisms (48 h: 35.2 % and 47.3 %, respectively); although the metal concentrations removed from the medium were higher for nanoparticles than metal ions, metal ions showed higher effects then their respective nanoparticle forms. Rotifer populations exposed for 4 generations to the toxicants were able to recover the population growth rate, but some rotifers showed developmental delay and inability to reproduce even after the removal of the toxicants. Intracellular accumulation of reactive oxygen species as well as plasma membrane damage were found in the rotifers at concentrations corresponding to EC10 (Ag-NPs = 1.7 μg L-1, Ag+ = 4.5 μg L-1, CuO-NPs = 46.9 μg L-1, Cu2+ = 35 μg L-1) of the population growth rate. Our results showed, for the first time, that effects of metal nanoparticles and metal ions on rotifer populations may persist along several generations. This should be taken into account when assessing risks of metal nanoparticles in freshwaters., This work was supported by the strategic programme UID/BIA/ 04050/2019 and the Emergemix project (PTDC/BIABMA/30922/2017) funded by national funds through the Portuguese Foundation for Science and Technology (FCT) I.P. and by the European Regional Development Fund (ERDF) through the COMPETE2020 – Programa Operacional Competitividade e Internacionalizaçao. ˜ Nuno Martins (UMINHO/BD/ 24/2016) was also supported by The Doctoral Program in Applied and Environmental Microbiology - NORTE-08-5369-FSE-000060 funded by NORTE2020 through the European Social Fund.

The hypothesis that exposure to certain environmental chemicals during early life stages may disrupt reproduction across multiple non-exposed generations has significant implications for understanding disease etiology and adverse outcomes. We demonstrate here reproductive multi and transgenerational effects, at environmentally relevant levels, of one of the most prescribed human pharmaceuticals, simvastatin, in a keystone species, the amphipod Gammarus locusta. The transgenerational findings has major implications for hazard and risk assessment of pharmaceuticals and other contaminants of emerging concern given that transgenerational effects of environmental chemicals are not addressed in current hazard and risk assessment schemes. Considering that the mevalonate synthesis, one of the key metabolic pathways targeted by simvastatin, is highly conserved among metazoans, these results may also shed light on the potential transgenerational effects of simvastatin on other animals, including humans. This research was funded by COMPETE 2020, Portugal 2020, the European Union through the ERDF and the Portuguese Foundation for Science and Technology – FCT (Transobesogen project – Trans-phyletic obesogenic responses: from epigenetic modules to transgenerational environmental impacts, reference: PTDC/CTA-AMB/31544/2017 – NORTE-01-0145-FEDER-031544). This research was also supported by the National Funds through FCT under the projects (UIDB/04423/2020; UIDP/04423/2020), by the Spanish Agencia Estatal de Investigación (CTM2017-84763-C3-2-R), and by the Galician Council of Culture, Education and Universities (ED431C2017/36), cofounded by ERDF. A PhD grant awarded to Susana Barros (PD/BD/143090/2018) was funded by the FCT SI

International audience; Background : Bisphenol S is an endocrine disruptor exhibiting metabolic disturbances, especially following perinatal exposures. To date, no data are available on the obesogen effects of BPS in a mutligenerational issue.Objectives : We investigated obesogen effects of BPS in a multigenerational study by focusing on body weight, adipose tissue and plasma parameters in male and female mice.Methods : Pregnant C57BL6/J mice were exposed to BPS (1.5 μg/kg bw/day ie a human equivalent dose of 0.12 μg/kg bw/day) by drinking water from gestational day 0 to post natal day 21. All offsprings were fed with a high fat diet during 15 weeks. Body weight was monitored weekly and fat mass was measured before euthanasia. At euthanasia, blood glucose, insuline, triglyceride, cholesterol and no esterified fatty acid plasma levels were determined and gene expressions in visceral adipose tissue were assessed. F1 males and females were mated to obtain the F2 generation. Likewise, the F2 mice were cross-bred to obtain F3. The same analyses were performed.Results : In F1 BPS induced an overweight in male mice associated to lipolysis gene expressions upregulation. In F1 females, dyslipidemia was observed. In F2, BPS exposure was associated to an increase in body weight, fat and VAT masses in males and females. Several plasma parameters were increased but with a sex related pattern (blood glucose, triglycerides and cholesterol in males and NEFA in females). We observed a down-regulation in mRNA expression of gene involved in lipogenesis and in lipolysis for females but only in the lipogenesis for males. In F3, a decrease in VAT mass and an upregulation of lipogenesis gene expression occurred only in females.Conclusions : BPS perinatal exposure induced sex-dependent obesogen multigenerational effects, the F2 generation being the most impacted. Transgenerational disturbances persisted only in females.

International audience; We explore the delayed consequences of parental exposure to environmentally relevant cadmium concentrations on the life-history traits throughout generations of the freshwater crustaceanGammarus fossarum. We report the preliminary results obtained during a challenging one-year laboratory experiment in this environmental species and propose the use of population modeling to interpret the changes in offspring life-history traits regarding their potential demographic impacts. The main outcome of this first long-term transgenerational assay is that the exposure of spawners during a single gametogenesis cycle (3 weeks) could result in severe cascading effects on the life-history traits along three unexposed offspring generations (one year). Indeed, we observed a decrease in F1 reproductive success, an early onset of F2 offspring puberty with reduced investment in egg yolk reserves, and finally a decrease in the growth rate of F3 juveniles. However, the analysis of these major transgenerational effects by means of a Lefkovitch matrix population model revealed only weak demographic impacts. Population compensatory processes mitigating the demographic consequences of parental exposure seem to drive the modification of life-history traits in offspring generations. This exploratory study sheds light on the role of population mechanisms involved in the demographic regulation of the delayed effects of environmental toxicity in wild populations.

Background Although in all sexually reproducing organisms an individual has a mother and a father, non-genetic inheritance has been predominantly studied in mothers. Paternal effects have been far less frequently studied, until recently. In the last 5 years, research on environmentally induced paternal effects has grown rapidly in the number of publications and diversity of topics. Here, we provide an overview of this field using synthesis of evidence (systematic map) and influence (bibliometric analyses). Results We find that motivations for studies into paternal effects are diverse. For example, from the ecological and evolutionary perspective, paternal effects are of interest as facilitators of response to environmental change and mediators of extended heredity. Medical researchers track how paternal pre-fertilization exposures to factors, such as diet or trauma, influence offspring health. Toxicologists look at the effects of toxins. We compare how these three research guilds design experiments in relation to objects of their studies: fathers, mothers and offspring. We highlight examples of research gaps, which, in turn, lead to future avenues of research. Conclusions The literature on paternal effects is large and disparate. Our study helps in fostering connections between areas of knowledge that develop in parallel, but which could benefit from the lateral transfer of concepts and methods.

Dietary restriction (DR) is a well-established intervention to extend lifespan across taxa. Recent studies suggest that DR-driven lifespan extension can be cost-free, calling into question a central tenant of the evolutionary theory of aging. Nevertheless, boosting parental longevity can reduce offspring fitness. Such intergenerational trade-offs are often ignored but can account for the “missing costs” of longevity. Here, we use the nematode Caenorhabditis remanei to test for effects of DR by fasting on fitness of females and their offspring. Females deprived of food for 6 days indeed had increased fecundity, survival, and stress resistance after re-exposure to food compared with their counterparts with constant food access. However, offspring of DR mothers had reduced early and lifetime fecundity, slower growth rate, and smaller body size at sexual maturity. These findings support the direct trade-off between investment in soma and gametes challenging the hypothesis that increased somatic maintenance and impaired reproduction can be decoupled.

DNA methylation is an epigenetic mechanism of particular importance in developmental biology, but methylation also varies along organisms' life cycle. Recent studies have deliberated copper (Cu) exposure induced epigenetic changes in Enchytraeus crypticus, a standard species belonging to one of the most common and important genera of soil invertebrates in many ecosystems. There is however no information on how DNA methylation levels change within the life cycle of this species. We here investigate the global DNA methylation profile along the life cycle of E. crypticus and compare this to the expression of target genes involved in methylation. Results showed that after the lowest DNA methylation level at day 3 (early embryonic stage, blastula) there was an increase by day 7 (organogenesis) after which levels were maintained at days 11, 18 and 25. DNA methyltransferase associated protein 1 (DMPA1) and Methyl Binding Domain 2 (MBD2) gene expression was highest during embryo stages (3 to 7 days), then decreasing (11, 18 days) and finally unregulated in adults (25 days). Hence, we here show that DNA methylation in E. crypticus changes among the different life stages, from cocoons to adults. Such information is a key knowledge to use this endpoint and tool in an ecotoxicology context. This means that it is almost implicit that gene expression levels are age specific for a given stressor. It seems logic to recommend to always compare individuals with the same age between treatments, and to be careful when extrapolating results among life stages. Once, we understand more of these effects we may even be able to predict which life stage is more sensitive to specific stressors. An experimental design that aims to cover epigenetics of stressors in a multigenerational exposure, including transgenerational effects, should ensure the synchronous age of organisms for sampling analysis purposes.

Ionizing radiation is known to cause DNA damage, yet the mechanisms underlying potential transgenerational effects of exposure have been scarcely studied. Previously, we observed effects in offspring of zebrafish exposed to gamma radiation during gametogenesis. Here, we hypothesize that these effects are accompanied by changes of DNA methylation possibly inherited by subsequent generations. We assessed DNA methylation in F1 embryos (5.5 hours post fertilization) with whole genome bisulfite sequencing following parental exposure to 8.7 mGy/h for 27 days and found 5658 differentially methylated regions (DMRs). DMRs were predominantly located at known regulatory regions, such as gene promoters and enhancers. Pathway analysis indicated the involvement of DMRs related to similar pathways found with gene expression analysis, such as development, apoptosis and cancers, which could be linked to previous observed developmental defects and genomic instability in the offspring. Follow up of 19 F1 DMRs in F2 and F3 embryos revealed persistent effects up to the F3 generation at 5 regions. These results indicate that ionizing radiation related effects in offspring can be linked to DNA methylation changes that partly can persist over generations. Monitoring DNA methylation could serve as a biomarker to provide an indication of ancestral exposures to ionizing radiation.

Prenatal treatment with the antiepileptic drug valproic acid (VPA) is associated with a significant risk of somatic anomalies, neurodevelopmental delays, and 7-10× increase in the incidence of autism spectrum disorders (ASD) in children. Rodents exposed to VPA in pregnancy show birth defects, deficits in neurodevelopment, and cognitive/social anomalies resembling those of ASD children. Mechanisms of VPA neurobehavioral toxicity are still unclear but as VPA is a non-selective inhibitor of histone deacetylases, epigenetic modifications are likely involved. This study was aimed to evaluate the transgenerational impact of prenatal VPA exposure on mouse early behavioral development, studying F1, F2, and F3 generations after VPA challenge on gestational day (GD) 10.5. We also analyzed in brain and in peripheral blood mononuclear cells the expression levels of different endogenous retrovirus (ERV) families, potential biomarkers of derailed brain development, since human ERVs have been implicated in the pathogenesis of neurodevelopmental disorders (NDDs) such as ASD. Somatic effects of VPA were evident only in F1 generation and more markedly in the female sex. Across F1 and F2 generations, VPA delayed righting reflex, increased motor activity, and reduced ultrasonic vocalizations. The behavioral changes in F3 are milder though in the same direction. VPA increased expression of most ERVs across the three generations in brain and blood. In utero VPA induced neurodevelopmental alterations more marked in the maternal lineage that persisted also in F3, suggesting ERVs as possible downstream effectors of the VPA epigenetic alterations.

BackgroundMembers of theAnopheles gambiaecomplex breed in clean, sunlit temporary bodies of water. Anthropogenic pollution is, however, altering the breeding sites of the vectors with numerous biological effects. Although the effects of larval metal pollution have previously been examined, this study aims to assess the transgenerational effects of larval metal pollution on the major malaria vectorAn. arabiensis.MethodsTwo laboratory strains ofAn. arabiensis, SENN (insecticide-susceptible) and SENN-DDT (insecticide-resistant), were used in this study. After being bred in water polluted with either cadmium chloride, copper nitrate or lead nitrate, several life history characteristics that can have epidemiological implications (fertility, apoptotic damage to reproductive structures, adult longevity and insecticide tolerance) were examined in the adults and compared to those of adults bred in clean water.ResultsAll metal treatments reduced fecundity in SENN, but only lead treatment reduced fertility in SENN-DDT. Cadmium chloride exposure resulted in apoptosis and deformation of the testes in both strains. After breeding generation F0 in polluted water, F1 larvae bred in clean water showed an increase in longevity in SENN-DDT adult females. In contrast, after breeding the F0 generation in polluted water, longevity was reduced after cadmium and copper exposure in the F1 generation. Larval metal exposure resulted in an increase in insecticide tolerance in adults of the SENN strain, with SENN-DDT adults gaining the greatest fold increase in insecticide tolerance.ConclusionsThis study demonstrates that a single exposure to metal pollution can have transgenerational effects that are not negated by subsequent breeding in clean water.

An insect’s phenotype can be influenced by the experiences of the parental generation. However, the effects of the parental symbiotic microbiome and host plant use on the offspring are unclear. We addressed this gap of knowledge by studying Pieris brassicae, a multivoltine butterfly species feeding on different brassicaceous plants across generations. We investigated how disturbance of the parental bacterial community by antibiotic treatment affects F(1) larval traits. We tested the effects depending on whether F(1) larvae are feeding on the same plant species as their parents or on a different one. The parental treatment alone had no impact on the biomass of F(1) larvae feeding on the parental plant species. However, the parental treatment had a detrimental effect on F(1) larval biomass when F(1) larvae had a different host plant than their parents. This effect was linked to higher larval prophenoloxidase activity and greater downregulation of the major allergen gene (MA), a glucosinolate detoxification gene of P. brassicae. Bacterial abundance in untreated adult parents was high, while it was very low in F(1) larvae from either parental type, and thus unlikely to directly influence larval traits. Our results suggest that transgenerational effects of the parental microbiome on the offspring’s phenotype become evident when the offspring is exposed to a transgenerational host plant shift. IMPORTANCE Resident bacterial communities are almost absent in larvae of butterflies and thus are unlikely to affect their host. In contrast, adult butterflies contain conspicuous amounts of bacteria. While the host plant and immune state of adult parental butterflies are known to affect offspring traits, it has been unclear whether also the parental microbiome imposes direct effects on the offspring. Here, we show that disturbance of the bacterial community in parental butterflies by an antibiotic treatment has a detrimental effect on those offspring larvae feeding on a different host plant than their parents. Hence, the study indicates that disturbance of an insect’s parental microbiome by an antibiotic treatment shapes how the offspring individuals can adjust themselves to a novel host plant.

9 pages, 3 figures, 2 tables, 1 appendix supplementary data, Accumulating evidence shows that environmental changes can affect population sex ratios through epigenetic regulation of gene expression in species where sex depends on both genetic and environmental cues. Sometimes, altered sex ratios persist in the next generation even when the environmental cue is no longer present (a multigenerational effect). However, evidence of transgenerational effects (i.e., beyond the first non-exposed generation), which tend to be paternally transmitted, is scarce and a matter of debate. Here, we used the AB strain of zebrafish, where sex depends on both genetic and environmental influences, to study possible multi- (to the F1) and transgenerational (to the F2) effects of elevated temperature during the critical period of sex differentiation. From eight initial different families, five were selected in order to capture sufficient variation between the sex ratio of the control group (28 °C) and the group exposed to elevated (35 °C) temperature only at the parental (P) generation. Results showed a consistent increase in the proportion of males in the P generation in all five families as a result of heat treatment. Sex ratios were then determined in the F1 and F2 offspring derived from both above groups, which were all raised at 28 °C. A persisting male-skewed sex ratio in the 35°C-derived, unexposed offspring of the F1 generation was observed in three families, denoting family-dependent multigenerational effects. However, no transgenerational effects were observed in the F2 generation of any family. DNA methylation was also assessed in the testis of P, F1 and F2 males derived from exposed and non-exposed fathers and grandfathers. DNA methylation was significantly decreased only in the testis of the 35°C-derived males in the F1 generation but not of the F2 generation and, surprisingly, neither in the 35°C-exposed males of the P generation. Taken together, our results show great interfamily variation, not only in sex ratio response to elevated temperature, but also on its multigenerational effects, denoting a strong influence of genetics. Alterations in the testicular epigenome in F1 males calls for attention to possible, previously unnoticed, effects of temperature in the unexposed offspring of heat-exposed parents in a global warming scenario, This study was supported by the Spanish Ministry of Science and Innovation (MICINN) grant AGL2016-787107-R “Epimark” to FP. AV was supported by Spanish government scholarship BES-2014-069051. LR was supported by MICINN grant AGL2015-73864-JIN. LO was supported by the Frontline Research Excellence Grant KKP126764 of the National Research, Development and Innovation Office of Hungary, With the funding support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S), of the Spanish Research Agency (AEI)

Cerium (Ce, CeCl3) and Erbium (Er, ErCl3) are increasingly used in many electronic devices facilitating the alteration of their biogeochemical cycles (e.g. e-waste). Previous surveys stated that their environmental concentrations due to natural or anthropogenic events can reach up to 161 μg/L in ore mine effluent for Ce with a mean water concentration of 0.79 μg/L, and 11.9 μg/L for Er in ore mine effluents with a mean water concentration of 0.004 μg/L. Their potential effects onto aquatic organisms are still relatively unexplored. In this study, long-term multigenerational effects on Daphnia magna were assessed using various exposure times (3, 7, 14, and 21 days) in three generations (F0, F1 and F2). Each generation was exposed to environmental concentrations of Ce and Er (0.54 and 0.43 μg/L, respectively – mean values) and effects included organisms' size, parental reproduction, and survival, determination of reactive oxygen species (ROS), enzymatic activity (superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST)), gene expression of ATP-binding cassette (ABC) transporter, and uptake. Results evidenced that chronic multi-generational exposure of daphnids to Ce and Er reduced survival, growth and reproduction, decreasing ROS, SOD and CAT from F0 to F2. Ce reduced the number of generated offsprings after each generation, while Er delayed the time of offsprings emergence, but not their number. ROS, SOD, CAT and GST evidenced that Er is slightly more toxic than Ce. Up- and downregulation of genes was limited, but Ce and Er activated the ABC transporters. Uptake of Ce and Er decreased through exposure time and generations.

Endocrine disrupting chemicals (EDCs) include a wide array of pollutants, such as some metals and other toxic elements, which may cause changes in hormonal homeostasis. In addition to affecting physiology of individuals directly, EDCs may alter the transfer of maternal hormones to offspring, i.e. causing trans-generational endocrine disruption. However, such effects have been rarely studied, especially in wild populations. We studied the associations between environmental elemental pollution (As, Cd, Cu, Ni, Pb) and maternally-derived egg thyroid hormones (THs) as well as nestling THs in great tits (Parus major) using extensive sampling of four pairs of polluted and reference populations across Europe (Finland, Belgium, Hungary, Portugal). Previous studies in these populations showed that breeding success, nestling growth and adult and nestling physiology were altered in polluted zones compared to reference zones. We sampled non-incubated eggs to measure maternally-derived egg THs, measured nestling plasma THs and used nestling faeces for assessing local elemental exposure. We also studied whether the effect of elemental pollution on endocrine traits is dependent on calcium (Ca) availability (faecal Ca as a proxy) as low Ca increases toxicity of some elements. Birds in the polluted zones were exposed to markedly higher levels of toxic elements than in reference zones at the populations in Finland, Belgium and Hungary. In contrast to our predictions, we did not find any associations between overall elemental pollution, or individual element concentrations and egg TH and nestling plasma TH levels. However, we found some indication that the effect of metals (Cd and Cu) on egg THs is dependent on Ca availability. In summary, our results suggest that elemental pollution at the studied populations is unlikely to cause overall TH disruption and affect breeding via altered egg or nestling TH levels with the current elemental pollution loads. Associations with Ca availability should be further studied. (C) 2019 Published by Elsevier Ltd.

There are many inputs during development that influence an organism's fit to current or upcoming environments. These include genetic effects, transgenerational epigenetic influences, environmental cues and developmental noise, which are rarely investigated in the same formal framework. We study an analytically tractable evolutionary model, in which cues are integrated to determine mature phenotypes in fluctuating environments. Environmental cues received during development and by the mother as an adult act as detection-based (individually observed) cues. The mother's phenotype and a quantitative genetic effect act as selection-based cues (they correlate with environmental states after selection). We specify when such cues are complementary and tend to be used together, and when using the most informative cue will predominate. Thus, we extend recent analyses of the evolutionary implications of subsets of these effects by providing a general diagnosis of the conditions under which detection and selection-based influences on development are likely to evolve and coexist.

To investigate the transgenerational effects of chronic low-dose-rate internal radiation exposure after the Fukushima Daiichi Nuclear Power Plant accident in Japan, 18 generations of mice were maintained in a radioisotope facility, with free access to drinking water containing (137)CsCl (0 and 100 Bq/ml). The (137)Cs distribution in the organs of the mice was measured after long-term ad libitum intake of the (137)CsCl water. The litter size and the sex ratio of the group ingesting the (137)Cs water were compared with those of the control group, for all 18 generations of mice. No significant difference was noted in the litter size or the sex ratio between the mice in the control group and those in the group ingesting the (137)Cs water. The fixed internal exposure doses were ∼160 Bq/g and 80 Bq/g in the muscles and other organs, respectively.

Environmental contaminants can cause alterations that can be transgenerationally transmitted to subsequent generations. Estrogens are among those contaminants shown to induce heritable changes that persist over generations in mammals. Results in other vertebrates are few. We have analyzed the effects on anxiety of 17α-ethinyl estradiol (EE2) in the F1 and F2 generations in guppies, Poecilia reticulata, obtained from F0 fish maternally exposed to 0 or 20ng/L EE2 until birth. F0 males and females were bred with fish of the same treatment but different families producing F1 offspring. Behavior in the novel tank test at 6months revealed that males with EE2-exposed parents had significantly longer latency to the upper half of the tank than control males, while no EE2 effects were observed in females. Also in F2, obtained from F1 as above, males in the EE2 group had longer latency time compared to control males, with no differences due to EE2-exposure of F0 observed in females. In the scototaxis (light/dark preference) test, latency to first transition to black compartment and total transitions to black were significantly altered in females due to EE2 exposure of F0 while the total time in black was higher in males with EE2-exposed F0 compared with controls. The increased anxiety in the F2 generation demonstrates a transgenerational anxiety phenotype and shows that non-reproductive behavior can be transgenerationally modified by estrogens in fish.

Studies on parental aging are a very attractive field, although it is poorly understood how parental age affects embryonic development and adult traits of the offspring. In this study, we used the turquoise killifish Nothobranchius furzeri, as is the vertebrate with shortest captive lifespan and an interesting model. The embryos of N. furzeri can follow two distinct developmental pathways either entering diapause or proceeding through direct development. Thus, this embryonic plasticity allows this model to be used to study different factors that could affect their embryonic development, including parental age. The first goal of the present study was to investigate whether parental aging could affect the embryo development. To do this, we collected F1 embryos from two breeder groups (old parents and young parents). We monitored the duration of embryonic development and analyzed genes involved in dorsalization process. The second goal was to investigate if embryonic developmental plasticity could be modulated by an epigenetic process. To this end, the expression of DNMTs genes was examined. Our data support the hypothesis that diapause, occurring more frequently in embryos from old parents, is associated with increased expression of DNMT3A and DNMT3B suggesting an epigenetic control. Finally, we analyzed whether parental age could affect metabolism and growth during adult life. Morphometric results and qPCR analysis of genes from IGF system showed a slower growth in adults from old breeders. Moreover, a gender-specificity effect on growth emerged. In conclusion, these results may contribute to the better understanding of the complex mechanism of aging.

Background: Bisphenol A (BPA) is an endocrine disrupting chemical widely used in the manufacture of polycarbonate plastic and epoxy resin to produce a multitude of consumer products, food and drink containers, and medical devices. BPA is similar to estradiol in structure and thus interferes in steroid signalling with different outcomes on reproductive health depending on doses, life stage, mode, and timing of exposure. In this respect, it has an emerging and controversial role as a "reproductive toxicant" capable of inducing short and long-term effects including the modulation of gene expression through epigenetic modification (i.e. methylation of CpG islands, histone modifications and production of non-coding RNA) with direct and trans-generational effects on exposed organisms and their offspring, respectively. Objective: This review provides an overview about BPA effects on reproductive health and aims to summarize the epigenetic effects of BPA in male and female reproduction. Results: BPA exerts epigenetic effects in both male and female reproduction. In males, BPA affects spermatogenesis and sperm quality and possible trans-generational effects on the reproductive ability of the offspring. In females, BPA affects ovary, embryo development, and gamete quality for successful in vivo and in vitro fertilization (IVF). Conclusion: The exact mechanisms of BPA-mediated effects in reproduction are not fully understood; however, the environmental exposure to BPA - especially in fetal and neonatal period - deserves attention to preserve the reproductive ability in both sexes and to reduce the epigenetic risk for the offspring.

Assessing the impact of uranium mining industry on aquatic ecosystems near mining areas is critical to ensure the long-term health and sustainability of ecosystem services. As so, a transgenerational study with Daphnia magna has been conducted to perceive to what extent intermittent discharges of uranium mine effluents into watercourses may impact the DNA integrity and life history traits of cladocerans. Organisms were exposed for 48 h to a 2% dilution of an uranium mine effluent (UME) and to a corresponding dose of waterborne uranium (WU) that, according to our preliminary studies, induces significant DNA damage in daphnids. After exposure, organisms were transferred to clean medium, where three successive generations were monitored for genotoxicity and other effects at the individual and population level. Despite some differences between WU and UME data, our results revealed that the negative impacts of the short-term exposure gradually disappeared after placing the organisms in clean medium. These results suggest that, under intermittent stress, daphnids are able to recover, since after the 3rd brood release, DNA damage (measured as DNA strand breaks) is no longer observed and has no significant impact on the detectable life traits of offspring. Although our results indicate that populations of D. magna are not affected by intermittent and highly diluted discharges from uranium mining, aquatic systems under this kind of pressure should not be seen as hazardous-free. Future studies in this field are recommended and these should consider radionuclides in the water column, their accumulation in the sediments and also multiple life stages.

Parental environment can widely influence offspring phenotype, but paternal effects in the absence of parental care remain poorly understood. We asked if protein content in the larval diet of fathers affected paternity success and gene expression in their sons. We found that males reared on high-protein diet had sons that fared better during sperm competition, suggesting that postcopulatory sexual selection is subject to transgenerational paternal effects. Moreover, immune response genes were downregulated in sons of low-protein fathers, while genes involved in metabolic and reproductive processes were upregulated.

The internal physiological state of a mother can have major effects on her fitness and that of her offspring. We show that maternal effects in the parasitic wasp Eupelmus vuilleti become apparent when old mothers provision their eggs with less protein, sugar and lipid. Feeding from a host after hatching allows the offspring of old mothers to overcome initial shortages in sugars and lipids, but adult offspring of old mothers still emerged with lower protein and glycogen quantities. Reduced egg provisioning by old mothers had adverse consequences for the nutrient composition of adult female offspring, despite larval feeding from a high-quality host. Lower resource availability in adult offspring of old mothers can affect behavioural decisions, life histories and performance. Maternal effects on egg nutrient provisioning may thus affect nutrient availability and fitness of future generations in oviparous animals.

Maternal hormones are important mediators of prenatal maternal effects. Although many experimental studies have demonstrated their potency in shaping offspring phenotypes, we know remarkably little about their adaptive value. Using long-term data on a wild collared flycatcher (Ficedula albicollis) population, we show that natural selection acts in opposite ways on two maternally derived androgens, yolk androstenedione (A4) and yolk testosterone (T). High yolk A4 concentrations are associated with higher fitness, whereas high yolk T concentrations are associated with lower fitness. Natural selection thus favours females that produce eggs with high A4 and low T concentrations. Importantly, however, there exists a positive (non-genetic) correlation between A4 and T, which suggests that females are limited in their ability to reach this adaptive optimum. Thereby, these results provide strong evidence for an adaptive value of differential maternal androgen deposition, and a mechanistic explanation for the maintenance of variation in maternal investment in the wild.

Dioxins are ubiquitous and persistent environmental contaminants whose background levels are still reason for concern. There is mounting evidence from both epidemiological and experimental studies that paternal exposure to the most potent congener of dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), can lower the male/female ratio of offspring. Moreover, in laboratory rodents and zebrafish, TCDD exposure of parent animals has been reported to result in reduced reproductive performance along with other adverse effects in subsequent generations, foremost through the paternal but also via the maternal germline. These impacts have been accompanied by epigenetic alterations in placenta and/or sperm cells, including changes in methylation patterns of imprinted genes. Here, we review recent key studies in this field with an attempt to provide an up-to-date picture of the present state of knowledge to the reader. These studies provide biological plausibility for the potential of dioxin exposure at a critical time-window to induce epigenetic alterations across multiple generations and the significance of aryl hydrocarbon receptor (AHR) in mediating these effects. Currently available data do not allow to accurately estimate the human health implications of these findings, although epidemiological evidence on lowered male/female ratio suggests that this effect may take place at realistic human exposure levels.

Literature on maternal exposures and the risk of epigenetic changes or diseases in the offspring is growing. Paternal contributions are often not considered. However, some animal and epidemiologic studies on various contaminants, nutrition, and lifestyle-related conditions suggest a paternal influence on the offspring's future health. The phenotypic outcomes may have been attributed to DNA damage or mutations, but increasing evidence shows that the inheritance of environmentally induced functional changes of the genome, and related disorders, are (also) driven by epigenetic components. In this essay we suggest the existence of epigenetic windows of susceptibility to environmental insults during sperm development. Changes in DNA methylation, histone modification, and non-coding RNAs are viable mechanistic candidates for a non-genetic transfer of paternal environmental information, from maturing germ cell to zygote. Inclusion of paternal factors in future research will ultimately improve the understanding of transgenerational epigenetic plasticity and health-related effects in future generations.

The ability to learn is ubiquitous in animals but highly variable within and between species, populations and individuals. Diet-related circumstances, such as diet quantity and quality can influence both long-term constitutive (genetic; by selection) and short-term operational (non-genetic; by the immediate circumstances) learning performance. Here, we scrutinized the causes of loss of learning ability, following multi-generational feeding on pollen, in a line of the predatory mite Amblyseius swirskii, which was previously well able to learn prey during early life, enhancing foraging later in life. We investigated whether, and, if so, how quickly, a transgenerational diet switch to live prey restores the early learning ability of foraging predatory mites. The first experiment shows that the early learning ability was restored after switching the diet of the pollen-fed predator line to live spider mites for two generations before conducting the behavioral assay. The second experiment reveals that offspring regained their learning ability if the diet of their mothers was switched from pollen to spider mites for 3 or 10 days before offspring production. Both experiments in concert suggest transgenerational, pollen-induced operational loss of learning ability in the predatory mite A. swirskii. Maternally-transmitted nutrient deficiency and/or maternally-induced epigenetic changes are the most plausible explanations for the pollen diet-induced loss of learning ability. Our study represents a key example for maternal diet-induced variation in learning ability.

[Background] Evidence for the transmission of non-genetic information from father to offspring is rapidly accumulating. While the impact of chemical and physical factors such as toxins or diet on the fitness of the parents and their offspring have been studied extensively, the importance of behavioural and social circumstances has only recently been recognised. Behavioural traits such as personality characteristics can be relatively stable, and partly comprise a genetic component but we know little about the non-genetic transmission of plastic behavioural traits from parents to offspring. We investigated the relative effect of personality and of social dominance as indicators at the opposite ends of the plasticity range on offspring behaviour in the zebrafish (Danio rerio). We assessed male boldness, a behavioural trait that has previously been shown previously to possess genetic underpinnings, and experimentally manipulated male social status to assess the association between the two types of behaviour and their correlation with offspring activity., [Results] We found a clear interaction between the relatively stable and putative genetic effects based on inherited differences in personality and the experimentally induced epigenetic effects from changes in the social status of the father on offspring activity., [Conclusions] Our study shows that offspring behaviour is determined by a combination of paternal personality traits and on-genetic effects derived from the social status of the father., SZ was supported by a grant from the Sven & Lilly Lawski Foundation, JH-R by a grant from the Knut and Alice Wallenberg foundation (102 2013.0072), FZ by a grant from the Wenner-Gren Foundation, and SI by grants from the Swedish Research Council, the European Research Council and the Knut and Alice Wallenberg Foundation.

Background Heroin addiction is a growing concern, affecting the socioeconomic development of many countries. Little is known about transgenerational effects on phenotype changes due to heroin addiction. This study aims to investigate changes in level of anxiety and aggression up to four different generations of adult male rats due to paternal exposure to heroin. Methods Male Sprague–Dawley rats were exposed with heroin intraperitoneally (i.p.) twice-daily for 14 days with increasing dosage regimen (F0-heroin). Male Sprague–Dawley rats (6-weeks-old) were divided into: (1) heroin exposed group (F0-heroin) and (2) control group treated with saline solution (F0-control). The dosage regime started with the lowest dose of 3 mg/kg per day of heroin followed by 1.5 mg/kg increments per day to a final dose of 13.5 mg/kg per day. Offspring were weaned on postnatal day 21. The adult male offspring from each generation were then mated with female-naïve rats after 2 weeks of heroin absence. Open field test and elevated plus maze test were used to study the anxiety level, whereas resident intruder test was used to evaluate aggression level in the addicted male rats and their offspring. Results Heroin exposure in male rats had resulted in smaller sizes of the litters compared to the control. We observed a higher anxiety level in the F1 and F2 progenies sired by the heroin exposed rats (F0) as compared to the control rats. Paternal heroin exposure also caused significantly more aggressive offspring in F1 compared to the control. The same pattern was also observed in the F2. Conclusion Our results demonstrated that the progenies of F1 and F2 sustained higher levels of anxiety and aggression which are due to paternal heroin exposure.

The phenotype of an individual is the result of complex interactions between genotype and current, past and ancestral environment leading to a lifelong remodelling of our epigenomes. The vast majority of common diseases, including atherosclerosis, diabetes, osteoporosis, asthma, neuropsychological and autoimmune diseases, which often take root in early development, display some degree of sex bias, very marked in some cases. This bias could be explained by the role of sex chromosomes, the different regulatory pathways underlying sexual development of most organs and finally, lifelong fluctuating impact of sex hormones. A substantial proportion of dimorphic genes expression might be under the control of sex-specific epigenetic marks. Environmental factors such as social behaviour, nutrition or chemical compounds can influence, in a gender-related manner, these flexible epigenetic marks during particular spatiotemporal windows of life. Thus, finely tuned developmental program aspects, for each sex, may be more sensitive to specific environmental challenges, particularly during developmental programming and gametogenesis, but also throughout the individual's life under the influence of sex steroid hormones and/or sex chromosomes. An unfavourable programming could thus lead to various defects and different susceptibility to diseases between males and females. Recent studies suggest that this epigenetic programming could be sometimes transmitted to subsequent generations in a sex-specific manner and lead to transgenerational effects (TGEs). This review summarizes the current understanding in the field of epigenetic programming and highlights the importance of studying both sexes in epidemiological protocols or dietary interventions both in humans and in experimental animal models.

The seven-spot ladybird beetle, Coccinella septempunctata, is a major natural enemy of aphids in the field and in greenhouses in China and is part of integrated pest management (IPM). Imidacloprid, a highly efficient insecticide that not only kills aphids at lethal concentrations, but also can cause various sublethal effects in nontarget organisms. To strengthen IPM and its sustainability, it is important assessing possible side effects on natural enemies. When the effects of sublethal concentrations (LC5 and 10%LC5) of imidacloprid on C. septempunctata were evaluated, the adult longevity was shortened by 23.97 and 28.68 %, and the fecundity reduced by 52.81 and 56.09 % compared to control population. In the F1 generation (i.e., the progeny of the exposed individuals), the juvenile development was slower by 1.44 days and 0.66 days, and the oviposition period was shortened by 10 and 13 days, respectively. The fecundity of the F1 generation decreased by 17.88, 44.03 and 51.69 % when exposed to 1%LC5, 10%LC5, and LC5, respectively. The results of demographical growth estimates showed that the intrinsic rate of increase (r m ) and net reproductive rate (R 0 ) were lower in C. septempunctata populations that had been exposed to sublethal concentrations of imidacloprid. The results emphasize the importance of assessing side effects of low imidacloprid concentrations on such predator species, even at the transgenerational level.

The parents' phenotype, or the environment they create for their young, can have long-lasting effects on their offspring, with profound evolutionary consequences. Yet, virtually no work has considered how such parental effects might change the adaptive value of behavioural traits expressed by offspring upon reaching adulthood. To address this problem, we combined experiments on burying beetles (Nicrophorus vespilloides) with theoretical modelling and focussed on one adult behavioural trait in particular: the supply of parental care. We manipulated the early-life environment and measured the fitness payoffs associated with the supply of parental care when larvae reached maturity. We found that (1) adults that received low levels of care as larvae were less successful at raising larger broods and suffered greater mortality as a result: they were low-quality parents. Furthermore, (2) high-quality males that raised offspring with low-quality females subsequently suffered greater mortality than brothers of equivalent quality, which reared larvae with higher quality females. Our analyses identify three general ways in which parental effects can change the adaptive value of an adult behavioural trait: by influencing the associated fitness benefits and costs; by consequently changing the evolutionary outcome of social interactions; and by modifying the evolutionarily stable expression of behavioural traits that are themselves parental effects. DOI: http://dx.doi.org/10.7554/eLife.07340.001, eLife digest The burying beetle is an unusual insect in that both the father and the mother take care of their young larvae. They do this by providing food in the form of a small dead animal, such as a mouse, from which they diligently remove any fur or feathers, and by defending both the food and the larvae from rivals. These actions reduce the fitness of the parents, which can be estimated by measuring by how long they survive after caring for their brood. They also increase the health of the larvae, as measured by how large the larvae are when they move away from the carcass to pupate. Kilner et al. wanted to know how the parenting received by larvae affects their behaviour when they grow up and have their own offspring. Larvae were given varying amounts of care, ranging from none at all to five days (which is the typical length of the larval stage for burying beetles). Larvae that received little or no care grew up to become low-quality parents, whereas those that received lots of care became high-quality parents. A low-quality parent is, by definition, a parent that becomes less fit as a result of rearing offspring; a high-quality parent providing the same amount of care would not suffer such a large reduction in its fitness. Each of the female beetles from this first experiment was then mated with a high-quality male and together they took care of their offspring. Kilner et al. observed that the fathers lived longer when they were paired with high-quality mothers than they did when they were paired with lower quality mothers. This happened because the lower quality mothers effectively exploited the fathers, forcing them to do more of the parenting. Although the males gained by raising healthy larvae, they paid a price by dying at a younger age. Results from these insect experiments are not directly linked to human behaviour, but they might tell us why animals of other species are generally so careful to choose a mate that matches them in quality. In this way, they can avoid being exploited when the pair work together to raise young. In future, Kilner et al. will investigate how beetles adjust their parenting effort in response to the effort put in by their partner: can they estimate parental quality directly, or do they simply observe how much care the other partner is providing? DOI: http://dx.doi.org/10.7554/eLife.07340.002

In this review, it is argued that greatly improved understanding ofdomestication may be gained from extending the field of behaviourgenetics to also include epigenetics. Domestication offers aninteresting framework of rapid evolutionary changes caused by welldefinedselection pressures. Behaviour is an important phenotype inthis context, as it represents the primary means of response toenvironmental challenges. An overview is provided of the evidencefor genetic involvement in behavioural control and the presently usedmethods for finding so-called behaviour genes. This shows thatevolutionary changes in behaviour are to a large extent correlated tochanges in patterns of gene expression, which brings epigenetics intothe focus. This area is concerned with the mechanisms controllingthe timing and extent of gene expression, and a lot of focus has beenplaced on methylation of cytosine in promoter regions, usuallyassociated with genetic downregulation. The review considers theavailable evidence that environmental input, for example stress, canmodify methylation and other epigenetic marks and subsequentlyaffect behaviour. Furthermore, several studies are reviewed,demonstrating that acquired epigenetic modifications can be inheritedand cause trans-generational behaviour changes. In conclusion,epigenetics may signify a new paradigm in this respect, as it showsthat genomic modifications can be caused by environmental signals,and random mutations in DNA sequence are therefore not the onlysources of heritable genetic variation. FundingThis review is produced within the framework of the Swedish Center of Excellence in Animal Welfare Science, funded by FORMAS, and the LiU-Neuro network, funded by Linköping University and the county council of Östergötland. It is a part of the European Research Council Advanced Research Grant ‘GENEWELL – Genetics and epigenetics of animal welfare’ (ERC 322206).

19 p.-6 fig., In mammals, germ cell differentiation is initiated in the Primordial Germ Cells (PGCs) during fetal development. Prenatal exposure to environmental toxicants such as endocrine disruptors may alter PGC differentiation, development of the male germline and induce transgenerational epigenetic disorders. The anti-androgenic compound vinclozolin represents a paradigmatic example of molecule causing transgenerational effects on germ cells. We performed prenatal exposure to vinclozolin in mice and analyzed the phenotypic and molecular changes in three successive generations. A reduction in the number of embryonic PGCs and increased rate of apoptotic cells along with decrease of fertility rate in adult males were observed in F1 to F3 generations. Blimp1 is a crucial regulator of PGC differentiation. We show that prenatal exposure to vinclozolin deregulates specific microRNAs in PGCs, such as miR-23b and miR-21, inducing disequilibrium in the Lin28/let-7/Blimp1 pathway in three successive generations of males. As determined by global maps of cytosine methylation, we found no evidence for prominent changes in DNA methylation in PGCs or mature sperm. Our data suggest that embryonic exposure to environmental endocrine disruptors induces transgenerational epigenetic deregulation of expression of microRNAs affecting key regulatory pathways of germ cells differentiation., We thank M. Quesada, O. Barcón and M. Moreno for caring for the animals. We also acknowledged the support from "EpiGeneSys European Network of Excellence".

This study aimed to examine the mechanisms involved in the transgenerational increase in Daphnia magna sensitivity to waterborne depleted uranium (DU) under controlled laboratory conditions. Daphnids were exposed to concentrations ranging from 2 to 50 μg L-1 over two successive generations. Genotoxic effects were assessed using random amplified polymorphic DNA and real time PCR (RAPD-PCR). Effects on life history (survival, fecundity and somatic growth) were monitored from hatching to release of brood 5. Different exposure regimes were tested to investigate the specific sensitivity of various life stages to DU. When daphnids were exposed continuously or from hatching to deposition of brood 5, results demonstrated that DNA damage accumulated in females and were transmitted to offspring in parallel with an increase in severity of effects on life history across generations. When daphnids were exposed during the embryo stage only, DU exposure induced transient DNA damage which was repaired after neonates were returned to a clean medium. Effects on life history remained visible after hatching and did not significantly increase in severity across generations. The present results suggest that DNA damage might be an early indicator of future effects on life history. © 2013 Elsevier Inc.

Background Phenotypic plasticity operates across generations, when the parental environment affects phenotypic expression in the offspring. Recent studies in invertebrates have reported transgenerational plasticity in phenotypic responses of offspring when the mothers had been previously exposed to either live or heat-killed pathogens. Understanding whether this plasticity is adaptive requires a factorial design in which both mothers and their offspring are subjected to either the pathogen challenge or a control, in experimentally matched and mismatched combinations. Most prior studies exploring the capacity for pathogen-mediated transgenerational plasticity have, however, failed to adopt such a design. Furthermore, it is currently poorly understood whether the magnitude or direction of pathogen-mediated transgenerational responses will be sensitive to environmental heterogeneity. Here, we explored the transgenerational consequences of a dual pathogen and stress challenge administered in the maternal generation in the fruit fly, Drosophila melanogaster. Prospective mothers were assigned to a non-infectious pathogen treatment consisting of an injection with heat-killed bacteria or a procedural control, and a stress treatment consisting of sleep deprivation or control. Their daughters and sons were similarly assigned to the same pathogen treatment, prior to measurement of their reproductive success. Results We observed transgenerational interactions involving pathogen treatments of mothers and their offspring, on the reproductive success of daughters but not sons. These interactions were unaffected by sleep deprivation. Conclusions The direction of the transgenerational effects was not consistent with that predicted under a scenario of adaptive transgenerational plasticity. Instead, they were indicative of expectations based on terminal investment. Electronic supplementary material The online version of this article (doi:10.1186/s12862-016-0737-6) contains supplementary material, which is available to authorized users.