DNA methylation 6 mA and histone methylation involved in multi-/trans-generational reproductive effects in Caenorhabditis elegans induced by Atrazine.

Atrazine (ATR), a widely used triazine herbicide, is an environmental endocrine disruptor that can cause health problems. However, whether there are multi/trans-generational reproductive impacts of ATR have not been studied. Therefore, in this study, Caenorhabditis elegans was used as a preferable model organism to identify the multi/trans-generational reproductive toxicity of ATR. Only parental C.elegans (P0) were exposed to different concentrations (0.0004-40 mg/L) for 48 h and the subsequent offspring (F1-F5) were grown under ATR-free conditions and ATR conditions.The results showed that ATR exposure during P0 decreased fecundity, including a reduction in fertilized eggs, oocytes, and ovulation rate, delayed gonadal development, and decreased the relative area of gonad arm and germ cell number. Furthermore, continuous ATR exposure (P0-F5) causes a significant increase in reproductive toxicity in subsequent generations, although no significant toxicity occurred in the P0 generation after exposure to environmental-related concentrations, suggesting that ATR exposure might have cumulative effects. Likewise, parental exposure to ATR caused transgenerational toxicity impairments. Interestingly, only reproductive toxicity, not development toxicity, was transmitted to several generations (F1-F4), and the F2 generation showed the most notable changes. QRT-PCR results showed that genes expression related to DNA methylation 6 mA (damt-1, nmad-1) and histone H3 methylation (mes-4, met-2, set-25, set-2, and utx-1) can also be passed on to offspring. The function of H3K4 and H3K9 methylation were explored by using loss-of-function mutants for set-2, set-25, and met-2. Transmissible reproductive toxicity was absent in met-2(n4256), set-2(ok952), and set-25(n5021) mutants, which suggests that the histone methyltransferases H3K4 and H3K9 activity are indispensable for the transgenerational effect of ATR. Finally, the downstream genes of DNA methylation and histone H3 methylation were determined. ATR upregulated the expression of ZC317.7, hsp-6, and hsp-60. Mitochondrial stress in parental generation dependent transcription 6 mA modifiers may establish these epigenetic marks in progeny.

Evaluating the existence and benefit of major histocompatibility complex-based mate choice in an isolated owl population.

How mate preferences evolve in the first place has been a major conundrum for sexual selection. Some hypotheses explaining this assume fitness benefit derived from subsequent generations. Major histocompatibility complex (MHC)-based mate choice is a representative example of the mate choice that is associated with such trans-generational mechanisms. To provide evidences for fitness benefit of MHC-based mate choice, previous studies assessed the association between own MHC genotype and own fitness components. However, the association between MHC-based mate choice in the parental generation and fitness components in the resultant offspring generation has only rarely been measured in wild populations. Focusing on the isolated population of the monogamous Ryukyu Scops Owl (Otus elegans interpositus) on Minami-daito Island, Japan, we found evidence of MHC-based mate choice. However, we found no evidence of MHC-based mate choice increasing own reproductive success or offspring survival. This is a rare case study that directly examines the existence of the trans-generational indirect benefit of MHC-based mate choice for genetic compatibility from trans-generational data in a wild bird population. By investigating the fitness benefits of mate choice, this study serves to facilitate our understanding of the evolution of MHC-based mate choice.

Transgenerational reproductive and developmental toxicity of tebuconazole in Caenorhabditis elegans.

The transgenerational reproductive and developmental toxicity of tebuconazole (TEB) in Caenorhabditis elegans was investigated over five generations (P0 - F4). Only parental C.elegans (P0) were exposed to TEB (0, 0.01, 0.1, 1, and 10 µg/L) for 24 h and the subsequent offspring (F1-F4) were grown under TEB-free conditions. TEB exposure caused dose-dependent reproductive defects and developmental impairments in C.elegans. In the P0 generation reproductive defects were observed such as: reduced brood size and embryo hatchability, prolonged generation time, retarded gonadal development, and slower germline proliferation, even at 0.01 µg/L, together with developmental toxicity with significant reduced body length and narrowed body width at 10 µg/L. Additionally, the brood size significantly reduced in F2, which began to recover from F3, but was still lower than the control in F4. The proportion of abnormalities increased significantly in F2 and reduced from F3, but was still higher than the control, suggesting that TEB could have cumulative potential and be passed to offspring through parental exposure. Furthermore, exposure to TEB (10 µg/L) in P0 significantly reduced the body length in F1, which began to recover from F2, and was the same level as the control in F4. There was a concentration-dependent increase in body width in F1-F4, with a significant increase only observed in F1 at 10 µg/L. Thus, parental exposure to TEB induced transgenerational defects in both reproduction and development, emphasizing the significance of considering bio-toxicity over multiple generations to conduct accurate assessment of environmental risks of toxicants.

OBSERVING THE INFLUENCE OF MINDFULNESS AND ATTACHMENT STYLES THROUGH MOTHER AND INFANT INTERACTION: A LONGITUDINAL STUDY.

The cross-generational influence of attachment security or insecurity on caregiving is well-established. Recently, research has focused on mindfulness as a potential variable to interrupt the transmission of insecure attachment and disrupt its effect across generations. Thirty-six pregnant female participants completed the Five Facets Mindfulness Questionnaire and Relationship Questionnaire-Clinical Version at 30 weeks' gestation. Following the infant's birth, mothers and their babies participated in a video-recorded feeding session at 7 to 10 weeks' postpartum. It was predicted that a secure attachment style and higher levels of mindfulness measured prenatally would be associated with greater maternal responsiveness postpartum. The hypothesis was supported for both the secure and insecure (fearful and profoundly distrustful) attachment styles. Mindfulness did not mediate the relationship between attachment and maternal distress. The mindfulness subscale Non-Reacting was significantly associated with maternal response to distress. These findings support the role of prenatal mindfulness skills and attachment security for later postnatal maternal sensitivity to baby.

The trans-generation effect during pulsed cadmium exposure: tolerance and induction of hsp70.

Although the importance of pulse exposure has gained ground in recent years, it still needs to be better evaluated and understood. Two successive generations of Daphnia magna were exposed to four concentrations (40, 60, 80 and100µgCdl(-1)) of 6h cadmium (Cd) pulses. The increase of pulsed concentration of parent generation (F0) led to the decrease of EC50 and an increase of 21-day cumulative mortality of the first generation of offspring (F1). The mortality of F1 has a significantly higher level than F0 when they experienced the same pulse. Hsp70 can be induced by Cd pulse and gradually recover to the normal level after exposure. But the sensitivity of hsp70 of F1 was lower than F0 and the response seemingly was not under the control of heredity. Compared to growth, reproduction was more sensitive. The complete risk assessment of pulse exposure should take the response of offspring into account, especially in an ecological or field context.

Characterization and trans-generation dynamics of mitogene pool in the silver carp (Hypophthalmichthys molitrix).

Multicopied mitogenome are prone to mutation during replication often resulting in heteroplasmy. The derived variants in a cell, organ, or an individual animal constitute a mitogene pool. The individual mitogene pool is initiated by a small fraction of the egg mitogene pool. However, the characteristics and relationship between them has not yet been investigated. This study quantitatively analyzed the heteroplasmy landscape, genetic loads, and selection strength of the mitogene pool of egg and hatchling in the silver carp (Hypophthalmichthys molitrix) using high-throughput resequencing. The results showed heteroplasmic sites distribute across the whole mitogenome in both eggs and hatchlings. The dominant substitution was Transversion in eggs and Transition in hatching accounting for 95.23%±2.07% and 85.38%±6.94% of total HP sites, respectively. The total genetic loads were 0.293±0.044 in eggs and 0.228±0.022 in hatchlings (P=0.048). The dN/dS ratio was 58.03±38.98 for eggs and 9.44±3.93 for hatchlings (P=0.037). These results suggest that the mitogenomes were under strong positive selection in eggs with tolerance to variants with deleterious effects, while the selection was positive but much weaker in hatchlings showing marked quality control. Based on these findings, we proposed a trans-generation dynamics model to explain differential development mode of the two mitogene pool between oocyte maturation and ontogenesis of offspring. This study sheds light on significance of mitogene pool for persistence of populations and subsequent integration in ecological studies and conservation practices.

Effects of Parental Dietary Restriction on Offspring Fitness in Drosophila melanogaster.

Dietary restriction (DR) is a well-established strategy to increase lifespan and stress resistance in many eukaryotic species. In addition, individuals fed a restricted diet typically reduce or completely shut down reproduction compared to individuals fed a full diet. Although the parental environment can lead to changes epigenetically in offspring gene expression, little is known about the role of the parental (F0) diet on the fitness of their offspring (F1). This study investigated the lifespan, stress resistance, development, body weight, fecundity, and feeding rate in offspring from parental flies exposed to a full or restricted diet. The offspring flies of the parental DR showed increases in body weight, resistance to various stressors, and lifespan, but the development and fecundity were unaffected. Interestingly, parental DR reduced the feeding rate of their offspring. This study suggests that the effect of DR can extend beyond the exposed individual to their offspring, and it should be considered in both theoretical and empirical studies of senescence.

Parental exposure to famine in early life and child overweight in offspring in Chinese populations.

BACKGROUND: Little is known about the transgenerational effect of nutrition deficiency in early life. This study aimed to evaluate the associations of fetal and childhood exposure to famine of parents with their offspring's risk of overweight during childhood. METHODS: This analysis included a total of 3734 participants of the China Health and Nutrition Survey aged 1-17 years whose fathers and/or mothers were born in 1955-1966. These children were classified into subgroups according to parental famine exposure status (unexposed and exposed) and timing (fetal-exposed and childhood-exposed). Random effects models were applied to evaluate the associations of parental famine exposure with body mass index (BMI) and overweight of offspring. Fractional polynomial functions were adopted to describe trajectories of BMI against age. RESULTS: Compared with children of unexposed parents, there was a lower risk of overweight among offspring of childhood-exposed fathers [OR (95%CI): 0.80 (0.61, 1.04)] or exposed parents [0.84 (0.68, 1.04)], particularly among male offspring, but not among those with exposed mothers only [0.98 (0.65, 1.47)]. For BMI, children with exposed mothers only had a slightly higher BMI [ß(95%CI): 0.17 (-0.15, 0.49)], while those with exposed fathers only had no difference [-0.02 (-0.23, 0.19)] or exposed parents had a slightly lower BMI [-0.17 (-0.33, 0.00)] (p < 0.05 for interaction between maternal and paternal exposures). Stratified analysis showed little heterogeneity between male and female offspring, but the association between paternal childhood exposure to famine and lower overweight risk in offspring was more evident in high (vs low) paternal education group (p for interaction< 0.05). CONCLUSIONS: The transgenerational associations of early-life exposure to famine with lower risks of child overweight may be via the paternal line and differ by the educational levels of parents. Further studies are warranted to confirm the results and reveal the biological mechanisms underlying.

Multi- and trans-generational effects of N-butylpyridium chloride on reproduction, lifespan, and pro/antioxidant status in Caenorhabditis elegans.

Ionic liquids (ILs) became emerging pollutants. Their poor degradation and accumulation in organisms urged studies on the long-term effects and also the underlying mechanisms. Currently, 1-butylpyrinium chloride ([bpyr]Cl) was chosen to represent the pyridine-based ILs. Its multi-generational effects were measured on C. elegans for 14 consecutive generations (F1 to F14), and the trans-generational effects were also measured in the great-grand-children (T3 and T3') of F1 and F14. The multi-generational results from F1 to F14 showed that the effects of [bpyr]Cl on the initial and total reproduction and lifespan showed oscillation between inhibition and stimulation. Notably, hormetic effects on reproduction were observed in F7 to F10. The trans-generational effects in T3 and T3' showed different residual consequences between one generational exposure (F1) and multiple generational exposure (F14). Further biochemical analysis showed that the pro/antioxidant status also showed oscillation between inhibition and stimulation. The oscillation levels were greater in superoxide dismutase (SOD), catalase (CAT) and protein carbonyl content (PC) than those in glutathione peroxidase (GSH-Px), reactive oxygen species (ROS) and hydroxyl radical (OH). The pro/antioxidant status contributed to both multi- and trans-generational effects of [bpyr]Cl. Future studies should pay attentions to the long-term influence of ILs and also epigenetic explanations.

Environmental Factor-Mediated Transgenerational Inheritance of Igf2r Hypomethylation and Pulmonary Allergic Response via Targeting Dendritic Cells.

The developmental origin of allergic diseases has been suggested, but the molecular basis remains enigmatic. Exposure to environmental factors, such as di-(2-ethylhexyl) phthalate (DEHP; a common plasticizer), is suggested to be associated with increased childhood allergic asthma, but the causal relationship and its underlying mechanism remain unknown. This study explored the transgenerational mechanism of DEHP on allergic asthma and dendritic cell (DC) homeostasis through epigenetic modification. In a murine model, ancestral exposure of C57BL/6 mice to low-dose DEHP led to trans-generational promoter hypomethylation of the insulin-like growth factor 2 receptor (Igf2r), concomitant with enhanced Igf2r expression and increased apoptosis prominently in CD8α+ DCs upon ligand stimulation, with consequent reduction in their IL-12 secretion and subsequent T cell-derived IFN-γ, thereby promoting a default Th2-associated pulmonary allergic response. Increased apoptosis was also noted in circulating IGF2Rhigh human DCs. Further, in human placenta, the methylation level at the orthologous IGF2R promoter region was shown to be inversely correlated with the level of maternal DEHP intake. These results support the importance of ancestral phthalate exposure in conferring the trans-generational risk of allergic phenotypes, featuring hypo-methylation of the IGF2R gene and dysregulated DC homeostasis.

The mechanisms of epigenetic inheritance: how diverse are they?

Although epigenetic inheritance (EI) is a rapidly growing field of modern biology, it still has no clear place in fundamental genetic concepts which are traditionally based on the hereditary role of DNA. Moreover, not all mechanisms of EI attract the same attention, with most studies focused on DNA methylation, histone modification, RNA interference and amyloid prionization, but relatively few considering other mechanisms such as stable inhibition of plastid translation. Herein, we discuss all known and some hypothetical mechanisms that can underlie the stable inheritance of phenotypically distinct hereditary factors that lack differences in DNA sequence. These mechanisms include (i) regulation of transcription by DNA methylation, histone modifications, and transcription factors, (ii) RNA splicing, (iii) RNA-mediated post-transcriptional silencing, (iv) organellar translation, (v) protein processing by truncation, (vi) post-translational chemical modifications, (vii) protein folding, and (viii) homologous and non-homologous protein interactions. The breadth of this list suggests that any or almost any regulatory mechanism that participates in gene expression or gene-product functioning, under certain circumstances, may produce EI. Although the modes of EI are highly variable, in many epigenetic systems, stable allelic variants can be distinguished. Irrespective of their nature, all such alleles have an underlying similarity: each is a bimodular hereditary unit, whose features depend on (i) a certain epigenetic mark (epigenetic determinant) in the DNA sequence or its product, and (ii) the DNA sequence itself (DNA determinant; if this is absent, the epigenetic allele fails to perpetuate). Thus, stable allelic epigenetic inheritance (SAEI) does not contradict the hereditary role of DNA, but involves additional molecular mechanisms with no or almost no limitations to their variety.