New insights into how parental worms protect their offspring
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Maternal effects in the model system Daphnia: the ecological past meets the epigenetic future
Maternal effects have been shown to play influential roles in many evolutionary and ecological processes. However, understanding how environmental stimuli induce within-generation responses that transverse across generations remains elusive, particularly when attempting to segregate confounding effects from offspring genotypes. This review synthesizes literature regarding resource- and predation-driven maternal effects in the model system Daphnia, detailing how the maternal generation responds to the environmental stimuli and the maternal effects seen in the offspring generation(s). Our goal is to demonstrate the value of Daphnia as a model system by showing how general principles of maternal effects emerge from studies on this system. By integrating the results across different types of biotic drivers of maternal effects, we identified broadly applicable shared characteristics: 1. Many, but not all, maternal effects involve offspring size, influencing resistance to starvation, infection, predation, and toxins. 2. Maternal effects manifest more strongly when the offspring’s environment is poor. 3. Strong within-generation responses are typically associated with strong across-generation responses. 4. The timing of the maternal stress matters and can raise or lower the magnitude of the effect on the offspring’s phenotype. 5. Embryonic exposure effects could be mistaken for maternal effects. We outline questions to prioritize for future research and discuss the possibilities for integration of ecologically relevant studies of maternal effects in natural populations with the molecular mechanisms that make them possible, specifically by addressing genetic variation and incorporating information on epigenetics. These small crustaceans can unravel how and why non-genetic information gets passed to future generations.
Transgenerational inheritance of diabetes susceptibility in male offspring with maternal androgen exposure
Androgen exposure (AE) poses a profound health threat to women, yet its transgenerational impacts on male descendants remain unclear. Here, employing a large-scale mother-child cohort, we show that maternal hyperandrogenism predisposes sons to β-cell dysfunction. Male offspring mice with prenatal AE exhibited hyperglycemia and glucose intolerance across three generations, which were further exacerbated by aging and a high-fat diet. Mechanistically, compromised insulin secretion underlies this transgenerational susceptibility to diabetes. Integrated analyses of methylome and transcriptome revealed differential DNA methylation of β-cell functional genes in AE-F1 sperm, which was transmitted to AE-F2 islets and further retained in AE-F2 sperm, leading to reduced expression of genes related to insulin secretion, including Pdx1, Irs1, Ptprn2, and Cacna1c. The methylation signatures in AE-F1 sperm were corroborated in diabetic humans and the blood of sons with maternal hyperandrogenism. Moreover, caloric restriction and metformin treatments normalized hyperglycemia in AE-F1 males and blocked their inheritance to offspring by restoring the aberrant sperm DNA methylations. Our findings highlight the transgenerational inheritance of impaired glucose homeostasis in male offspring from maternal AE via DNA methylation changes, providing methylation biomarkers and therapeutic strategies to safeguard future generations’ metabolic health.
Maternal high-fat diet disrupts intestinal mucus barrier of offspring by regulating gut immune receptor LRRC19
Maternal high fat diet (MHFD) increased colitis susceptibility in adulthood. However, the mechanism remains unclear. We sought to explore whether novel gut immune receptor leucine-rich repeat C19 (LRRC19) contributed to the impaired mucus barrier of offspring exposed to MHFD via gut immune response and microbiota. The results showed that MHFD significantly impaired the intestinal mucus barrier of offspring, and up-regulated the expression of LRRC19. Lrrc19 deletion alleviated the mucus barrier disruption. Mechanistically, metagenome sequencing revealed that the MHFD-induced gut microbiota alteration was partly restored in Lrrc19−/− offspring. Muc2-associated bacteria were decreased in the MHFD group, such as Akkermansia_muciniphila_CAG_154, which increased in the Lrrc19-deficient offspring. Moreover, Lrrc19−/− offspring had a higher rate of indole-3-acetic acid (IAA)-producing bacterium, such as Lactobacillus reuteri. A targeted metabolomics analysis revealed that IAA emerged as the top candidate that might mediate the protective effects. IAA was found to improve the mucus barrier function by increasing the ratio of interleukin-22 (IL-22)+ ILC3 cells in an aryl hydrocarbon receptor (AhR)-dependent manner. These results suggest that MHFD disrupts the intestinal mucus barrier of offspring through regulating gut immune receptor LRRC19 and inducing an imbalance of gut microbiota and microbiota-derived metabolites.
Paternal heroin self-administration in rats increases drug-seeking behavior in male offspring via miR-19b downregulation in the nucleus accumbens
Accumulating evidence indicates that drug addiction may lead to adaptive behavioral changes in offspring, potentially due to epigenetic modifications in parental germline. However, the underlying mechanisms remain inadequately understood. In this study, we show that paternal heroin self-administration (SA) increased heroin-seeking behavior in the F1 generation, when compared with offspring sired by yoke-infused control males, indicating cross-generational impact of paternal voluntary heroin seeking behavior. Notably, the increase of heroin seeking behavior in offspring was replicated by zygotic microinjection of sperm RNAs derived from sperm of heroin-SA-experienced rats. Analysis of non-coding RNAs in spermatozoa revealed coordinated changes in miRNA content between the nucleus accumbens and spermatozoa. We validated that restoration of miR-19b downregulation in sperm RNA from self-administration-experienced rats, in parallel with its overexpression in the nucleus accumbens of F1 offspring sired by heroin-SA-experienced fathers, reversed the increased heroin SA observed in these F1 offspring. Taken together, our findings suggest in rats that paternal heroin self-administration induces epigenetic changes in both brain and sperm miRNA, with miR-19b downregulation playing a critical role in mediating the epigenetic inheritance of increased heroin self-administration behavior in the F1 generation.
Molecular mechanism of culinary herb Artemisia argyi in promoting lifespan and stress tolerance
Artemisia argyi Lévl. et Vant. (A. argyi) leaf possesses various health promoting functions contributed by its main bioactive flavonoids. In this study, the anti-aging effect and mechanism of Artemisia argyi leaf extract (AALE) were identified using Caenorhabditis elegans (C. elegans) as a model. The results showed that the AALE promoted the lifespan and stress resistance of C. elegans. It was found that the AALE boosted the expression of oxidative stress-related proteins by regulating the insulin/ IGF-1 signaling (IIS) pathway, which then activated the transcription factors DAF-16/FOXO. The results of RNA-sequence analysis indicated that the changes of genes in nematodes treated with AALE were associated with the responses against oxidative stress, cell maturation, and immune reaction, and stress. The positive results suggest that Artemisia argyi leaf could have the robust benefits for improving healthy aging as well as preventing aging-related diseases in the human body.
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