Regulatory Mechanisms Mediated by DNA methyltransferase 1 link the maternal Environment with the Development of the Embryo
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE98851 | GEO | 2018/02/18
REPOSITORIES: GEO
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Project description:During maturation oocytes undergo a recently discovered mitochondrial proteome remodeling event in flies1, frogs1, and humans2. This oocyte mitochondrial remodeling, which includes substantial changes in electron transport chain (ETC) subunit abundance1,2, is regulated by maternal insulin signaling1. Why oocytes undergo mitochondrial remodeling is unknown, with some speculating that it might be an evolutionarily conserved mechanism to protect oocytes from genotoxic damage by reactive oxygen species (ROS)2. In Caenorhabditis elegans, we previously found that maternal exposure to osmotic stress drives a 50-fold increase in offspring survival in response to future osmotic stress3. Like mitochondrial remodeling, we found that this intergenerational adaptation is also regulated by insulin signaling to oocytes3. Here, we used proteomics and genetic manipulations to show that insulin signaling to oocytes regulates offspring's ability to adapt to future stress via a mechanism that depends on ETC composition in maternal oocytes. Specifically, we found that maternally expressed mutant alleles of nduf-7 (complex I subunit) or isp-1 (complex III subunit) altered offspring's response to osmotic stress at hatching independently of offspring genotype. Furthermore, we found that expressing wild-type isp-1 in germ cells (oocytes) was sufficient to restore offspring's normal response to osmotic stress. Chemical mutagenesis screens revealed that maternal ETC composition regulates offspring's response to stress by altering AMP kinase function in offspring which in turn regulates both ATP and glycerol metabolism in response to continued osmotic stress. To our knowledge, these data are the first to show that proper oocyte ETC composition is required to link a mother's environment to adaptive changes in offspring metabolism. The data also raise the possibility that the reason diverse animals exhibit insulin regulated remodeling of oocyte mitochondria is to tailor offspring metabolism to best match the environment of their mother.
| S-EPMC10996803 | biostudies-literature
Project description:Oocytes undergo a recently discovered mitochondrial proteome remodeling event in flies1, frogs1, and humans2. This oocyte mitochondrial remodeling event, which includes substantial changes in electron transport chain (ETC) subunit abundance1,2, is regulated by maternal insulin signaling1. However, why oocytes undergo mitochondrial remodeling is unknown, with some speculating that it might be a conserved mechanism to protect oocytes from genotoxic damage by reactive oxygen species (ROS)2. In Caenorhabditis elegans, we previously found that maternal exposure to osmotic stress drives a 50-fold increase in offspring survival in response to future osmotic stress, and that this intergenerational adaptation is regulated by insulin signaling to oocytes3. Here, we used proteomics and genetic manipulations to show that insulin signaling to oocytes regulates offspring’s ability to adapt to future stress via a mechanism that depends on ETC composition in maternal germ cells/oocytes. Specifically, we found that maternally expressed mutant alleles of nduf-7 (complex I subunit) or isp-1 (complex III subunit) altered offspring’s response to osmotic stress at hatching independently of offspring genotype. Furthermore, we found that expressing wild-type isp-1 in maternal germ cells (oocytes) was sufficient to restore offspring’s normal response to osmotic stress. Chemical mutagenesis screens revealed that oocyte ETC composition regulates offspring’s response to osmotic stress by altering AMP kinase function in offspring which in turn regulates both ATP and glycerol metabolism in offspring in response to continued osmotic stress. To our knowledge, these data are the first to show that changes in oocyte mitochondrial ETC composition can affect an animal phenotype that manifests after embryonic development is complete. The data also suggest that the reason diverse animals exhibit insulin regulated remodeling of oocyte mitochondria might be to tailor offspring metabolism to best match the environment of their mother.
2024-03-09 | GSE261225 | GEO
Project description:A female's behavioral and physiological response to her environment can have lasting effects on the development of her offspring. This type of non-genetic inheritance (or maternal effect) occurs across taxa but is particularly well-studied in birds due to the relative ease of measuring maternal hormones in externally developing eggs. For example, females breeding in areas of high social competition allocate more of the hormone testosterone (T) to their egg yolks. These high-T offspring exhibit numerous phenotypic changes, including faster juvenile growth and enhanced aggression well into adulthood, which are potentially beneficial traits in high-competition areas. Thus, females may be able to communicate the current social environment to their offspring and prepare them for adverse conditions. Yet, the proximate mechanisms underlying how maternal hormones affect offspring are largely ignored, impairing our understanding of an ecologically important source of phenotypic plasticity. Here, we explored the effects of the maternal social environment on yolk T allocation and genome-wide patterns of neural gene expression in male and female tree swallow (Tachycineta bicolor) embryos. We observed a population of free-living tree swallows breeding at sites with variable breeding densities. We performed behavioral observations to record the rate of physical aggression at these sites, which was significantly higher at high density sites. We collected eggs at two developmental timepoints: the day laid to measure maternally derived T concentrations and embryonic day 11 (ED11) to measure gene expression patterns in whole brains using RNA-seq. We took a genome-wide approach to help clarify the potentially diverse mechanisms regulated by early T exposure across variable social environments. We additionally molecularly sexed the embryos to explore sex-specific effects.
2024-10-27 | GSE246544 | GEO
Project description:Oocyte mitochondria link maternal environment to offspring phenotype in C. elegans
| PRJNA1085779 | ENA
Project description:Understanding the interplay between environmental conditions and phenotypes is a fundamental goal of biology. Unfortunately, data that include observations on phenotype and environment are highly heterogeneous and thus difficult to find and integrate. One approach that is likely to improve the status quo involves the use of ontologies to standardize and link data about phenotypes and environments. Specifying and linking data through ontologies will allow researchers to increase the scope and flexibility of large-scale analyses aided by modern computing methods. Investments in this area would advance diverse fields such as ecology, phylogenetics, and conservation biology. While several biological ontologies are well-developed, using them to link phenotypes and environments is rare because of gaps in ontological coverage and limits to interoperability among ontologies and disciplines. In this manuscript, we present (1) use cases from diverse disciplines to illustrate questions that could be answered more efficiently using a robust linkage between phenotypes and environments, (2) two proof-of-concept analyses that show the value of linking phenotypes to environments in fishes and amphibians, and (3) two proposed example data models for linking phenotypes and environments using the extensible observation ontology (OBOE) and the Biological Collections Ontology (BCO); these provide a starting point for the development of a data model linking phenotypes and environments.
| S-EPMC4690371 | biostudies-literature
Project description:Embryo-maternal crosstalk is an important event that involves many biological processes, which must occur perfectly for pregnancy success. This complex communication starts from the zygote stage within the oviduct and continues in the uterus up to the end of pregnancy. Small extracellular vesicles (EVs) are part of this communication and carry bioactive molecules such as proteins, lipids, mRNA, and miRNA. Small EVs are present in the oviductal and uterine fluid and have important functions during fertilization and early embryonic development. Embryonic cells are able to uptake oviductal and endometrium-derived small EVs. Conversely, embryo-derived EVs might modulate oviductal and uterine function. In this review, our aim is to demonstrate the role of extracellular vesicles modulating embryo-maternal interactions during early pregnancy.
| S-EPMC7037557 | biostudies-literature
Project description:BackgroundDespite many improvements with in vitro culture systems, the quality and developmental ability of mammalian embryos produced in vitro are still lower than their in vivo counterparts. Though previous studies have evidenced differences in gene expression between in vivo- and in vitro-derived bovine embryos, there is no comparison at the protein expression level.ResultsA total of 38 pools of grade-1 quality bovine embryos at the 4-6 cell, 8-12 cell, morula, compact morula, and blastocyst stages developed either in vivo or in vitro were analyzed by nano-liquid chromatography coupled with label-free quantitative mass spectrometry, allowing for the identification of 3,028 proteins. Multivariate analysis of quantified proteins showed a clear separation of embryo pools according to their in vivo or in vitro origin at all stages. Three clusters of differentially abundant proteins (DAPs) were evidenced according to embryo origin, including 463 proteins more abundant in vivo than in vitro across development and 314 and 222 proteins more abundant in vitro than in vivo before and after the morula stage, respectively. The functional analysis of proteins found more abundant in vivo showed an enrichment in carbohydrate metabolism and cytoplasmic cellular components. Proteins found more abundant in vitro before the morula stage were mostly localized in mitochondrial matrix and involved in ATP-dependent activity, while those overabundant after the morula stage were mostly localized in the ribonucleoprotein complex and involved in protein synthesis. Oviductin and other oviductal proteins, previously shown to interact with early embryos, were among the most overabundant proteins after in vivo development.ConclusionsThe maternal environment led to higher degradation of mitochondrial proteins at early developmental stages, lower abundance of proteins involved in protein synthesis at the time of embryonic genome activation, and a global upregulation of carbohydrate metabolic pathways compared to in vitro production. Furthermore, embryos developed in vivo internalized large amounts of oviductin and other proteins probably originated in the oviduct as soon as the 4-6 cell stage. These data provide new insight into the molecular contribution of the mother to the developmental ability of early embryos and will help design better in vitro culture systems.
| S-EPMC9764490 | biostudies-literature
Project description:We have previously shown that an increase in intracellular Ca2+ is both necessary and sufficient to commit ectoderm to a neural fate in Xenopus embryos. However, the relationship between this Ca2+ increase and the expression of early neural genes has yet to be defined. Using a subtractive cDNA library between untreated and caffeine-treated animal caps, i.e., control ectoderm and ectoderm induced toward a neural fate by a release of Ca2+, we have isolated the arginine N-methyltransferase, xPRMT1b, a Ca2+-induced target gene, which plays a pivotal role in this process. First, we show in embryo and in animal cap that xPRMT1b expression is Ca2+-regulated. Second, overexpression of xPRMT1b induces the expression of early neural genes such as Zic3. Finally, in the whole embryo, antisense approach with morpholino oligonucleotide against xPRMT1b impairs neural development and in animal caps blocks the expression of neural markers induced by a release of internal Ca2+. Our results implicate an instructive role of an enzyme, an arginine methyltransferase protein, in the embryonic choice of determination between epidermal and neural fate. The results presented provide insights by which a Ca2+ increase induces neural fate.
| S-EPMC1257693 | biostudies-literature
Project description:The proteostasis network is regulated by transcellular communication to promote health and fitness in metazoans. In Caenorhabditis elegans, signals from the germline initiate the decline of proteostasis and repression of cell stress responses at reproductive maturity, indicating that commitment to reproduction is detrimental to somatic health. Here we show that proteostasis and stress resilience are also regulated by embryo-to-mother communication in reproductive adults. To identify genes that act directly in the reproductive system to regulate somatic proteostasis, we performed a tissue targeted genetic screen for germline modifiers of polyglutamine aggregation in muscle cells. We found that inhibiting the formation of the extracellular vitelline layer of the fertilized embryo inside the uterus suppresses aggregation, improves stress resilience in an HSF-1-dependent manner, and restores the heat-shock response in the somatic tissues of the parent. This pathway relies on DAF-16/FOXO activation in vulval tissues to maintain stress resilience in the mother, suggesting that the integrity of the embryo is monitored by the vulva to detect damage and initiate an organismal protective response. Our findings reveal a previously undescribed transcellular pathway that links the integrity of the developing progeny to proteostasis regulation in the parent.
| S-EPMC7197353 | biostudies-literature
Project description:Iron disorders are associated with adverse pregnancy outcomes, yet iron homeostatic mechanisms during pregnancy are poorly understood. In humans and rodents, the iron-regulatory hormone hepcidin is profoundly decreased in pregnant mothers, which is thought to ensure adequate iron availability for transfer across placenta. However, the fetal liver also produces hepcidin, which may regulate fetal iron endowment by controlling placental iron export. To determine the relative contribution of maternal vs embryo hepcidin to the control of embryo iron endowment in iron-sufficient or iron-overloaded mice, we generated combinations of mothers and embryos that had or lacked hepcidin. We found that maternal, but not embryonic, hepcidin determined embryo and placental iron endowment in a healthy pregnancy. We further determined that inflammation can counteract pregnancy-dependent suppression of maternal hepcidin. To establish how essential maternal hepcidin suppression is for embryo iron homeostasis, we mimicked the range of maternal hepcidin activity by administering a hepcidin peptide mimetic to pregnant mice. This also allowed us to determine the effect of isolated maternal hepcidin excess on pregnancy, in the absence of other confounding effects of inflammation. Higher doses of hepcidin agonist caused maternal iron restriction and anemia, lower placenta and embryo weight, embryo anemia, and increased embryo mortality. Low agonist doses did not cause maternal anemia but still adversely affected the embryo, causing anemia, tissue iron deficiency (including in the brain), and decreased weight. Our studies demonstrate that suppression of maternal hepcidin during pregnancy is essential for maternal and embryo iron homeostasis and health.
| S-EPMC7645983 | biostudies-literature