1,721,006 research outputs found
Influence of maternal diet on the developmental potential of the preimplantation embryo.
No full textThe cleavage-stage embryo is sensitive to environmental conditions that can change developmental potential, leading to altered fetal and postnatal phenotype. We have developed mouse and rat models in vivo to investigate the effect of a mild form of maternal protein undernutrition exclusively during egg cleavage on long-term developmental potential. Maternal low-protein diet (LPD) during embryonic development leads to significant alteration in fetal and postnatal growth, a sustained increase in systolic blood pressure during adult life, and a changed pattern of anxiety-related behavior compared with controls fed a normal-protein diet during the embryonic period. This long-term patterning of phenotype includes gender-specific components. The sensitivity of embryos in vivo is paralleled by a similar adverse programming of phenotype in response to in vitro culture conditions, demonstrated in several species. Given the health care implications of the data arising from these models, elucidation of underlying mechanisms contributing to environment-induced changes in embryo potential is essential. Studies to date indicate that complex interactions are mediated through altered cell signaling, homeostatic regulation, proliferation, and epigenetics. In vivo programming via maternal LPD may initiate through abnormal cross-talk between maternal and embryonic cells involving amino acid and growth factor signaling, which may lead to altered setting of metabolism and biosynthesis within the embryo. Our data further indicate that in response to poor maternal periconceptional nutrition, the embryo can induce adaptations in nutrient supply during later development via the visceral yolk sac to protect fetal growth. However, such adaptations can be inappropriate and contribute to adverse fetal and postnatal programming when maternal nutrient levels exceed those predicted. Epigenetic changes involving DNA methylation in control regions of growth- and metabolism-regulating genes, including imprinted genes, have been identified in response to embryo in vitro culture conditions and sustained maternal LPD during gestation, representing additional mechanisms contributing to changes in developmental potentia
Maternal diet, oocyte nutrition and metabolism and offspring health
No full textMalnutrition (i.e. undernutrition and overnutrition) is a world-wide phenomenon that can affect mammalian oocyte developmental competence following fertilization, compromising the establishment of pregnancy. However, live birth is usually possible during maternal malnutrition even in extremes cases of undernutrition (i.e. anorexia nervosa) and overnutrition (i.e. morbid obesity). Several epidemiological and clinical studies in humans and experimental animal models have demonstrated that in utero development under nutritional stress can program the development of non-communicable diseases (NCD) in adult life (e.g. diabetes, metabolic syndrome). Of further significance is the fact that malnutrition can also program the development of NCD in adulthood via changes on oocyte physiology before conception. This chapter focuses on the available evidence supporting this latter hypothesi
Junctional complexes in the early mammalian embryo
No full textPreimplantation embryos generate intercellular junctions during differentiation of the trophectoderm epithelium and the formation of the blastocyst. These membrane complexes comprise gap junctions, adherens junctions, tight junctions, and desmosomes, each performing fundamental roles in cellular communication, adhesion, and differentiation. The mouse embryo has been used as a model for the biogenesis of cell junctions. Their construction is achieved by temporally regulated gene expression programs. Mechanisms of junction membrane assembly include the timing of transcription, translation, and posttranslational modifications of specific junctional proteins. Human embryos exhibit similar expression programs, and defects in these programs may contribute to reduced embryo viability
Expression of Wnt genes during mouse preimplantation development
No full textPattern formation in the mouse preimplantation embryo is tightly regulated and essential for successful development. Wnt genes are known to regulate cell interactions and cell fate in invertebrates and vertebrates and, therefore, may play a role in the specification of cell lineages and cellular interactions that occur in preimplantation development. Using degenerate primers based on conserved protein sequences in Wnt coding regions, we have found evidence for Wnt gene expression at the blastocyst stage of mouse preimplantation development. We have identified sequences encoding Wnts3a and 4 and confirmed that these are present as transcripts in early development by using reverse transcriptase-polymerase chain reaction (RT-PCR) with specific primers located in the 5' half of these Wnt genes. Studies on the timing of expression showed that Wnt3a transcripts were present in 2-cell embryos which may represent maternally or embryonically derived transcripts since the major transition of maternal to zygotic gene expression occurs during the late 2-cell stage. Both Wnt3a and 4 transcripts were detected in some precompact 4/8-cell stages with consistent expression detected in all compact 8-, 16-cell and blastocyst stages. To our knowledge, expression of Wnt genes has not been previously described at such an early stage of mammalian development.<br/
Cell adhesion in the preimplantation mammalian embryo and its role in trophectoderm differentiation and blastocyst morphogenesis
No full textCell adhesion plays a critical role in the differentiation of the trophectoderm epithelium and the morphogenesis of the blastocyst. In the mouse embryo, E-cadherin mediated adhesion initiates at compaction at the 8-cell stage, regulated post-translationally via protein kinase C and other signalling molecules. E-cadherin adhesion organises epithelial polarisation of blastomeres at compaction. Subsequently, the proteins of the epithelial tight junction are expressed and assemble at the apicolateral contact region between outer blastomeres in three phases, culminating at the 32-cell stage when blastocoel cavitation begins. Cell adhesion events also coordinate the cellular allocation and spatial segregation of the inner cell mass (ICM) of the blastocyst, and the maintenance of epithelial (trophectoderm) and non-epithelial (ICM) phenotypes during early morphogenesis
Support for Barker hypothesis upheld in rat model of maternal undernutrition during the preimplantation period: application of integrated 'random effects' statistical model
No full textIn response to a recent paper published in Reproductive BioMedicine Online by Walters and Edwards (2003), this study reports the application of a random effects regression analysis for evaluation of integrated data involving maternal and embryo/offspring components. Using this method, it is possible to confirm the conclusions of an earlier study that rat maternal undernutrition during the preimplantation period results in blastocyst cell number reduction and postnatal outcomes, including altered growth rates and elevated blood pressure
Statistical analysis of data in support of the Barker hypothesis, advantages of using random effects regression model in hierarchical data
No full textIn a recent note by Walters and Edwards (2004), the authors argued that summary statistics should be used in analysing hierarchical data from our earlier analysis of a rat model of developmental programming and the Barker hypothesis (Kwong et al., 2000, 2004). We reiterate here why such a view is inappropriate. Hierarchical data merits multilevel analysis using a 'random effects' model to enable estimation of variances at different levels and easy assessment of other parameters in a complex data structure
Mismatched prenatal and post-weaning diets lead to sex-specific increases in fat deposition efficiency and exacerbates cardiovascular dysfunction in adult mouse offspring
No full textNutrition of females during the peri-conceptional period and effects on foetal programming and health of offspring
No full textThe period around the time of conception is one characterised by considerable cytological and molecular restructuring as ovulation occurs, the oocyte is fertilised and the embryonic developmental programme begins. The intrinsic processes regulating peri-conceptional progression are supplemented by environmental factors, which contribute important metabolic information that influences several aspects of the developmental programme. Indeed, there is growing evidence from different mammalian animal models, reviewed here, that the peri-conceptional environment mediated through maternal nutrition can modify development throughout gestation and affect the physiological and metabolic health of adult offspring. The concept that adult disease risk may owe its origin to the quality of peri-conceptional maternal nutrition is one, which merits further research for mechanistic understanding and devising preventive strategies.<br/
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