Preimplantation trophectoderm: A 'quick-fix' protector for embryo survival?

The trophectoderm (TE) epithelium forms the outer layer of the mammalian blastocyst and generates the blastocoel through vectorial transport. Its differentiation during cleavage, studied mainly in mouse, is integrated with blastocyst morphogenesis with key roles for cell polarisation, asymmetric cell divisions, cell signalling, regulatory transcription factors and cellular inheritance. The TE provides a physical and cellular protection to the emerging lineages of the embryo essential for the integrity of blastocyst development.

Cultivating a Science, Technology, Engineering and Mathematics (STEM) community for two-year college student success and persistence.

Undergraduate students studying Science, Technology, Engineering and Mathematics (STEM) often fail to persist in critical "gateway" courses, resulting in students leaving the STEM pathway. Community college students leave STEM pathways at higher rates than students at universities. Implementation of a program designed to engage community college STEM students and faculty in a community of support was associated with increased persistence in STEM gateway courses and associate degree completion.

The mammalian preimplantation embryo: Its role in the environmental programming of postnatal health and performance.

During formation of the preimplantation embryo several cellular and molecular milestones take place, making the few cells forming the early embryo vulnerable to environmental stressors than can impair epigenetic reprogramming and controls of gene expression. Although these molecular alterations can result in embryonic death, a significant developmental plasticity is present in the preimplantation embryo that promotes full-term pregnancy. Prenatal epigenetic modifications are inherited during mitosis and can perpetuate specific phenotypes during early postnatal development and adulthood.

Preimplantation or gestation/lactation high-fat diet alters adult offspring metabolism and neurogenesis.

Poor maternal nutrition during pregnancy is known to impair fetal development. Moreover, the preimplantation period is vulnerable to adverse programming of disease. Here, we investigated the effect of a mouse maternal high-fat diet in healthy non-obese dams during preimplantation or throughout pregnancy and lactation on metabolism-related parameters and hippocampal neurogenesis in adult offspring.

Maternal Undernutrition Induces Cell Signalling and Metabolic Dysfunction in Undifferentiated Mouse Embryonic Stem Cells.

Peri-conceptional environment can induce permanent changes in embryo phenotype which alter development and associate with later disease susceptibility. Thus, mouse maternal low protein diet (LPD) fed exclusively during preimplantation is sufficient to lead to cardiovascular, metabolic and neurological dysfunction in adult offspring. Embryonic stem cell (ESC) lines were generated from LPD and control NPD C57BL/6 blastocysts and characterised by transcriptomics, metabolomics, bioinformatics and molecular/cellular studies to assess early potential mechanisms in dietary environmental programming.

Environmental Exposures around Conception: Developmental Pathways Leading to Lifetime Disease Risk.

Environment around conception can influence the developmental programme with lasting effects on gestational and postnatal phenotype and with consequences for adult health and disease risk. Peri-conception exposure comprises a crucial part of the 'Developmental Origins of Health and Disease' (DOHaD) concept. In this review, we consider the effects of maternal undernutrition experienced during the peri-conception period in select human models and in a mouse experimental model of protein restriction.

Blastocyst trophectoderm endocytic activation, a marker of adverse developmental programming.

The mouse preimplantation embryo is sensitive to its environment, including maternal dietary protein restriction, which can alter the developmental programme and affect lifetime health. Previously, we have shown maternal low-protein diet (LPD) causes a reduction in blastocyst mTORC1 signalling coinciding with reduced availability of branched-chain amino acids (BCAAs) in surrounding uterine fluid. BCAA deficiency leads to increased endocytosis and lysosome biogenesis in blastocyst trophectoderm (TE), a response to promote compensatory histotrophic nutrition.

Advanced maternal age perturbs mouse embryo development and alters the phenotype of derived embryonic stem cells.

Advanced maternal age (AMA) is known to reduce fertility, increases aneuploidy in oocytes and early embryos and leads to adverse developmental consequences which may associate with offspring lifetime health risks. However, investigating underlying effects of AMA on embryo developmental potential is confounded by the inherent senescence present in maternal body systems further affecting reproductive success. Here, we describe a new model for the analysis of early developmental mechanisms underlying AMA by the derivation and characterisation of mouse embryonic stem cell (mESC-like) lines from naturally conceived embryos.

Using a Wearable Activity Monitor to Accurately Measure Mobility After Surgery for Hip Fractures (MASH)-A Feasibility Study Protocol.

Introduction: Hip fractures are the most common reason for acute orthopaedic admission in the United Kingdom (UK) and pose a substantial cost to the National Health Service (NHS). A significant proportion of this expenditure is accounted for by hospital bed days, with additional contributions from health and social aftercare. Early ambulation following hip fracture surgery improves outcomes by accelerating functional recovery and reducing the need for ongoing care.

The duration of embryo culture after mouse IVF differentially affects cardiovascular and metabolic health in male offspring.

Study Question: Do the long-term health outcomes following IVF differ depending upon the duration of embryo culture before transfer?

Summary Answer: Using a mouse model, we demonstrate that in male but not female offspring, adverse cardiovascular (CV) health was more likely with prolonged culture to the blastocyst stage, but metabolic dysfunction was more likely if embryo transfer (ET) occurred at the early cleavage stage.

What Is Known Already: ART associate with increased risk of adverse CV and metabolic health in offspring, and these findings have been confirmed in animal models in the absence of parental infertility issues. It is unclear which specific ART treatments may cause these risks.

Periconception maternal low-protein diet adversely affects male mouse fetal bone growth and mineral density quality in late gestation.

Adverse programming of adult non-communicable disease can be induced by poor maternal nutrition during pregnancy and the periconception period has been identified as a vulnerable period. In the current study, we used a mouse maternal low-protein diet fed either for the duration of pregnancy (LPD) or exclusively during the preimplantation period (Emb-LPD) with control nutrition provided thereafter and postnatally to investigate effects on fetal bone development and quality. This model has been shown previously to induce cardiometabolic and neurological disease phenotypes in offspring.

RW-2018-Research Workshop: The Effect of Nutrition on Epigenetic Status, Growth, and Health.

The goal of the 2018 American Society for Parenteral and Enteral Nutrition (ASPEN) Research Workshop was to explore the influence of nutrition and dietary exposure to xenobiotics on the epigenome during critical periods in development and how these exposures influence both disease incidence and severity transgenerationally. A growing compendium of research indicates that the incidence and severity of common and costly human diseases may be influenced by dietary exposures and deficiencies that modify the epigenome. The greatest periods of vulnerability to these exposures are the periconception period and early childhood.

Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory.

Maternal protein malnutrition throughout pregnancy and lactation compromises brain development in late gestation and after birth, affecting structural, biochemical, and pathway dynamics with lasting consequences for motor and cognitive function. However, the importance of nutrition during the preimplantation period for brain development is unknown. We have previously shown that maternal low-protein diet (LPD) confined to the preimplantation period (Emb-LPD) in mice, with normal nutrition thereafter, is sufficient to induce cardiometabolic and locomotory behavioral abnormalities in adult offspring.

Origins of lifetime health around the time of conception: causes and consequences.

Parental environmental factors, including diet, body composition, metabolism, and stress, affect the health and chronic disease risk of people throughout their lives, as captured in the Developmental Origins of Health and Disease concept. Research across the epidemiological, clinical, and basic science fields has identified the period around conception as being crucial for the processes mediating parental influences on the health of the next generation. During this time, from the maturation of gametes through to early embryonic development, parental lifestyle can adversely influence long-term risks of offspring cardiovascular, metabolic, immune, and neurological morbidities, often termed developmental programming.

Insulin and branched-chain amino acid depletion during mouse preimplantation embryo culture programmes body weight gain and raised blood pressure during early postnatal life.

Mouse maternal low protein diet exclusively during preimplantation development (Emb-LPD) is sufficient to programme altered growth and cardiovascular dysfunction in offspring. Here, we use an in vitro model comprising preimplantation culture in medium depleted in insulin and branched-chain amino acids (BCAA), two proposed embryo programming inductive factors from Emb-LPD studies, to examine the consequences for blastocyst organisation and, after embryo transfer (ET), postnatal disease origin. Two-cell embryos were cultured to blastocyst stage in defined KSOM medium supplemented with four combinations of insulin and BCAA concentrations.

The Role of Maternal Nutrition During the Periconceptional Period and Its Effect on Offspring Phenotype.

The early preimplantation embryo has been rigorously studied for decades to understand inherent reproductive and developmental mechanisms driving its morphogenesis from before fertilisation through to and beyond implantation. Recent research has demonstrated that this short developmental window is also critical for the embryo's interaction with external, maternal factors, particularly nutritional status. Here, maternal dietary quality has been shown to alter the pattern of development in an enduring way that can influence health throughout the lifetime.

Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study.

Importance: Cancer is the second leading cause of death worldwide. Current estimates on the burden of cancer are needed for cancer control planning.

Objective: To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 32 cancers in 195 countries and territories from 1990 to 2015.

Regulation of ribosomal RNA expression across the lifespan is fine-tuned by maternal diet before implantation.

Cells and organisms respond to nutrient deprivation by decreasing global rates of transcription, translation and DNA replication. To what extent such changes can be reversed is largely unknown. We examined the effect of maternal dietary restriction on RNA synthesis in the offspring.

Maternal diabetes promotes mTORC1 downstream signalling in rabbit preimplantation embryos.

The mammalian target of rapamycin complex 1 (mTORC1) is known to be a central cellular nutrient sensor and master regulator of protein metabolism; therefore, it is indispensable for normal embryonic development. We showed previously in a diabetic pregnancy that embryonic mTORC1 phosphorylation is increased in case of maternal hyperglycaemia and hypoinsulinaemia. Further, the preimplantation embryo is exposed to increased L-leucine levels during a diabetic pregnancy.

Estimating distributions of health state severity for the global burden of disease study.

Background: Many major causes of disability in the Global Burden of Disease (GBD) study present with a range of severity, and for most causes finding population distributions of severity can be difficult due to issues of sparse data, inconsistent measurement, and need to account for comorbidities. We developed an indirect approach to obtain severity distributions empirically from survey data.

Methods: Individual-level data were used from three large population surveys from the US and Australia that included self-reported prevalence of major diseases and injuries as well as generic health status assessments using the 12-Item Short Form Health Survey (SF-12).

Data linkage errors in hospital administrative data when applying a pseudonymisation algorithm to paediatric intensive care records.

Objectives: Our aim was to estimate the rate of data linkage error in Hospital Episode Statistics (HES) by testing the HESID pseudoanonymisation algorithm against a reference standard, in a national registry of paediatric intensive care records.

Setting: The Paediatric Intensive Care Audit Network (PICANet) database, covering 33 paediatric intensive care units in England, Scotland and Wales.

Participants: Data from infants and young people aged 0-19 years admitted between 1 January 2004 and 21 February 2014.

Cell signalling during blastocyst morphogenesis.

Blastocyst morphogenesis is prepared for even before fertilisation. Information stored within parental gametes can influence both maternal and embryonic gene expression programmes after egg activation at fertilisation. A complex network of intrinsic, cell-cell mediated and extrinsic, embryo-environment signalling mechanisms operates throughout cleavage, compaction and cavitation.