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Transcriptome profiling of liver of non-genetic low birth weight and long term health consequences.

ABSTRACT: BACKGROUND: It is believed that the main factors of low prenatal growth in mammals are genetic and environmental. We used isogenic mice maintained in standard conditions to analyze how natural non-genetic microsomia (low birth weight) is produced in inbred mice and its long term effect on health. To better understand the molecular basis of non-genetic microsomia, we undertook transcriptome profiling of both male and female livers from small and normal size mice at birth. RESULTS: Naturally occurring neonatal microsomia was defined as a gender-specific weanling weight under the 10th percentile of the colony. Birth weight variation was similar in inbred and outbred lines. Mice were phenotyped by weight, size, blood pressure, organ size, their response to a glucose challenge, and survival rates. Regardless of diet, adult mice born with microsomia showed a significantly lower body weight and size, and differences in the weight of several organs of microsomic adult mice compared to normal birth weight adults were found. After a high-fat diet, microsomic mice were less prone to obesity, showing a better glucose tolerance and lower blood pressure. Through a transcriptome analysis, we detected a different pattern of mRNA transcription in the liver at birth comparing male vs female and microsomic vs normal mice, noting some modifications in epigenetic regulatory genes in females and modifications in some growth factor genes in males. Finally, using embryo transfer of embryos of different quality and age, we identified a putative preimplantation origin of this non-genetic microsomia. CONCLUSIONS: (1) neonatal microsomia is not always a risk factor for adult metabolic syndrome, (2) neonatal non-genetic microsomia displays changes in the expression of important epigenetic genes and changes in liver mRNA transcription profile at birth, exaggerating sexual dimorphism, and (3) random preimplantation phenotypic variability could partially explain body birth weight variation in isogenic lines.

SUBMITTER: Miranda A

PROVIDER: S-EPMC4229907 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Transcriptome profiling of liver of non-genetic low birth weight and long term health consequences.

Miranda Alberto A López-Cardona Angela P AP Laguna-Barraza Ricardo R Calle Alexandra A López-Vidriero Irene I Pintado Belén B Gutiérrez-Adán Alfonso A

BMC genomics 20140501

<h4>Background</h4>It is believed that the main factors of low prenatal growth in mammals are genetic and environmental. We used isogenic mice maintained in standard conditions to analyze how natural non-genetic microsomia (low birth weight) is produced in inbred mice and its long term effect on health. To better understand the molecular basis of non-genetic microsomia, we undertook transcriptome profiling of both male and female livers from small and normal size mice at birth.<h4>Results</h4>Na ...[more]

PMID: 24884990

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Project description:BackgroundLow birth weight (LBW) is one of the leading causes of adverse perinatal outcomes and is closely related to neonatal disease and death. The incidence of LBW has been increasing. The aim of this study was to investigate the current incidence rate and factors affecting low birth weight infants and perinatal outcomes of full-term low birth weight infants in mainland China.MethodsThis paper describes a retrospective analysis of children born in 39 hospitals of different types in 14 different provinces, municipalities, and autonomous regions in seven districts within China throughout 2011. The data were first collected in hardcopy format and then entered into computer network databases. Data covering a total of 112,441 cases were collected. Cases were excluded if data were incomplete and in the case of miscarriage before 24 weeks of gestation, multiple pregnancies, or induction of labor due to fetal malformation, intrauterine death, and other reasons, leaving a total of 101,163 cases. SPSS 18.0 and SAS 9.2 statistical packages were used to analyze the collected data.ResultsAccording to this research, the incidence of LBW in mainland China was 6.1%, which is higher than the 5.87% reported in 2000, and it varied across different areas. The incidence of LBW was significantly higher in tertiary care hospitals than in secondary care hospitals. LBW was found to be associated with maternal age of less than 20 years, low level of maternal education, previous histories of adverse pregnancies, and with pregnancy comorbidities and complications, such as hypertensive disorders during pregnancy, anemia, oligohydramnios, premature rupture of membranes, and gestational diabetes. The rates of stillbirths, severe neonatal asphyxia, and deaths among full-term LBW infants were 2.42%, 0.83%, and 3.49%, respectively. The rates of stillbirths and neonatal deaths among full-term LBW infants born by caesarean section were 0.5% and 1.0%, respectively, which was lower than vaginal delivery.ConclusionsThe incidence of LBW has increased in China. LBW is a leading cause of adverse pregnancy outcomes. Health care during pregnancy and management of high-risk factors for LBW may reduce the incidence of LWB and the death rate of LBW infants.

Project description:Infants born prematurely, particularly extremely low birth weight infants (ELBW) have altered gut microbial communities. Factors such as maternal health, gut immaturity, delivery mode, and antibiotic treatments are associated with microbiota disturbances, and are linked to an increased risk of certain diseases such as necrotising enterocolitis. Therefore, there is a requirement to optimally characterise microbial profiles in this at-risk cohort, via standardisation of methods, particularly for studying the influence of microbiota therapies (e.g. probiotic supplementation) on community profiles and health outcomes. Profiling of faecal samples using the 16S rRNA gene is a cost-efficient method for large-scale clinical studies to gain insights into the gut microbiota and additionally allows characterisation of cohorts were sample quantities are compromised (e.g. ELBW infants). However, DNA extraction method, and the 16S rRNA region targeted can significantly change bacterial community profiles obtained, and so confound comparisons between studies. Thus, we sought to optimise a 16S rRNA profiling protocol to allow standardisation for studying ELBW infant faecal samples, with or without probiotic supplementation.Using ELBW faecal samples, we compared three different DNA extraction methods, and subsequently PCR amplified and sequenced three hypervariable regions of the 16S rRNA gene (V1 + V2 + V3), (V4 + V5) and (V6 + V7 + V8), and compared two bioinformatics approaches to analyse results (OTU and paired end). Paired shotgun metagenomics was used as a 'gold-standard'.Results indicated a longer bead-beating step was required for optimal bacterial DNA extraction and that sequencing regions (V1 + V2 + V3) and (V6 + V7 + V8) provided the most representative taxonomic profiles, which was confirmed via shotgun analysis. Samples sequenced using the (V4 + V5) region were found to be underrepresented in specific taxa including Bifidobacterium, and had altered diversity profiles. Both bioinformatics 16S rRNA pipelines used in this study (OTU and paired end) presented similar taxonomic profiles at genus level.We determined that DNA extraction from ELBW faecal samples, particularly those infants receiving probiotic supplementation, should include a prolonged beat-beating step. Furthermore, use of the 16S rRNA (V1 + V2 + V3) and (V6 + V7 + V8) regions provides reliable representation of ELBW microbiota profiles, while inclusion of the (V4 + V5) region may not be appropriate for studies where Bifidobacterium constitutes a resident microbiota member.

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Transcriptome profiling of liver of non-genetic low birth weight and long term health consequences.

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Transcriptome profiling of liver of non-genetic low birth weight and long term health consequences.

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