title: 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.
authors.affiliation: Dpto, de Reproducción Animal, INIA, Avda Puerta de Hierro no, 12, Local 10, Madrid 28040, Spain. a.mirandabedate@uu.nl.
authors.forename: Alberto
authors.initials: A
authors.lastname: Miranda
authors.forename: Angela P
authors.initials: AP
authors.lastname: López-Cardona
authors.forename: Ricardo
authors.initials: R
authors.lastname: Laguna-Barraza
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calle
authors.forename: Irene
authors.initials: I
authors.lastname: López-Vidriero
authors.forename: Belén
authors.initials: B
authors.lastname: Pintado
authors.forename: Alfonso
authors.initials: A
authors.lastname: Gutiérrez-Adán
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight; D001827:Body Height; D059305:Diet, High-Fat; D005260:Female; D020567:Fetal Weight; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D007230:Infant, Low Birth Weight / Q000254:growth & development; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D010641:Phenotype; D012727:Sex Characteristics