title: High fat diet induced developmental defects in the mouse: oocyte meiotic aneuploidy and fetal growth retardation/brain defects.
abstract: BACKGROUND
  Maternal obesity is associated with poor outcomes across the reproductive spectrum including infertility, increased time to pregnancy, early pregnancy loss, fetal loss, congenital abnormalities and neonatal conditions. Furthermore, the proportion of reproductive-aged woman that are obese in the population is increasing sharply. From current studies it is not clear if the origin of the reproductive complications is attributable to problems that arise in the oocyte or the uterine environment.
  
  
  RESULTS
  We examined the developmental basis of the reproductive phenotypes in obese animals by employing a high fat diet mouse model of obesity. We analyzed very early embryonic and fetal phenotypes, which can be parsed into three abnormal developmental processes that occur in obese mothers. The first is oocyte meiotic aneuploidy that then leads to early embryonic loss. The second is an abnormal process distinct from meiotic aneuploidy that also leads to early embryonic loss. The third is fetal growth retardation and brain developmental abnormalities, which based on embryo transfer experiments are not due to the obese uterine environment but instead must be from a defect that arises prior to the blastocyst stage.
  
  
  CONCLUSIONS
  Our results suggest that reproductive complications in obese females are, at least in part, from oocyte maternal effects. This conclusion is consistent with IVF studies where the increased pregnancy failure rate in obese women returns to the normal rate if donor oocytes are used instead of autologous oocytes. We postulate that preconceptional weight gain adversely affects pregnancy outcomes and fetal development. In light of our findings, preconceptional counseling may be indicated as the preferable, earlier target for intervention in obese women desiring pregnancy and healthy outcomes.
authors.affiliation: Washington University School of Medicine, Department of Obstetrics and Gynecology, St. Louis, Missouri, United States of America.
authors.forename: Kerri M
authors.initials: KM
authors.lastname: Luzzo
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Scott H
authors.initials: SH
authors.lastname: Purcell
authors.forename: Maggie
authors.initials: M
authors.lastname: Chi
authors.forename: Patricia T
authors.initials: PT
authors.lastname: Jimenez
authors.forename: Natalia
authors.initials: N
authors.lastname: Grindler
authors.forename: Tim
authors.initials: T
authors.lastname: Schedl
authors.forename: Kelle H
authors.initials: KH
authors.lastname: Moley
mesh_terms: D000782:Aneuploidy; D000818:Animals; D001921:Brain / Q000002:abnormalities* / Q000196:embryology* / Q000473:pathology; D033481:Chromosomes, Mammalian / Q000378:metabolism; D054885:Cumulus Cells / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D059305:Diet, High-Fat / Q000009:adverse effects*; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000473:pathology; D005247:Feeding Behavior; D005260:Female; D047109:Fetal Development; D005317:Fetal Growth Retardation / Q000473:pathology*; D006801:Humans; D008540:Meiosis; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000473:pathology / Q000648:ultrastructure; D008954:Models, Biological; D009765:Obesity / Q000473:pathology; D009865:Oocytes / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009929:Organ Size; D010641:Phenotype; D010920:Placenta / Q000473:pathology; D011247:Pregnancy; D014599:Uterus / Q000473:pathology