High Fat Diet Induced Developmental Defects in the Mouse: Oocyte Meiotic Aneuploidy and Fetal Growth Retardation/Brain Defects

Kerri M. Luzzo, Qiang Wang, Scott H. Purcell, Maggie Chi, Patricia T. Jimenez, Natalia Grindler, Tim Schedl, Kelle H. Moley

Research output: Contribution to journalArticle

148 Citations (Scopus)

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. Methodology/Principal Findings: 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/Significance: 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.

Original languageEnglish (US)
Article numbere49217
JournalPLoS One
Volume7
Issue number11
DOIs
StatePublished - Nov 12 2012

Fingerprint

Fetal Growth Retardation
aneuploidy
fetal development
High Fat Diet
Aneuploidy
high fat diet
Nutrition
growth retardation
Oocytes
Brain
oocytes
Fats
brain
Defects
pregnancy
mice
embryonic mortality
Pregnancy Outcome
obesity
Obesity

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Luzzo, K. M., Wang, Q., Purcell, S. H., Chi, M., Jimenez, P. T., Grindler, N., ... Moley, K. H. (2012). High Fat Diet Induced Developmental Defects in the Mouse: Oocyte Meiotic Aneuploidy and Fetal Growth Retardation/Brain Defects. PLoS One, 7(11), [e49217]. https://doi.org/10.1371/journal.pone.0049217

High Fat Diet Induced Developmental Defects in the Mouse : Oocyte Meiotic Aneuploidy and Fetal Growth Retardation/Brain Defects. / Luzzo, Kerri M.; Wang, Qiang; Purcell, Scott H.; Chi, Maggie; Jimenez, Patricia T.; Grindler, Natalia; Schedl, Tim; Moley, Kelle H.

In: PLoS One, Vol. 7, No. 11, e49217, 12.11.2012.

Research output: Contribution to journalArticle

Luzzo, KM, Wang, Q, Purcell, SH, Chi, M, Jimenez, PT, Grindler, N, Schedl, T & Moley, KH 2012, 'High Fat Diet Induced Developmental Defects in the Mouse: Oocyte Meiotic Aneuploidy and Fetal Growth Retardation/Brain Defects', PLoS One, vol. 7, no. 11, e49217. https://doi.org/10.1371/journal.pone.0049217
Luzzo, Kerri M. ; Wang, Qiang ; Purcell, Scott H. ; Chi, Maggie ; Jimenez, Patricia T. ; Grindler, Natalia ; Schedl, Tim ; Moley, Kelle H. / High Fat Diet Induced Developmental Defects in the Mouse : Oocyte Meiotic Aneuploidy and Fetal Growth Retardation/Brain Defects. In: PLoS One. 2012 ; Vol. 7, No. 11.
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