title: Decreased ovarian reserve, dysregulation of mitochondrial biogenesis, and increased lipid peroxidation in female mouse offspring exposed to an obesogenic maternal diet.
abstract: Maternal diet during pregnancy influences the later life reproductive potential of female offspring. We investigate the molecular mechanisms underlying the depletion of ovarian follicular reserve in young adult females following exposure to obesogenic diet in early life. Furthermore, we explore the interaction between adverse maternal diet and postweaning diet in generating reduced ovarian reserve. Female mice were exposed to either maternal obesogenic (high fat/high sugar) or maternal control dietin uteroand during lactation, then weaned onto either obesogenic or control diet. At 12 wk of age, the offspring ovarian reserve was depleted following exposure to maternal obesogenic diet (P< 0.05), but not postweaning obesogenic diet. Maternal obesogenic diet was associated with increased mitochondrial DNA biogenesis (copy numberP< 0.05; transcription factor A, mitochondrial expressionP< 0.05), increased mitochondrial antioxidant defenses [manganese superoxide dismutase (MnSOD)P< 0.05; copper/zinc superoxide dismutaseP< 0.05; glutathione peroxidase 4P< 0.01] and increased lipoxygenase expression (arachidonate 12-lipoxygenaseP< 0.05; arachidonate 15-lipoxygenaseP< 0.05) in the ovary. There was also significantly increased expression of the transcriptional regulator NF-κB (P< 0.05). There was no effect of postweaning diet on any measured ovarian parameters. Maternal diet thus plays a central role in determining follicular reserve in adult female offspring. Our observations suggest that lipid peroxidation and mitochondrial biogenesis are the key intracellular pathways involved in programming of ovarian reserve.-Aiken, C. E., Tarry-Adkins, J. L., Penfold, N. C., Dearden, L., Ozanne, S. E. Decreased ovarian reserve, dysregulation of mitochondrial biogenesis, and increased lipid peroxidation in female mouse offspring exposed to an obesogenic maternal diet.
authors.affiliation: *University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital and National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre, Cambridge, United Kingdom cema2@cam.ac.uk.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Aiken
authors.affiliation: *University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital and National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre, Cambridge, United Kingdom.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Tarry-Adkins
authors.affiliation: *University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital and National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre, Cambridge, United Kingdom.
authors.forename: Naomi C
authors.initials: NC
authors.lastname: Penfold
authors.affiliation: *University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital and National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre, Cambridge, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Dearden
authors.affiliation: *University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital and National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre, Cambridge, United Kingdom.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ozanne
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015227:Lipid Peroxidation / Q000235:genetics / Q000502:physiology*; D039382:Maternal Nutritional Physiological Phenomena / Q000235:genetics / Q000502:physiology; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009929:Organ Size; D065851:Ovarian Reserve / Q000235:genetics / Q000502:physiology*; D010053:Ovary / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
keywords: developmental programming; lipoxygenase; primordial follicle; reproductive potential