Decreased ovarian reserve, dysregulation of mitochondrial biogenesis, and increased lipid peroxidation in female mouse offspring exposed to an obesogenic maternal diet

被引:60
作者
Aiken, Catherine E. [1 ,2 ,3 ,4 ]
Tarry-Adkins, Jane L. [1 ,2 ]
Penfold, Naomi C. [1 ,2 ]
Dearden, Laura [1 ,2 ]
Ozanne, Susan E. [1 ,2 ]
机构
[1] Univ Cambridge, Metab Res Labs, Level 4,Box 289,Hills Rd, Cambridge CB2 OQQ, England
[2] Addenbrookes Hosp, MRC Metab Dis Unit, Inst Metab Sci, Cambridge, England
[3] Univ Cambridge, Dept Obstet & Gynaecol, Rosie Hosp, Cambridge, England
[4] Cambridge Comprehens Biomed Res Ctr, Natl Inst Hlth Res, Cambridge, England
基金
英国惠康基金;
关键词
developmental programming; reproductive potential; primordial follicle; lipoxygenase; NF-KAPPA-B; X-LINKED INHIBITOR; HIGH-FAT-DIET; NATURAL MENOPAUSE; DNA-DAMAGE; OBESITY; EXPRESSION; NUTRITION; PREGNANCY; APOPTOSIS;
D O I
10.1096/fj.15-280800
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 post-weaning diet in generating reduced ovarian reserve. Female mice were exposed to either maternal obesogenic (high fat/high sugar) or maternal control diet in utero and 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 number P < 0.05; transcription factor A, mitochondrial expression P < 0.05), increased mitochondrial antioxidant defenses [manganese superoxide dismutase (MnSOD) P < 0.05; copper/zinc superoxide dismutase P < 0.05; glutathione peroxidase 4 P < 0.01] and increased lipoxygenase expression (arachidonate 12lipoxygenaseP< 0.05; arachidonate 15-lipoxygenase P < 0.05) in the ovary. There was also significantly increased expression of the transcriptional regulator NF-kappa B (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. FASEB J. 30, 1548-1556 (2016). www.fasebj.org
引用
收藏
页码:1548 / 1556
页数:9
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