Decreased ovarian reserve, dysregulation of mitochondrial biogenesis, and increased lipid peroxidation in female mouse offspring exposed to an obesogenic maternal diet.
Decreased ovarian reserve, dysregulation of mitochondrial biogenesis, and increased lipid peroxidation in female mouse offspring exposed to an obesogenic maternal diet.
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DOI：
10.1096/fj.15-280800
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发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Ozanne SE
中科院分区：
文献类型：
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作者：
Aiken CE;Tarry-Adkins JL;Penfold NC;Dearden L;Ozanne SE
母亲怀孕期间的饮食会影响女性后代以后的生殖潜力。我们研究了年轻成年女性在早期暴露于致肥性饮食后卵巢卵泡储备耗竭的分子机制。此外，我们探讨了不良的母亲饮食和断奶后饮食在产生卵巢储备减少中的相互作用。雌性小鼠在子宫内和哺乳期暴露于母体致肥性（高脂肪/高糖）或母体对照饮食中，然后断奶后食用致肥性或对照饮食。在12周龄时，暴露于母体致肥饲料的子代卵巢储备被耗尽（P < 0.05），但在断奶后的致肥饲料中没有出现这种情况。母体致肥饮食增加了线粒体DNA生物发生（拷贝数P < 0.05，转录因子A、线粒体表达P < 0.05），增加了线粒体抗氧化防御能力[锰超氧化物歧化酶（MnSOD）] P < 0.05；铜锌超氧化物歧化酶P < 0.05；谷胱甘肽过氧化物酶4 P < 0.01]和脂肪加氧酶（花生四烯酸12-脂肪加氧酶P < 0.05；花生四烯酸15-脂肪加氧酶P < 0.05）表达升高。转录调节因子NF-κB的表达也显著升高（P < 0.05）。断奶后饮食对任何测量的卵巢参数都没有影响。因此，母亲的饮食在决定成年雌性后代的卵泡储备中起着核心作用。我们的观察表明，脂质过氧化和线粒体生物发生是参与卵巢储备程序的关键细胞内途径。-Aiken， C. E, Tarry-Adkins， J. L, Penfold, n.c., Dearden， L., Ozanne， S. E.暴露于致肥性母性饮食的雌性小鼠后代卵巢储备减少，线粒体生物发生失调，脂质过氧化增加。
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 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 12-lipoxygenase P < 0.05; arachidonate 15-lipoxygenase P < 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.