Ascorbic acid and CoQ10 ameliorate the reproductive ability of superoxide dismutase 1-deficient female mice†
Ascorbic acid and CoQ10 ameliorate the reproductive ability of superoxide dismutase 1-deficient female mice†
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DOI：
10.1093/biolre/ioz149
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发表时间：
2019-08
影响因子：
3.6
通讯作者：
Naoki Ishii;T. Homma;Jaeyong Lee;Hikaru Mitsuhashi;Ken‐ichi Yamada;N. Kimura;Yorihiro Yamamoto;J. Fujii
中科院分区：
文献类型：
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作者：
Naoki Ishii;T. Homma;Jaeyong Lee;Hikaru Mitsuhashi;Ken‐ichi Yamada;N. Kimura;Yorihiro Yamamoto;J. Fujii
超氧化物歧化酶1通过降低细胞内超氧化物阴离子的水平来抑制氧化应激。卵巢功能障碍和/或性激素的异常产生被怀疑是超氧化物歧化酶1敲除小鼠不育的原因。我们报道了通过在断奶后的敲除小鼠的饮用水中添加抗坏血酸和/或辅酶Q10两种抗氧化剂来挽救雌性敲除小鼠不育的尝试，并对其生殖能力进行了调查。在第一次分娩时，与野生型小鼠相比，80%未经治疗的基因敲除小鼠的产仔数较小（平均2.8对7.3只），补充这些抗氧化剂未能改善产仔数。然而，在基因敲除小鼠的第二次分娩中，由于给予抗氧化剂，分娩率从18%增加到44-75%。虽然在妊娠7.5天时，野生型和基因敲除小鼠的血浆黄体酮水平基本相同，并且这些抗氧化剂的补充没有改变，但基因敲除小鼠在第一次分娩后卵巢中较小的黄体细胞的大小在基因敲除小鼠中得到了显着改善。此外，补充抗坏血酸还能改善子宫/胎盘血管生成受损的情况。因此，我们得出结论，抗坏血酸和/或辅酶Q10参与维持卵巢和子宫/胎盘的稳态，以抵抗妊娠期间增强的损伤，并且它们的使用可能在提高女性生育能力方面具有积极作用。结果表明，抗氧化剂支持分娩时抗氧化应激的受精能力。
Abstract Superoxide dismutase 1 suppresses oxidative stress within cells by decreasing the levels of superoxide anions. A dysfunction of the ovary and/or an aberrant production of sex hormones are suspected causes for infertility in superoxide dismutase 1-knockout mice. We report on attempts to rescue the infertility in female knockout mice by providing two antioxidants, ascorbic acid and/or coenzyme Q10, as supplements in the drinking water of the knockout mice after weaning and on an investigation of their reproductive ability. On the first parturition, 80% of the untreated knockout mice produced smaller litter sizes compared with wild-type mice (average 2.8 vs 7.3 pups/mouse), and supplementing with these antioxidants failed to improve these litter sizes. However, in the second parturition of the knockout mice, the parturition rate was increased from 18% to 44–75% as the result of the administration of antioxidants. While plasma levels of progesterone at 7.5 days of pregnancy were essentially the same between the wild-type and knockout mice and were not changed by the supplementation of these antioxidants, sizes of corpus luteum cells, which were smaller in the knockout mouse ovaries after the first parturition, were significantly ameliorated in the knockout mouse with the administration of the antioxidants. Moreover, the impaired vasculogenesis in uterus/placenta was also improved by ascorbic acid supplementation. We thus conclude that ascorbic acid and/or coenzyme Q10 are involved in maintaining ovarian and uterus/placenta homeostasis against insults that are augmented during pregnancy and that their use might have positive effects in terms of improving female fertility. Summary sentence The results suggest that antioxidants support fertilizing ability against oxidative stress during parturition.