TY - JOUR
T1 - Ascorbic acid and CoQ10 ameliorate the reproductive ability of superoxide dismutase 1-deficient female mice
AU - Ishii, Naoki
AU - Homma, Takujiro
AU - Lee, Jaeyong
AU - Mitsuhashi, Hikaru
AU - Yamada, Ken Ichi
AU - Kimura, Naoko
AU - Yamamoto, Yorihiro
AU - Fujii, And Junichi
N1 - Funding Information:
∗Correspondence: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan. Tel: +81-23-628-5227; Fax: +81-23-628-5230; E-mail: jfujii@med.id.yamagata-u.ac.jp †Grant Support: This work was supported by JSPS KAKENHI Grant-in-Aid for Scientific Research (C) (15 K08294) to JF and, in part, by the YU-COE Program [M31–3] to TH, NK, and JF from Yamagata University.
Funding Information:
This work was supported by JSPS KAKENHI Grant-in-Aid for Scientific Research (C) (15 K08294) to JF and, in part, by the YU-COE Program [M31 3] to TH, NK, and JF from Yamagata University.
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved.
PY - 2020/2/12
Y1 - 2020/2/12
N2 - 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.
AB - 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.
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U2 - 10.1093/biolre/ioz149
DO - 10.1093/biolre/ioz149
M3 - Article
C2 - 31373359
AN - SCOPUS:85079323622
VL - 102
SP - 102
EP - 115
JO - Biology of Reproduction
JF - Biology of Reproduction
SN - 0006-3363
IS - 1
ER -