Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortion
Historical data in the 1950s suggests that 7%, 11%, 33%, and 87% of couples were infertile by ages 30, 35, 40 and 45, respectively. Up to 22.3% of infertile couples have unexplained infertility. Oxidative stress is associated with male and female infertility. However, there is insufficient evidence...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-01-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231714000664 |
| _version_ | 1811248417003798528 |
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| author | Takamasa Ishii Masaki Miyazawa Yumi Takanashi Maya Tanigawa Kayo Yasuda Hiromi Onouchi Noboru Kawabe Junji Mitsushita Phil S. Hartman Naoaki Ishii |
| author_facet | Takamasa Ishii Masaki Miyazawa Yumi Takanashi Maya Tanigawa Kayo Yasuda Hiromi Onouchi Noboru Kawabe Junji Mitsushita Phil S. Hartman Naoaki Ishii |
| author_sort | Takamasa Ishii |
| collection | DOAJ |
| description | Historical data in the 1950s suggests that 7%, 11%, 33%, and 87% of couples were infertile by ages 30, 35, 40 and 45, respectively. Up to 22.3% of infertile couples have unexplained infertility. Oxidative stress is associated with male and female infertility. However, there is insufficient evidence relating to the influence of oxidative stress on the maintenance of a viable pregnancy, including pregnancy complications and fetal development. Recently, we have established Tet-mev-1 conditional transgenic mice, which can express the doxycycline-induced mutant SDHCV69E transgene and experience mitochondrial respiratory chain dysfunction leading to intracellular oxidative stress. In this report, we demonstrate that this kind of abnormal mitochondrial respiratory chain-induced chronic oxidative stress affects fertility, pregnancy and delivery rates as well as causes recurrent abortions, occasionally resulting in maternal death. Despite this, spermatogenesis and early embryogenesis are completely normal, indicating the mutation's effects to be rather subtle. Female Tet-mev-1 mice exhibit thrombocytosis and splenomegaly in both non-pregnant and pregnant mice as well as placental angiodysplasia with reduced Flt-1 protein leading to hypoxic conditions, which could contribute to placental inflammation and fetal abnormal angiogenesis. Collectively these data strongly suggest that chronic oxidative stress caused by mitochondrial mutations provokes spontaneous abortions and recurrent miscarriage resulting in age-related female infertility. |
| first_indexed | 2024-04-12T15:27:43Z |
| format | Article |
| id | doaj.art-086130bfc5bc432ea41d512314232602 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-12T15:27:43Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-086130bfc5bc432ea41d5123142326022022-12-22T03:27:12ZengElsevierRedox Biology2213-23172014-01-012C67968510.1016/j.redox.2014.05.001Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortionTakamasa Ishii0Masaki Miyazawa1Yumi Takanashi2Maya Tanigawa3Kayo Yasuda4Hiromi Onouchi5Noboru Kawabe6Junji Mitsushita7Phil S. Hartman8Naoaki Ishii9Department of Molecular Life Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, JapanDepartment of Molecular Life Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, JapanDepartment of Molecular Life Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, JapanDepartment of Molecular Life Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, JapanDepartment of Molecular Life Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, JapanDepartment of Ophthalmology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, JapanEducation and Research Support Center, Tokai University, 143 Shimokasuya, Isehara, Kanagawa 259-1193, JapanDepartment of Obstetrics and Gynecology, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya, Saitama 330-8503, JapanDepartment of Biology, Texas Christian University, Fort Worth, TX 76129, USADepartment of Molecular Life Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, JapanHistorical data in the 1950s suggests that 7%, 11%, 33%, and 87% of couples were infertile by ages 30, 35, 40 and 45, respectively. Up to 22.3% of infertile couples have unexplained infertility. Oxidative stress is associated with male and female infertility. However, there is insufficient evidence relating to the influence of oxidative stress on the maintenance of a viable pregnancy, including pregnancy complications and fetal development. Recently, we have established Tet-mev-1 conditional transgenic mice, which can express the doxycycline-induced mutant SDHCV69E transgene and experience mitochondrial respiratory chain dysfunction leading to intracellular oxidative stress. In this report, we demonstrate that this kind of abnormal mitochondrial respiratory chain-induced chronic oxidative stress affects fertility, pregnancy and delivery rates as well as causes recurrent abortions, occasionally resulting in maternal death. Despite this, spermatogenesis and early embryogenesis are completely normal, indicating the mutation's effects to be rather subtle. Female Tet-mev-1 mice exhibit thrombocytosis and splenomegaly in both non-pregnant and pregnant mice as well as placental angiodysplasia with reduced Flt-1 protein leading to hypoxic conditions, which could contribute to placental inflammation and fetal abnormal angiogenesis. Collectively these data strongly suggest that chronic oxidative stress caused by mitochondrial mutations provokes spontaneous abortions and recurrent miscarriage resulting in age-related female infertility.http://www.sciencedirect.com/science/article/pii/S2213231714000664MitochondriaSDHCInfertilityAbortionOxidative stress |
| spellingShingle | Takamasa Ishii Masaki Miyazawa Yumi Takanashi Maya Tanigawa Kayo Yasuda Hiromi Onouchi Noboru Kawabe Junji Mitsushita Phil S. Hartman Naoaki Ishii Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortion Redox Biology Mitochondria SDHC Infertility Abortion Oxidative stress |
| title | Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortion |
| title_full | Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortion |
| title_fullStr | Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortion |
| title_full_unstemmed | Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortion |
| title_short | Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortion |
| title_sort | genetically induced oxidative stress in mice causes thrombocytosis splenomegaly and placental angiodysplasia that leads to recurrent abortion |
| topic | Mitochondria SDHC Infertility Abortion Oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S2213231714000664 |
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