Involvement of 20α-Hydroxysteroid Dehydrogenase in the Maintenance of Pregnancy in Mice
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概要
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The enzyme 20α-hydroxysteroid dehydrogenase (20α-HSD) catabolizes progesterone into a biologically inactive steroid, 20α-dihydroprogesterone (20α-OHP). In the corpora lutea of rats and mice, 20α-HSD is considered to be involved in functional luteolysis. It is also distributed in other tissues including the placenta, endometrial epithelia and fetal skin, although the roles it plays in these tissues remain to be elucidated. In the present study, we investigated the role of 20α-HSD in the maintenance of pregnancy using mice with targeted disruption of the 20α-HSD gene. We first confirmed that the number of pups was significantly smaller in 20α-HSD-/- pairs than in 20α-HSD+/+ pairs. We then mated 20α-HSD +/- males and females so that each pregnant female produced 20α-HSD+/+, 20α-HSD+/- and 20α-HSD-/- offspring. The genotype ratio of the offspring did not match the Mendels law of inheritance, and the numbers of 20α-HSD+/- and 20 α-HSD-/- offspring were smaller than expected values. Although the genotype ratio of fetuses on days 13, 15 and 18 of pregnancy matched the Mendels law, the total number of fetuses on day 18 was significantly smaller than that on day 13, suggesting that fetal loss occurred during late pregnancy. Next, we transferred 20α-HSD+/+ embryos to 20α-HSD+/+ or 20α-HSD -/- females and found that the number of offspring was significantly smaller in 20α-HSD-/- dams than in 20 α-HSD+/+ dams. Expression of 20α-HSD mRNA in the fetus, placenta and uterus progressively increased from day 11 to 18 of pregnancy. In addition, concentrations of progesterone were significantly higher in the 20α-HSD-/- fetuses than in the 20α-HSD+/+ fetuses, while those of 20α-OHP were lower in the 20α-HSD -/- fetuses than in the 20α-HSD+/+ fetuses. These results suggest that both maternal and fetal 20α-HSD play a role in maintaining normal pregnancy at least partially by reducing progesterone concentrations in fetuses.
- 2008-12-01
著者
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CHOI Jae-hyek
Department of Veterinary Physiology, Veterinary Medical Science, The University of Tokyo
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ISHIDA Maho
Department of Physiology, Interdisciplinary Graduate School of Medicine and Engineering, University
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MATSUWAKI Takashi
Department of Veterinary Physiology, Veterinary Medical Science, The University of Tokyo
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YAMANOUCHI Keitaro
Department of Veterinary Physiology, Veterinary Medical Science, The University of Tokyo
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NISHIHARA Masugi
Department of Veterinary Physiology, Veterinary Medical Science, The University of Tokyo
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Yamanouchi K
Waseda Univ. Saitama
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Matsuwaki Takashi
Dep. Of Veterinary Physiology Veterinary Medical Sci. The Univ. Of Tokyo
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Matsuwaki Takashi
Department Of Veterinary Physiology Veterinary Medical Science The University Of Tokyo
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Yamanouchi K
Department Of Veterinary Physiology Graduate School Of Agricultural And Life Sciences The University
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Yamanouchi Keitaro
Department Of Veterinary Physiology Veterinary Medical Science The University Of Tokyo
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Yamanouchi Keitaro
Department Of Veterinary Physiology Graduate School Of Agricultural And Life Sciences The University
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Choi Jae-hyek
Department Of Veterinary Physiology Veterinary Medical Science The University Of Tokyo
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Nishihara Masugi
Department Of Veterinary Physiology Graduate School Of Agricultural And Life Sciences The University
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Nishihara Masugi
Department Of Veterinary Physiology Veterinary Medical Science The University Of Tokyo
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Takahashi M
Department Of Veterinary Physiology Veterinary Medical Science The University Of Tokyo
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Ishida Maho
Department Of Physiology Interdisciplinary Graduate School Of Medicine And Engineering University Of
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Takahashi M
Ajinomoto Co. Tokyo Jpn
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Ishida Maho
Department Of Veterinary Physiology Veterinary Medical Science The University Of Tokyo
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Yokouchi Kou
Laboratory Of Applied Genetics Graduate School Of Agricultural And Life Sciences The University Of T
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Takahashi Michio
Res. Inst. For Health Fundamentals Ajinomoto Co. Inc.
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Nishihara Masugi
Department Of Veterinary Physiology The University Of Tokyo
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Nishihara Masugi
Department Of Veterinary Physiology Graduate School Of Agricultural And Life Sciences The University Of Tokyo
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Matsuwaki Takashi
Department Of Veterinary Physiology Graduate School Of Agricultural And Life Sciences The University Of Tokyo
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NISHIHARA MASUGI
Department of Physiology, Yokohama City University School of Medicine
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NISHIHARA Masugi
Department of Physiology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi
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