Document Detail


Involvement of 20alpha-hydroxysteroid dehydrogenase in the maintenance of pregnancy in mice.
MedLine Citation:
PMID:  18667791     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The enzyme 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) catabolizes progesterone into a biologically inactive steroid, 20alpha-dihydroprogesterone (20alpha-OHP). In the corpora lutea of rats and mice, 20alpha-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 20alpha-HSD in the maintenance of pregnancy using mice with targeted disruption of the 20alpha-HSD gene. We first confirmed that the number of pups was significantly smaller in 20alpha-HSD-/- pairs than in 20alpha-HSD+/+ pairs. We then mated 20alpha-HSD+/- males and females so that each pregnant female produced 20alpha-HSD+/+, 20alpha-HSD+/- and 20alpha-HSD-/- offspring. The genotype ratio of the offspring did not match the Mendel's law of inheritance, and the numbers of 20alpha-HSD+/- and 20alpha-HSD-/- offspring were smaller than expected values. Although the genotype ratio of fetuses on days 13, 15 and 18 of pregnancy matched the Mendel's 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 20alpha-HSD+/+ embryos to 20alpha-HSD+/+ or 20alpha-HSD-/- females and found that the number of offspring was significantly smaller in 20alpha-HSD-/- dams than in 20alpha-HSD+/+ dams. Expression of 20alpha-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 20alpha-HSD-/- fetuses than in the 20alpha-HSD+/+ fetuses, while those of 20alpha-OHP were lower in the 20alpha-HSD-/- fetuses than in the 20alpha-HSD+/+ fetuses. These results suggest that both maternal and fetal 20alpha-HSD play a role in maintaining normal pregnancy at least partially by reducing progesterone concentrations in fetuses.
Authors:
Jae-hyek Choi; Maho Ishida; Takashi Matsuwaki; Keitaro Yamanouchi; Masugi Nishihara
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-30
Journal Detail:
Title:  The Journal of reproduction and development     Volume:  54     ISSN:  0916-8818     ISO Abbreviation:  J. Reprod. Dev.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2009-01-08     Completed Date:  2009-02-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9438792     Medline TA:  J Reprod Dev     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  408-12     Citation Subset:  IM    
Affiliation:
Department of Veterinary Physiology, Veterinary Medical Science, The University of Tokyo, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
20-alpha-Dihydroprogesterone / analysis
20-alpha-Hydroxysteroid Dehydrogenase / deficiency,  genetics,  physiology*
Animals
Crosses, Genetic
Female
Fetal Weight
Fetus / chemistry,  enzymology
Gene Expression
Gestational Age
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Ovary / enzymology
Placenta / enzymology
Pregnancy
Pregnancy Maintenance / physiology*
Progesterone / analysis
RNA, Messenger / analysis
Uterus / enzymology
Chemical
Reg. No./Substance:
0/RNA, Messenger; 145-14-2/20-alpha-Dihydroprogesterone; 57-83-0/Progesterone; EC 1.1.1.149/20-alpha-Hydroxysteroid Dehydrogenase

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