Document Detail

Cystathionine beta-synthase is essential for female reproductive function.
MedLine Citation:
PMID:  16984962     Owner:  NLM     Status:  MEDLINE    
In human reproduction, hyperhomocysteinemia has been reported as a risk factor for early pregnancy loss and congenital birth defects. Hyperhomocysteinemia is also recognized as a cause of maternal obstetric complications such as preeclampsia. The role of plasma hyperhomocysteinemia in female fertility was examined using cystathionine beta synthase knockout (cbs KO) mice. Cbs KO females were infertile, showed alterations in the estrus cycle and an increased progesterone response during pseudo-pregnancy induction. Both cbs KO ovaries and ovulated oocytes showed no major morphological alterations. However, placental and uterine masses were decreased at day 18 of pregnancy and showed morphological abnormalities. In cbs-KO pregnant females, the number of uterine implantation sites was not decreased despite the low number of surviving embryos. Fertility was restored when cbs-deficient ovaries were transplanted to normal ovarectomized recipients. We detected an increased uterine expression of Grp78, a marker of endoplasmic reticulum stress, which was accompanied by the decreased levels of uterine cbs mRNA in both hyperhomocysteinemic heterozygous (fertile) and homozygous (non-fertile) females. Our results indicate that cbs -/- female infertility is a consequence of the uterine failure and demonstrate that uterine endoplasmic reticulum stress and cbs expression are not determinant of infertility, suggesting that uterine dysfunction is a consequence of either hyperhomocysteinemia or other factor(s) in the uterine environment of cbs -/- animals. In summary, these studies demonstrate the potential importance of homocysteine levels for uterine handling of embryos.
Mario A Guzmán; María A Navarro; Ricardo Carnicer; Alfonso J Sarría; Sergio Acín; Carmen Arnal; Pedro Muniesa; Joaquín C Surra; José M Arbonés-Mainar; Nobuyo Maeda; Jesús Osada
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-09-19
Journal Detail:
Title:  Human molecular genetics     Volume:  15     ISSN:  0964-6906     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-10-17     Completed Date:  2006-12-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  3168-76     Citation Subset:  IM    
Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Miguel Servet 177, E-50013 Zaragoza, Spain.
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MeSH Terms
Cystathionine beta-Synthase / genetics*,  physiology
Endoplasmic Reticulum / chemistry,  metabolism
Estrous Cycle
Heat-Shock Proteins / analysis
Hyperhomocysteinemia / genetics,  physiopathology*
Infertility, Female / enzymology,  genetics*,  physiopathology
Mice, Inbred C57BL
Mice, Knockout
Molecular Chaperones / analysis
Uterus / cytology,  physiopathology*
Reg. No./Substance:
0/Heat-Shock Proteins; 0/Molecular Chaperones; 0/molecular chaperone GRP78; EC beta-Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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