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Cystathionine β-synthase deficiency causes infertility by impairing decidualization and gene expression networks in uterus implantation sites.
MedLine Citation:
PMID:  22617046     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Hyperhomocysteinemia has been reported in human reproduction as a risk factor for early pregnancy loss, preeclampsia and congenital birth defects like spina bifida. Female infertility was also observed in cystathionine beta synthase deficient mice (Cbs-KO) as an animal model for severe hyperhomocysteinemia. The aim for the present research was to elucidate the time-point of pregnancy loss and to pinpoint gene and cellular changes involved in the underlying pathological mechanism. By mating 90-day-old wild-type and Cbs-KO female mice with their homologous male partners, we found that pregnancy loss in Cbs-KO occurred between the 8(th) and 12(th) gestation day during placenta formation. DNA microarrays were carried out on uterus from implantation and inter-implantation samples obtained on day 8(th). The results allowed us to select genes potentially involved in embryo death which were individually confirmed by RT-qPCR and their expressions were also followed throughout pregnancy. We found that changes in expression of Calb1, Ttr, Expi, Inmt, Spink3, Rpgrip1, Krt15, Mt-4, Gzmc, Gzmb, Tdo2 and Afp were important for pregnancy success, since a different regulation in Cbs-KO mice was found. Also, differences in relationships among selected genes were observed, indicating a dysregulation of these genes in Cbs-KO females. In conclusion, our data provide more information on the gene expression cascade and its timely regulated process required for a successful pregnancy. In addition, it unveils new potential avenues to explore further investigations in pregnancy loss.
Authors:
Mario Nuño-Ayala; Natalia Guillen; Carmen Arnal; Jose M Lou-Bonafonte; Alba de Martino; Jose-Antonio García-de-Jalón; Sonia Gascón; Lourdes Osaba; Jesus Osada; María-Angeles Navarro
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-22
Journal Detail:
Title:  Physiological genomics     Volume:  -     ISSN:  1531-2267     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815683     Medline TA:  Physiol Genomics     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
University of Zaragoza.
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