Document Detail


Progesterone and DNA damage encourage uterine cell proliferation and decidualization through up-regulating ribonucleotide reductase 2 expression during early pregnancy in mice.
MedLine Citation:
PMID:  22403396     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Embryo implantation into the maternal uterus is a crucial step for the successful establishment of mammalian pregnancy. Following the attachment of embryo to the uterine luminal epithelium, uterine stromal cells undergo steroid hormone-dependent decidualization, which is characterized by stromal cell proliferation and differentiation. The mechanisms underlying steroid hormone-induced stromal cell proliferation and differentiation during decidualization are still poorly understood. Ribonucleotide reductase, consisting of two subunits (RRM1 and RRM2), is a rate-limiting enzyme in deoxynucleotide production for DNA synthesis and plays an important role in cell proliferation and tumorgenicity. Based on our microarray analysis, Rrm2 expression was significantly higher at implantation sites compared with interimplantation sites in mouse uterus. However, the expression, regulation, and function of RRM2 in mouse uterus during embryo implantation and decidualization are still unknown. Here we show that although both RRM1 and RRM2 expression are markedly induced in mouse uterine stromal cells undergoing decidualization, only RRM2 is regulated by progesterone, a key regulator of decidualization. Further studies showed that the induction of progesterone on RRM2 expression in stromal cells is mediated by the AKT/c-MYC pathway. RRM2 can also be induced by replication stress and DNA damage during decidualization through the ATR/ATM-CHK1-E2F1 pathway. The weight of implantation sites and deciduoma was effectively reduced by specific inhibitors for RRM2. The expression of decidual/trophoblast prolactin-related protein (Dtprp), a reliable marker for decidualization in mice, was significantly reduced in deciduoma and steroid-induced decidual cells after HU treatment. Therefore, RRM2 may be an important effector of progesterone signaling to induce cell proliferation and decidualization in mouse uterus.
Authors:
Wei Lei; Xu-Hui Feng; Wen-Bo Deng; Hua Ni; Zhi-Rong Zhang; Bo Jia; Xin-Ling Yang; Tong-Song Wang; Ji-Long Liu; Ren-Wei Su; Xiao-Huan Liang; Qian-Rong Qi; Zeng-Ming Yang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-08
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-07     Completed Date:  2012-07-30     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  15174-92     Citation Subset:  IM    
Affiliation:
Department of Biology, Shantou University, Shantou 515063, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Cell Proliferation / drug effects*
Cells, Cultured
DNA Damage*
Decidua / cytology,  drug effects,  metabolism
E2F1 Transcription Factor / genetics,  metabolism
Embryo Implantation / drug effects,  genetics
Female
Gene Expression Regulation, Developmental / drug effects
Hydroxyurea / pharmacology
Male
Mice
Ovariectomy
Pregnancy
Progesterone / pharmacology*
Protein Binding
Proto-Oncogene Proteins c-myc / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Ribonucleoside Diphosphate Reductase / genetics*,  metabolism
Ribonucleotide Reductases / genetics,  metabolism
Signal Transduction / drug effects
Stromal Cells / drug effects,  metabolism
Time Factors
Uterus / cytology,  drug effects*,  metabolism
Chemical
Reg. No./Substance:
0/E2F1 Transcription Factor; 0/E2f1 protein, mouse; 0/Myc protein, mouse; 0/Proto-Oncogene Proteins c-myc; 127-07-1/Hydroxyurea; 57-83-0/Progesterone; EC 1.17.4.-/Ribonucleotide Reductases; EC 1.17.4.-/ribonucleotide reductase M2; EC 1.17.4.1/Ribonucleoside Diphosphate Reductase; EC 1.17.4.1/Rrm1 protein, mouse
Comments/Corrections

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


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