PMID- 22291969 OWN - NLM STAT- MEDLINE DCOM- 20120604 LR - 20220331 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 7 IP - 1 DP - 2012 TI - Inhibition of histone deacetylase activity in human endometrial stromal cells promotes extracellular matrix remodelling and limits embryo invasion. PG - e30508 LID - 10.1371/journal.pone.0030508 [doi] LID - e30508 AB - Invasion of the trophoblast into the maternal decidua is regulated by both the trophoectoderm and the endometrial stroma, and entails the action of tissue remodeling enzymes. Trophoblast invasion requires the action of metalloproteinases (MMPs) to degrade extracellular matrix (ECM) proteins and in turn, decidual cells express tissue inhibitors of MMPs (TIMPs). The balance between these promoting and restraining factors is a key event for the successful outcome of pregnancy. Gene expression is post-transcriptionally regulated by histone deacetylases (HDACs) that unpacks condensed chromatin activating gene expression. In this study we analyze the effect of histone acetylation on the expression of tissue remodeling enzymes and activity of human endometrial stromal cells (hESCs) related to trophoblast invasion control. Treatment of hESCs with the HDAC inhibitor trichostatin A (TSA) increased the expression of TIMP-1 and TIMP-3 while decreased MMP-2, MMP-9 and uPA and have an inhibitory effect on trophoblast invasion. Moreover, histone acetylation is detected at the promoters of TIMP-1 and TIMP-3 genes in TSA-treated. In addition, in an in vitro decidualized hESCs model, the increase of TIMP-1 and TIMP-3 expression is associated with histone acetylation at the promoters of these genes. Our results demonstrate that histone acetylation disrupt the balance of ECM modulators provoking a restrain of trophoblast invasion. These findings are important as an epigenetic mechanism that can be used to control trophoblast invasion. FAU - Estella, Carlos AU - Estella C AD - Fundacion Instituto Valenciano de Infertilidad, Valencia University, and Instituto Universitario IVI/INCLIVA, Valencia, Spain. FAU - Herrer, Isabel AU - Herrer I FAU - Atkinson, Stuart P AU - Atkinson SP FAU - Quinonero, Alicia AU - Quinonero A FAU - Martinez, Sebastian AU - Martinez S FAU - Pellicer, Antonio AU - Pellicer A FAU - Simon, Carlos AU - Simon C LA - eng PT - Evaluation Study PT - Journal Article DEP - 20120126 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Histone Deacetylase Inhibitors) RN - 0 (Hydroxamic Acids) RN - 0 (TIMP1 protein, human) RN - 0 (TIMP3 protein, human) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 0 (Tissue Inhibitor of Metalloproteinase-3) RN - 3X2S926L3Z (trichostatin A) RN - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator) RN - EC 3.4.24.24 (MMP2 protein, human) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Adult MH - Cells, Cultured MH - Down-Regulation/drug effects/genetics MH - Embryo Implantation/*drug effects/genetics/physiology MH - Endometrium/*drug effects/enzymology/metabolism MH - Extracellular Matrix/*drug effects/metabolism MH - Female MH - Gene Expression Regulation, Enzymologic/drug effects MH - Histone Deacetylase Inhibitors/*pharmacology MH - Humans MH - Hydroxamic Acids/pharmacology MH - Matrix Metalloproteinase 2/genetics/metabolism MH - Matrix Metalloproteinase 9/genetics/metabolism MH - Pregnancy MH - Stromal Cells/*drug effects/enzymology/metabolism MH - Tissue Inhibitor of Metalloproteinase-1/genetics/metabolism MH - Tissue Inhibitor of Metalloproteinase-3/genetics/metabolism MH - Urokinase-Type Plasminogen Activator/genetics/metabolism MH - Young Adult PMC - PMC3266920 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2012/02/01 06:00 MHDA- 2012/06/05 06:00 PMCR- 2012/01/26 CRDT- 2012/02/01 06:00 PHST- 2011/11/03 00:00 [received] PHST- 2011/12/22 00:00 [accepted] PHST- 2012/02/01 06:00 [entrez] PHST- 2012/02/01 06:00 [pubmed] PHST- 2012/06/05 06:00 [medline] PHST- 2012/01/26 00:00 [pmc-release] AID - PONE-D-11-22064 [pii] AID - 10.1371/journal.pone.0030508 [doi] PST - ppublish SO - PLoS One. 2012;7(1):e30508. doi: 10.1371/journal.pone.0030508. Epub 2012 Jan 26.