TY - JOUR
T1 - Transcription factor ETS1 is critical for human uterine decidualization
AU - Kessler, Cherie A.
AU - Schroeder, Jennifer K.
AU - Brar, Anoop K.
AU - Handwerger, Stuart
PY - 2006/2
Y1 - 2006/2
N2 - The aim of this study was to examine whether the transcription factor ETS1 plays a critical role in the regulation of human decidualization. Decidual fibroblast cells were decidualized in vitro by treatment with medroxyprogesterone, estradiol (E2) and dibutyryl cyclic AMP or prostaglandin E2 in the absence or presence of an ETS1 antisense oligonucleotide (oligo) that blocks the translation of ETS1 mRNA. Control experiments were performed using a control oligo that did not affect ETS1 expression and the induction of specific marker genes for decidualization. The ETS1 antisense oligo markedly inhibited ETS1 protein expression and significantly inhibited downstream targets of ETS1 action. On day 6 of culture, the decidualized fibroblast cells that had been exposed to the ETS1 antisense oligo contained 40-90% less mRNAs for prolactin, insulin growth factor binding protein 1 (IGFBP-1) and other decidualization-specific markers (laminin, tissue inhibitor of metalloproteinase-3 [TIMP3], endometrial bleeding associated factor [EBAF] and decorin) than those of control cells that had not been exposed to the ETS1 antisense oligo. GAPDH mRNA levels, which do not change during decidualization, were unaffected by either the ETS1 antisense or the control oligo. The cells decidualized in the presence of the ETS1 antisense oligo also released significantly less prolactin, EBAF and IGFBP-1 protein, determined by western blot analyses, than the control cells. Taken together, these findings strongly suggest that ETS1 plays a critical role in the induction of human decidualization.
AB - The aim of this study was to examine whether the transcription factor ETS1 plays a critical role in the regulation of human decidualization. Decidual fibroblast cells were decidualized in vitro by treatment with medroxyprogesterone, estradiol (E2) and dibutyryl cyclic AMP or prostaglandin E2 in the absence or presence of an ETS1 antisense oligonucleotide (oligo) that blocks the translation of ETS1 mRNA. Control experiments were performed using a control oligo that did not affect ETS1 expression and the induction of specific marker genes for decidualization. The ETS1 antisense oligo markedly inhibited ETS1 protein expression and significantly inhibited downstream targets of ETS1 action. On day 6 of culture, the decidualized fibroblast cells that had been exposed to the ETS1 antisense oligo contained 40-90% less mRNAs for prolactin, insulin growth factor binding protein 1 (IGFBP-1) and other decidualization-specific markers (laminin, tissue inhibitor of metalloproteinase-3 [TIMP3], endometrial bleeding associated factor [EBAF] and decorin) than those of control cells that had not been exposed to the ETS1 antisense oligo. GAPDH mRNA levels, which do not change during decidualization, were unaffected by either the ETS1 antisense or the control oligo. The cells decidualized in the presence of the ETS1 antisense oligo also released significantly less prolactin, EBAF and IGFBP-1 protein, determined by western blot analyses, than the control cells. Taken together, these findings strongly suggest that ETS1 plays a critical role in the induction of human decidualization.
KW - Decidualization
KW - Differentiation
KW - Gene expression
KW - Pregnancy
KW - Uterus
UR - http://www.scopus.com/inward/record.url?scp=33645518228&partnerID=8YFLogxK
U2 - 10.1093/molehr/gal008
DO - 10.1093/molehr/gal008
M3 - Article
C2 - 16455618
AN - SCOPUS:33645518228
SN - 1360-9947
VL - 12
SP - 71
EP - 76
JO - Molecular human reproduction
JF - Molecular human reproduction
IS - 2
ER -