title: cAMP-Response Element-Binding 3-Like Protein 1 (CREB3L1) is Required for Decidualization and its Expression is Decreased in Women with Endometriosis.
abstract: Endometriosis is a major cause of infertility and pelvic pain, affecting more than 10% of reproductive-aged women. Progesterone resistance has been observed in the endometrium of women with this disease, as evidenced by alterations in progesterone-responsive gene and protein expression. cAMPResponse Element-Binding 3-like protein 1 (Creb3l1) has previously been identified as a progesterone receptor (PR) target gene in mouse uterus via high density DNA microarray analysis. However, CREB3L1 function has not been studied in the context of endometriosis and uterine biology. In this study, we validated progesterone (P4) regulation of Creb3l1 in the uteri of wild-type and progesterone receptor knockout (PRKO) mice. Furthermore, we observed that CREB3L1 expression was significantly higher in secretory phase human endometrium compared to proliferative phase and that CREB3L1 expression was significantly decreased in the endometrium of women with endometriosis. Lastly, by transfecting CREB3L1 siRNA into cultured human endometrial stromal cells (hESCs) prior to hormonal induction of in vitro decidualization, we showed that CREB3L1 is required for the decidualization process. Interestingly, phosphorylation of ERK1/2, critical factor for decidualization, was also significantly reduced in CREB3L1-silenced hESCs. It is known that hESCs from patients with endometriosis show impaired decidualization and that dysregulation of the P4-PR signaling axis is linked to a variety of endometrial diseases including infertility and endometriosis. Therefore, these results suggest that CREB3L1 is required for decidualization in mice and humans and may be linked to the pathogenesis of endometriosis in a P4-dependent manner.
authors.forename: J I
authors.initials: JI
authors.lastname: Ahn
authors.forename: J-Y
authors.initials: JY
authors.lastname: Yoo
authors.forename: T H
authors.initials: TH
authors.lastname: Kim
authors.forename: Y I
authors.initials: YI
authors.lastname: Kim
authors.forename: S D
authors.initials: SD
authors.lastname: Ferguson
authors.forename: A T
authors.initials: AT
authors.lastname: Fazleabas
authors.forename: S L
authors.initials: SL
authors.lastname: Young
authors.forename: B A
authors.initials: BA
authors.lastname: Lessey
authors.forename: J Y
authors.initials: JY
authors.lastname: Ahn
authors.affiliation: Laboratory of Stem Cell and Bioevaluation, Major in Biomodulation, Seoul National University, Seoul 151-921, Republic of Korea. limjm@snu.ac.kr.
authors.forename: J M
authors.initials: JM
authors.lastname: Lim
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, College of Human Medicine, 333 Bostwick Avenue NE, Suite 4024, Grand Rapids, MI 49503, USA. JaeWook.Jeong@hc.msu.edu.
authors.forename: J-W
authors.initials: JW
authors.lastname: Jeong
mesh_terms: D000328:Adult; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004715:Endometriosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007044:Hysterectomy; D008597:Menstrual Cycle / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D011374:Progesterone / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000172:deficiency / Q000235:genetics*; D015398:Signal Transduction; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: C485618:CREB3L1 protein, human; C119923:Creb3l1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D011980:Receptors, Progesterone; D011374:Progesterone; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3