University of Oulu

Fatima Barragan, Juan C. Irwin, Shaina Balayan, David W. Erikson, Joseph C. Chen, Sahar Houshdaran, Terhi T. Piltonen, Trimble L.B. Spitzer, Ashley George, Joseph T. Rabban, Camran Nezhat, Linda C. Giudice, Human Endometrial Fibroblasts Derived from Mesenchymal Progenitors Inherit Progesterone Resistance and Acquire an Inflammatory Phenotype in the Endometrial Niche in Endometriosis, Biology of Reproduction, Volume 94, Issue 5, 1 May 2016, 118, 1–20,

Human endometrial fibroblasts derived from mesenchymal progenitors inherit progesterone resistance and acquire an inflammatory phenotype in the endometrial niche in endometriosis

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Author: Barragan, Fatima1; Irwin, Juan C.1; Balayan, Shaina1;
Organizations: 1Department of Obstetrics, Gynecology and Reproductive Sciences and the Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California
2Oregon National Primate Research Center/Oregon Health & Science University, Endocrine Technologies Support Core, Beaverton, Oregon
3Siemens Healthcare Diagnostics, Berkeley, California
4Department of Obstetrics and Gynecology and Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
5Reproductive Endocrinology and Infertility Division, Women’s Health, Naval Medical Center, Portsmouth, Virginia
6Department of Animal Sciences, Rutgers University, New Brunswick, New Jersey
7Department of Pathology, University of California, San Francisco, San Francisco, California
8Department of Obstetrics and Gynecology, Stanford University, Stanford, California
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.7 MB)
Persistent link:
Language: English
Published: Oxford University Press, 2016
Publish Date: 2019-08-13


Human endometrium undergoes cyclic regeneration involving stem/progenitor cells, but the role of resident endometrial mesenchymal stem cells (eMSC) as progenitors of endometrial stromal fibroblasts (eSF) has not been definitively demonstrated. In endometriosis, eSF display progesterone (P₄) resistance with impaired decidualization in vivo and in vitro. To investigate eMSC as precursors of eSF and whether endometriosis P₄ resistance is inherited from eMSC, we analyzed transcriptomes of eutopic endometrium eMSC and eSF isolated by fluorescence-activated cell sorting (FACS) from endometriosis (eMSCendo, eSFendo) and controls (eMSCcontrol, eSFcontrol) and their derived primary cultures. Differentially expressed lineage-associated genes (LG) of FACS-isolated eMSC and eSF were largely conserved in endometriosis. In culture, eSFcontrol maintained in vitro expression of a subset of eSF LG and decidualized in vitro with P₄. The eMSCcontrol cultures differentiated in vitro to eSF lineage, down-regulating eMSC LG and up-regulating eSF LG, showing minimal transcriptome differences versus eSFcontrol cultures and decidualizing in vitro. Cultured eSFendo displayed less in vitro LG stability and did not decidualize in vitro. In vitro, eMSCendo differentiated to eSF lineage but showed more differentially expressed genes versus eSFendo cultures, and did not decidualize in vitro, demonstrating P₄ resistance inherited from eMSCendo. Compared to controls, cultures from tissue-derived eSFendo uniquely had a pro-inflammatory phenotype not present in eMSCendo differentiated to eSF in vitro, suggesting divergent niche effects for in vivo versus in vitro lineage differentiation. These findings substantiate eMSC as progenitors of eSF and reveal eSF in endometriosis as having P₄ resistance inherited from eMSC and a pro-inflammatory phenotype acquired within the endometrial niche.

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Series: Biology of reproduction
ISSN: 0006-3363
ISSN-E: 1529-7268
ISSN-L: 0006-3363
Volume: 94
Issue: 5
Article number: 118
DOI: 10.1095/biolreprod.115.136010
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)/NIH National Centers for Translational Research in Reproduction and Infertility P50 HD 055764-09 (L.C.G.).
Copyright information: © 2016 by the Society for the Study of Reproduction, Inc. This is an Open Access article, freely available through Biology of Reproduction’s Authors’ Choice option, and is available under a Creative Commons License 4.0 (Attribution-Non-Commercial), as described at