Thrombin Alters Human Endometrial Stromal Cell Differentiation During Decidualization

Research output: Contribution to journalArticle

Abstract

Vaginal bleeding and subchorionic hematomas are associated with increased risk of both early and late pregnancy loss. Thrombin generation may play a pivotal role in the development of these complications. To determine the effects of thrombin on human endometrial stromal cells (hESCs), cells were treated with thrombin at baseline or during decidualization with cyclic adenosine monophosphate (cAMP)+medroxyprogesterone acetate (MPA). Next-generation RNA sequencing revealed that markers of decidualization (IGF-1, IGFBP-1, and prolactin [PRL]) were induced after the initiation of decidualization, whereas thrombin suppressed insulin-like growth factor (IGF)-1, Insulin-like growth factor binding protein (IGFBP)-1, and PRL gene expression at baseline and during decidualization. These effects were mediated through protease activated receptor (PAR)-1- and PAR-1-independent pathways. Thrombin decreased the secretion of a key marker of decidualization (PRL), altered the morphological transformation of decidualizing hESCs, and activated genes involved in matrix degradation and proinflammatory chemokines (Interleukin-8 and Interleukin-6). Genes encoding factors important for matrix stability (Col1α1, LOX) were suppressed. We suggest that intrauterine bleeding and generation of thrombin accentuates leukocyte extravasation and endometrial inflammation, impairs decidualization, and endometrial support of early pregnancy.

Original languageEnglish (US)
JournalReproductive Sciences
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Stromal Cells
Thrombin
Cell Differentiation
PAR-1 Receptor
Prolactin
Insulin-Like Growth Factor Binding Protein 1
Somatomedins
RNA Sequence Analysis
Pregnancy
Medroxyprogesterone Acetate
Uterine Hemorrhage
Interleukin-8
Chemokines
Hematoma
Cyclic AMP
Genes
Interleukin-6
Leukocytes
Hemorrhage
Inflammation

Keywords

  • endometrium
  • inflammation
  • menstrual bleeding
  • prolactin
  • protease
  • RNAseq

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

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title = "Thrombin Alters Human Endometrial Stromal Cell Differentiation During Decidualization",
abstract = "Vaginal bleeding and subchorionic hematomas are associated with increased risk of both early and late pregnancy loss. Thrombin generation may play a pivotal role in the development of these complications. To determine the effects of thrombin on human endometrial stromal cells (hESCs), cells were treated with thrombin at baseline or during decidualization with cyclic adenosine monophosphate (cAMP)+medroxyprogesterone acetate (MPA). Next-generation RNA sequencing revealed that markers of decidualization (IGF-1, IGFBP-1, and prolactin [PRL]) were induced after the initiation of decidualization, whereas thrombin suppressed insulin-like growth factor (IGF)-1, Insulin-like growth factor binding protein (IGFBP)-1, and PRL gene expression at baseline and during decidualization. These effects were mediated through protease activated receptor (PAR)-1- and PAR-1-independent pathways. Thrombin decreased the secretion of a key marker of decidualization (PRL), altered the morphological transformation of decidualizing hESCs, and activated genes involved in matrix degradation and proinflammatory chemokines (Interleukin-8 and Interleukin-6). Genes encoding factors important for matrix stability (Col1α1, LOX) were suppressed. We suggest that intrauterine bleeding and generation of thrombin accentuates leukocyte extravasation and endometrial inflammation, impairs decidualization, and endometrial support of early pregnancy.",
keywords = "endometrium, inflammation, menstrual bleeding, prolactin, protease, RNAseq",
author = "Babayev, {Samir N.} and Mohammed Kanchwala and Chao Xing and Yucel Akgul and Carr, {Bruce R.} and Word, {Ruth Ann}",
year = "2018",
month = "1",
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doi = "10.1177/1933719118768705",
language = "English (US)",
journal = "Reproductive Sciences",
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T1 - Thrombin Alters Human Endometrial Stromal Cell Differentiation During Decidualization

AU - Babayev, Samir N.

AU - Kanchwala, Mohammed

AU - Xing, Chao

AU - Akgul, Yucel

AU - Carr, Bruce R.

AU - Word, Ruth Ann

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Vaginal bleeding and subchorionic hematomas are associated with increased risk of both early and late pregnancy loss. Thrombin generation may play a pivotal role in the development of these complications. To determine the effects of thrombin on human endometrial stromal cells (hESCs), cells were treated with thrombin at baseline or during decidualization with cyclic adenosine monophosphate (cAMP)+medroxyprogesterone acetate (MPA). Next-generation RNA sequencing revealed that markers of decidualization (IGF-1, IGFBP-1, and prolactin [PRL]) were induced after the initiation of decidualization, whereas thrombin suppressed insulin-like growth factor (IGF)-1, Insulin-like growth factor binding protein (IGFBP)-1, and PRL gene expression at baseline and during decidualization. These effects were mediated through protease activated receptor (PAR)-1- and PAR-1-independent pathways. Thrombin decreased the secretion of a key marker of decidualization (PRL), altered the morphological transformation of decidualizing hESCs, and activated genes involved in matrix degradation and proinflammatory chemokines (Interleukin-8 and Interleukin-6). Genes encoding factors important for matrix stability (Col1α1, LOX) were suppressed. We suggest that intrauterine bleeding and generation of thrombin accentuates leukocyte extravasation and endometrial inflammation, impairs decidualization, and endometrial support of early pregnancy.

AB - Vaginal bleeding and subchorionic hematomas are associated with increased risk of both early and late pregnancy loss. Thrombin generation may play a pivotal role in the development of these complications. To determine the effects of thrombin on human endometrial stromal cells (hESCs), cells were treated with thrombin at baseline or during decidualization with cyclic adenosine monophosphate (cAMP)+medroxyprogesterone acetate (MPA). Next-generation RNA sequencing revealed that markers of decidualization (IGF-1, IGFBP-1, and prolactin [PRL]) were induced after the initiation of decidualization, whereas thrombin suppressed insulin-like growth factor (IGF)-1, Insulin-like growth factor binding protein (IGFBP)-1, and PRL gene expression at baseline and during decidualization. These effects were mediated through protease activated receptor (PAR)-1- and PAR-1-independent pathways. Thrombin decreased the secretion of a key marker of decidualization (PRL), altered the morphological transformation of decidualizing hESCs, and activated genes involved in matrix degradation and proinflammatory chemokines (Interleukin-8 and Interleukin-6). Genes encoding factors important for matrix stability (Col1α1, LOX) were suppressed. We suggest that intrauterine bleeding and generation of thrombin accentuates leukocyte extravasation and endometrial inflammation, impairs decidualization, and endometrial support of early pregnancy.

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