Pro-inflammatory cytokine-stimulated first trimester decidual cells enhance macrophage-induced apoptosis of extravillous trophoblasts

Wu, Z.-M.; Yang, H.; Li, M.; Yeh, C.-C.; Schatz, F.; Lockwood, C.J.; Di, W.; Huang, S.J.

doi:10.1016/j.placenta.2011.12.007

« Previous Next »Placenta
Volume 33, Issue 3 , Pages 188-194, March 2012

Pro-inflammatory cytokine-stimulated first trimester decidual cells enhance macrophage-induced apoptosis of extravillous trophoblasts

Z.-M. Wu
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, 333 Cedar St., P. O. Box 208063, New Haven, CT 06520, USA
- Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University, Shanghai 200127, PR China
- ZMW and HY equally contributed to this study.
H. Yang
- Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University, Shanghai 200127, PR China
- Department of Genetics, Yale University, New Haven, CT 06520, USA
- ZMW and HY equally contributed to this study.
M. Li
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, 333 Cedar St., P. O. Box 208063, New Haven, CT 06520, USA
C.-C. Yeh
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, 333 Cedar St., P. O. Box 208063, New Haven, CT 06520, USA
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan
F. Schatz
- College of Medicine, Ohio State University, Columbus, OH 43210, USA
C.J. Lockwood
- College of Medicine, Ohio State University, Columbus, OH 43210, USA
W. Di
- Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University, Shanghai 200127, PR China
S.J. Huang
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, 333 Cedar St., P. O. Box 208063, New Haven, CT 06520, USA
- Corresponding author. Tel.: +1 203 737 2394; fax: +1 203 737 5618.

Accepted 9 December 2011. published online 04 January 2012.

Abstract

Objective

As human blastocyst-derived extravillous trophoblasts (EVTs) invade the early decidua, they are positioned to interact with immune cells and resident decidual cells, and remodel spiral arteries into high capacity vessels that increase blood flow to the developing fetal-placental unit. Shallow EVT invasion elicits incomplete vascular transformation and reduces uteroplacental blood flow that presages adverse pregnancy outcomes. Excess macrophages in the decidua induce EVT apoptosis via tumor necrosis factor-alpha (TNF-α) secretion. Our previous observation that pro-inflammatory cytokines enhance neutrophil and macrophage activator granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in first trimester decidual cells is now extended to include: 1) the specific macrophage activator M-CSF; 2) macrophage activation and subsequent enhancement of EVT apoptosis by both GM-CSF and M-CSF.

Study design

Quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay assessed M-CSF expression in first trimester decidual cells incubated with interleukin-1 beta (IL-1β) or TNF-α. Peripheral monocyte-derived macrophages pre-incubated with conditioned media from decidual cell cultures were co-cultured with a first trimester EVT cell line, HTR-8/SVneo cells. Macrophage activation was examined and EVT apoptosis evaluated by DNA fragmentation, caspase activation and cell membrane asymmetry.

Results

IL-1β or TNF-α significantly enhanced M-CSF expression in first trimester decidual cells. The conditioned media from these cultures activates macrophages, which promote caspase 3/7-dependent EVT apoptosis with antibodies against GM-CSF or M-CSF blocking this effect.

Conclusions

Pro-inflammatory cytokines increases synthesis of M-CSF in first trimester decidual cells. Both GM-CSF and M-CSF activate macrophages, which initiate caspase-dependent EVT apoptosis.

Keywords: First trimester decidual cells, Macrophage, Extravillous trophoblast, Apoptosis, GM-CSF, M-CSF