Mesenchymal Stem Cells-Induced Trophoblast Invasion Is Reduced in Patients with a Previous History of Preeclampsia

Reyna Peñailillo; Stephanie Acuña-Gallardo; Felipe García; Lara J. Monteiro; Gino Nardocci; Mahesh A. Choolani; Matthew W. Kemp; Roberto Romero; Sebastián E. Illanes

doi:10.3390/ijms23169071

Mesenchymal Stem Cells-Induced Trophoblast Invasion Is Reduced in Patients with a Previous History of Preeclampsia

Reyna Peñailillo, Stephanie Acuña-Gallardo, Felipe García, Lara J. Monteiro, Gino Nardocci, Mahesh A. Choolani, Matthew W. Kemp, Roberto Romero, Sebastián E. Illanes^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Endometrial stromal cells play an important role in reproductive success, especially in implantation and placentation. Although Mesenchymal stem cells (MSCs) have been studied to assess decidualization disorders in preeclampsia (PE), their role during trophoblast invasion remains unclear. This study aims to determine: (i) whether MSCs isolated from menstrual fluid (MenSCs) from nulliparous, multiparous, and women with a previous history of preeclampsia exhibited different patterns of proliferation and migration and (ii) whether reproductive history (i.e., prior pregnancy or prior history of PE) was able to produce changes in MenSCs, thus altering trophoblast invasion capacity. MenSCs were collected from nulliparous and multiparous women without a history of PE and from non-pregnant women with a history of PE. Proliferation and migration assays were performed on MenSCs with sulforhodamine B and transwell assays, respectively. Trophoblast invasion was analyzed by culturing HTR-8/SVneo trophospheres on a matrigel overlying MenSCs for 72 h at 5% O₂, simulating a 3D implantation model. A previous history of pregnancy or PE did not impact the proliferative capacity or migratory behavior of MenSCs. Following exposure to physiological endometrial conditions, MenSCs demonstrated upregulated expression of IGFBP-1 and LIF mRNA, decidualization and window of implantation markers, respectively. The mRNA expression of VIM, NANOG, and SOX2 was upregulated upon trophosphere formation. Relative to co-culture with multiparous MenSCs, co-culture with PE-MenSCs was associated with reduced trophoblast invasion. The findings of this study suggest a potential role for communication between maternal MenSCs and invading trophoblast cells during the implantation process that could be implicated in the etiology of PE.

Original language	English
Article number	9071
Journal	International Journal of Molecular Sciences
Volume	23
Issue number	16
DOIs	https://doi.org/10.3390/ijms23169071
State	Published - 13 Aug 2022

Bibliographical note

Funding Information:
This research was funded by ANID/CONICYT—FONDECYT Regular 1201851 (to S.E.I.); ANID/CONICYT—FONDECYT de Iniciación 11190998 (to G.N.) and ANID/CONICYT—FONDECYT de Iniciación 11181249 (to L.J.M.); ANID-BASAL funding for Scientific and Technological Center of Excellence, IMPACT, #FB210024 (to L.J.M, G.N. and S.E.I.). This study was also supported, in part, by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services (NICHD/NIH/DHHS); and, in part, with Federal funds from NICHD/NIH/DHHS under Contract No. HHSN275201300006C. R.R. has contributed to this work as part of his official duties as an employee of the United States Federal Government.

Publisher Copyright:
© 2022 by the authors.

Keywords

Cell Movement/genetics
Cell Proliferation
Female
Humans
Mesenchymal Stem Cells/metabolism
Pre-Eclampsia/metabolism
Pregnancy
RNA, Messenger/metabolism
Trophoblasts/metabolism

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title = "Mesenchymal Stem Cells-Induced Trophoblast Invasion Is Reduced in Patients with a Previous History of Preeclampsia",

abstract = "Endometrial stromal cells play an important role in reproductive success, especially in implantation and placentation. Although Mesenchymal stem cells (MSCs) have been studied to assess decidualization disorders in preeclampsia (PE), their role during trophoblast invasion remains unclear. This study aims to determine: (i) whether MSCs isolated from menstrual fluid (MenSCs) from nulliparous, multiparous, and women with a previous history of preeclampsia exhibited different patterns of proliferation and migration and (ii) whether reproductive history (i.e., prior pregnancy or prior history of PE) was able to produce changes in MenSCs, thus altering trophoblast invasion capacity. MenSCs were collected from nulliparous and multiparous women without a history of PE and from non-pregnant women with a history of PE. Proliferation and migration assays were performed on MenSCs with sulforhodamine B and transwell assays, respectively. Trophoblast invasion was analyzed by culturing HTR-8/SVneo trophospheres on a matrigel overlying MenSCs for 72 h at 5% O2, simulating a 3D implantation model. A previous history of pregnancy or PE did not impact the proliferative capacity or migratory behavior of MenSCs. Following exposure to physiological endometrial conditions, MenSCs demonstrated upregulated expression of IGFBP-1 and LIF mRNA, decidualization and window of implantation markers, respectively. The mRNA expression of VIM, NANOG, and SOX2 was upregulated upon trophosphere formation. Relative to co-culture with multiparous MenSCs, co-culture with PE-MenSCs was associated with reduced trophoblast invasion. The findings of this study suggest a potential role for communication between maternal MenSCs and invading trophoblast cells during the implantation process that could be implicated in the etiology of PE.",

keywords = "Cell Movement/genetics, Cell Proliferation, Female, Humans, Mesenchymal Stem Cells/metabolism, Pre-Eclampsia/metabolism, Pregnancy, RNA, Messenger/metabolism, Trophoblasts/metabolism",

author = "Reyna Pe{\~n}ailillo and Stephanie Acu{\~n}a-Gallardo and Felipe Garc{\'i}a and Monteiro, {Lara J.} and Gino Nardocci and Choolani, {Mahesh A.} and Kemp, {Matthew W.} and Roberto Romero and Illanes, {Sebasti{\'a}n E.}",

note = "Funding Information: This research was funded by ANID/CONICYT—FONDECYT Regular 1201851 (to S.E.I.); ANID/CONICYT—FONDECYT de Iniciaci{\'o}n 11190998 (to G.N.) and ANID/CONICYT—FONDECYT de Iniciaci{\'o}n 11181249 (to L.J.M.); ANID-BASAL funding for Scientific and Technological Center of Excellence, IMPACT, #FB210024 (to L.J.M, G.N. and S.E.I.). This study was also supported, in part, by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services (NICHD/NIH/DHHS); and, in part, with Federal funds from NICHD/NIH/DHHS under Contract No. HHSN275201300006C. R.R. has contributed to this work as part of his official duties as an employee of the United States Federal Government. Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = aug,

day = "13",

doi = "10.3390/ijms23169071",

language = "English",

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T1 - Mesenchymal Stem Cells-Induced Trophoblast Invasion Is Reduced in Patients with a Previous History of Preeclampsia

AU - Peñailillo, Reyna

AU - Acuña-Gallardo, Stephanie

AU - García, Felipe

AU - Monteiro, Lara J.

AU - Nardocci, Gino

AU - Choolani, Mahesh A.

AU - Kemp, Matthew W.

AU - Romero, Roberto

AU - Illanes, Sebastián E.

N1 - Funding Information: This research was funded by ANID/CONICYT—FONDECYT Regular 1201851 (to S.E.I.); ANID/CONICYT—FONDECYT de Iniciación 11190998 (to G.N.) and ANID/CONICYT—FONDECYT de Iniciación 11181249 (to L.J.M.); ANID-BASAL funding for Scientific and Technological Center of Excellence, IMPACT, #FB210024 (to L.J.M, G.N. and S.E.I.). This study was also supported, in part, by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services (NICHD/NIH/DHHS); and, in part, with Federal funds from NICHD/NIH/DHHS under Contract No. HHSN275201300006C. R.R. has contributed to this work as part of his official duties as an employee of the United States Federal Government. Publisher Copyright: © 2022 by the authors.

PY - 2022/8/13

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N2 - Endometrial stromal cells play an important role in reproductive success, especially in implantation and placentation. Although Mesenchymal stem cells (MSCs) have been studied to assess decidualization disorders in preeclampsia (PE), their role during trophoblast invasion remains unclear. This study aims to determine: (i) whether MSCs isolated from menstrual fluid (MenSCs) from nulliparous, multiparous, and women with a previous history of preeclampsia exhibited different patterns of proliferation and migration and (ii) whether reproductive history (i.e., prior pregnancy or prior history of PE) was able to produce changes in MenSCs, thus altering trophoblast invasion capacity. MenSCs were collected from nulliparous and multiparous women without a history of PE and from non-pregnant women with a history of PE. Proliferation and migration assays were performed on MenSCs with sulforhodamine B and transwell assays, respectively. Trophoblast invasion was analyzed by culturing HTR-8/SVneo trophospheres on a matrigel overlying MenSCs for 72 h at 5% O2, simulating a 3D implantation model. A previous history of pregnancy or PE did not impact the proliferative capacity or migratory behavior of MenSCs. Following exposure to physiological endometrial conditions, MenSCs demonstrated upregulated expression of IGFBP-1 and LIF mRNA, decidualization and window of implantation markers, respectively. The mRNA expression of VIM, NANOG, and SOX2 was upregulated upon trophosphere formation. Relative to co-culture with multiparous MenSCs, co-culture with PE-MenSCs was associated with reduced trophoblast invasion. The findings of this study suggest a potential role for communication between maternal MenSCs and invading trophoblast cells during the implantation process that could be implicated in the etiology of PE.

AB - Endometrial stromal cells play an important role in reproductive success, especially in implantation and placentation. Although Mesenchymal stem cells (MSCs) have been studied to assess decidualization disorders in preeclampsia (PE), their role during trophoblast invasion remains unclear. This study aims to determine: (i) whether MSCs isolated from menstrual fluid (MenSCs) from nulliparous, multiparous, and women with a previous history of preeclampsia exhibited different patterns of proliferation and migration and (ii) whether reproductive history (i.e., prior pregnancy or prior history of PE) was able to produce changes in MenSCs, thus altering trophoblast invasion capacity. MenSCs were collected from nulliparous and multiparous women without a history of PE and from non-pregnant women with a history of PE. Proliferation and migration assays were performed on MenSCs with sulforhodamine B and transwell assays, respectively. Trophoblast invasion was analyzed by culturing HTR-8/SVneo trophospheres on a matrigel overlying MenSCs for 72 h at 5% O2, simulating a 3D implantation model. A previous history of pregnancy or PE did not impact the proliferative capacity or migratory behavior of MenSCs. Following exposure to physiological endometrial conditions, MenSCs demonstrated upregulated expression of IGFBP-1 and LIF mRNA, decidualization and window of implantation markers, respectively. The mRNA expression of VIM, NANOG, and SOX2 was upregulated upon trophosphere formation. Relative to co-culture with multiparous MenSCs, co-culture with PE-MenSCs was associated with reduced trophoblast invasion. The findings of this study suggest a potential role for communication between maternal MenSCs and invading trophoblast cells during the implantation process that could be implicated in the etiology of PE.

KW - Cell Movement/genetics

KW - Cell Proliferation

KW - Female

KW - Humans

KW - Mesenchymal Stem Cells/metabolism

KW - Pre-Eclampsia/metabolism

KW - Pregnancy

KW - RNA, Messenger/metabolism

KW - Trophoblasts/metabolism

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SN - 1661-6596

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 16

M1 - 9071

ER -

Mesenchymal Stem Cells-Induced Trophoblast Invasion Is Reduced in Patients with a Previous History of Preeclampsia

Abstract

Bibliographical note

Keywords

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