Cargando…
Matrix metalloproteinase 15 plays a pivotal role in human first trimester cytotrophoblast invasion and is not altered by maternal obesity
Adequate anchoring of the placenta in the uterus through invasion of first trimester cytotrophoblasts (CTB) is required for a successful pregnancy. This process is mediated by matrix metalloproteinases (MMPs) and regulated by the maternal environment. Obesity is known to alter the intrauterine milie...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496590/ https://www.ncbi.nlm.nih.gov/pubmed/32614494 http://dx.doi.org/10.1096/fj.202000773R |
_version_ | 1783583131981316096 |
---|---|
author | Majali‐Martinez, Alejandro Hoch, Denise Tam‐Amersdorfer, Carmen Pollheimer, Jürgen Glasner, Andreas Ghaffari‐Tabrizi‐Wizsy, Nassim Beristain, Alexander G. Hiden, Ursula Dieber‐Rotheneder, Martina Desoye, Gernot |
author_facet | Majali‐Martinez, Alejandro Hoch, Denise Tam‐Amersdorfer, Carmen Pollheimer, Jürgen Glasner, Andreas Ghaffari‐Tabrizi‐Wizsy, Nassim Beristain, Alexander G. Hiden, Ursula Dieber‐Rotheneder, Martina Desoye, Gernot |
author_sort | Majali‐Martinez, Alejandro |
collection | PubMed |
description | Adequate anchoring of the placenta in the uterus through invasion of first trimester cytotrophoblasts (CTB) is required for a successful pregnancy. This process is mediated by matrix metalloproteinases (MMPs) and regulated by the maternal environment. Obesity is known to alter the intrauterine milieu and has been related to impaired invasion. We hypothesized that placental MMP15, a novel membrane‐type MMP, is involved in CTB invasion and regulated by maternal obesity in early pregnancy. Thus, in this study MMP15 was immunolocalized to invasive extravillous and interstitial CTB. MMP15 silencing in chorionic villous explants using two different siRNAs reduced trophoblast outgrowth length (−35%, P ≤ .001 and −26%, P < .05) and area (−43%, P ≤ .001 and −36%, P ≤ .01) without altering trophoblast proliferation or apoptosis. Short‐term treatment of primary first trimester trophoblasts with IL‐6 (10 ng/mL), interleukin 10 (IL‐10) (50 ng/mL), and tumor necrosis factor α (TNF‐α) (10 ng/mL) did not affect MMP15 protein levels. Likewise, MMP15 mRNA and protein levels were unaltered between human first trimester placentas from control pregnancies vs those complicated with maternal obesity. Overall, our results suggest that the role of MMP15 in placental development and function in early pregnancy is limited to CTB invasion without being affected by short‐ and long‐term inflammation. |
format | Online Article Text |
id | pubmed-7496590 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74965902020-09-25 Matrix metalloproteinase 15 plays a pivotal role in human first trimester cytotrophoblast invasion and is not altered by maternal obesity Majali‐Martinez, Alejandro Hoch, Denise Tam‐Amersdorfer, Carmen Pollheimer, Jürgen Glasner, Andreas Ghaffari‐Tabrizi‐Wizsy, Nassim Beristain, Alexander G. Hiden, Ursula Dieber‐Rotheneder, Martina Desoye, Gernot FASEB J Research Articles Adequate anchoring of the placenta in the uterus through invasion of first trimester cytotrophoblasts (CTB) is required for a successful pregnancy. This process is mediated by matrix metalloproteinases (MMPs) and regulated by the maternal environment. Obesity is known to alter the intrauterine milieu and has been related to impaired invasion. We hypothesized that placental MMP15, a novel membrane‐type MMP, is involved in CTB invasion and regulated by maternal obesity in early pregnancy. Thus, in this study MMP15 was immunolocalized to invasive extravillous and interstitial CTB. MMP15 silencing in chorionic villous explants using two different siRNAs reduced trophoblast outgrowth length (−35%, P ≤ .001 and −26%, P < .05) and area (−43%, P ≤ .001 and −36%, P ≤ .01) without altering trophoblast proliferation or apoptosis. Short‐term treatment of primary first trimester trophoblasts with IL‐6 (10 ng/mL), interleukin 10 (IL‐10) (50 ng/mL), and tumor necrosis factor α (TNF‐α) (10 ng/mL) did not affect MMP15 protein levels. Likewise, MMP15 mRNA and protein levels were unaltered between human first trimester placentas from control pregnancies vs those complicated with maternal obesity. Overall, our results suggest that the role of MMP15 in placental development and function in early pregnancy is limited to CTB invasion without being affected by short‐ and long‐term inflammation. John Wiley and Sons Inc. 2020-07-02 2020-08 /pmc/articles/PMC7496590/ /pubmed/32614494 http://dx.doi.org/10.1096/fj.202000773R Text en © 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Majali‐Martinez, Alejandro Hoch, Denise Tam‐Amersdorfer, Carmen Pollheimer, Jürgen Glasner, Andreas Ghaffari‐Tabrizi‐Wizsy, Nassim Beristain, Alexander G. Hiden, Ursula Dieber‐Rotheneder, Martina Desoye, Gernot Matrix metalloproteinase 15 plays a pivotal role in human first trimester cytotrophoblast invasion and is not altered by maternal obesity |
title | Matrix metalloproteinase 15 plays a pivotal role in human first trimester cytotrophoblast invasion and is not altered by maternal obesity |
title_full | Matrix metalloproteinase 15 plays a pivotal role in human first trimester cytotrophoblast invasion and is not altered by maternal obesity |
title_fullStr | Matrix metalloproteinase 15 plays a pivotal role in human first trimester cytotrophoblast invasion and is not altered by maternal obesity |
title_full_unstemmed | Matrix metalloproteinase 15 plays a pivotal role in human first trimester cytotrophoblast invasion and is not altered by maternal obesity |
title_short | Matrix metalloproteinase 15 plays a pivotal role in human first trimester cytotrophoblast invasion and is not altered by maternal obesity |
title_sort | matrix metalloproteinase 15 plays a pivotal role in human first trimester cytotrophoblast invasion and is not altered by maternal obesity |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496590/ https://www.ncbi.nlm.nih.gov/pubmed/32614494 http://dx.doi.org/10.1096/fj.202000773R |
work_keys_str_mv | AT majalimartinezalejandro matrixmetalloproteinase15playsapivotalroleinhumanfirsttrimestercytotrophoblastinvasionandisnotalteredbymaternalobesity AT hochdenise matrixmetalloproteinase15playsapivotalroleinhumanfirsttrimestercytotrophoblastinvasionandisnotalteredbymaternalobesity AT tamamersdorfercarmen matrixmetalloproteinase15playsapivotalroleinhumanfirsttrimestercytotrophoblastinvasionandisnotalteredbymaternalobesity AT pollheimerjurgen matrixmetalloproteinase15playsapivotalroleinhumanfirsttrimestercytotrophoblastinvasionandisnotalteredbymaternalobesity AT glasnerandreas matrixmetalloproteinase15playsapivotalroleinhumanfirsttrimestercytotrophoblastinvasionandisnotalteredbymaternalobesity AT ghaffaritabriziwizsynassim matrixmetalloproteinase15playsapivotalroleinhumanfirsttrimestercytotrophoblastinvasionandisnotalteredbymaternalobesity AT beristainalexanderg matrixmetalloproteinase15playsapivotalroleinhumanfirsttrimestercytotrophoblastinvasionandisnotalteredbymaternalobesity AT hidenursula matrixmetalloproteinase15playsapivotalroleinhumanfirsttrimestercytotrophoblastinvasionandisnotalteredbymaternalobesity AT dieberrothenedermartina matrixmetalloproteinase15playsapivotalroleinhumanfirsttrimestercytotrophoblastinvasionandisnotalteredbymaternalobesity AT desoyegernot matrixmetalloproteinase15playsapivotalroleinhumanfirsttrimestercytotrophoblastinvasionandisnotalteredbymaternalobesity |