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Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction

Biomarkers for placental dysfunction are currently lacking. We recently identified SPINT1 as a novel biomarker; SPINT2 is a functionally related placental protease inhibitor. This study aimed to characterise SPINT2 expression in placental insufficiency. Circulating SPINT2 was assessed in three prosp...

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Autores principales: Murphy, Ciara N., Walker, Susan P., MacDonald, Teresa M., Keenan, Emerson, Hannan, Natalie J., Wlodek, Mary E., Myers, Jenny, Briffa, Jessica F., Romano, Tania, Roddy Mitchell, Alexandra, Whigham, Carole-Anne, Cannon, Ping, Nguyen, Tuong-Vi, Kandel, Manju, Pritchard, Natasha, Tong, Stephen, Kaitu’u-Lino, Tu’uhevaha J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305184/
https://www.ncbi.nlm.nih.gov/pubmed/34299087
http://dx.doi.org/10.3390/ijms22147467
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author Murphy, Ciara N.
Walker, Susan P.
MacDonald, Teresa M.
Keenan, Emerson
Hannan, Natalie J.
Wlodek, Mary E.
Myers, Jenny
Briffa, Jessica F.
Romano, Tania
Roddy Mitchell, Alexandra
Whigham, Carole-Anne
Cannon, Ping
Nguyen, Tuong-Vi
Kandel, Manju
Pritchard, Natasha
Tong, Stephen
Kaitu’u-Lino, Tu’uhevaha J.
author_facet Murphy, Ciara N.
Walker, Susan P.
MacDonald, Teresa M.
Keenan, Emerson
Hannan, Natalie J.
Wlodek, Mary E.
Myers, Jenny
Briffa, Jessica F.
Romano, Tania
Roddy Mitchell, Alexandra
Whigham, Carole-Anne
Cannon, Ping
Nguyen, Tuong-Vi
Kandel, Manju
Pritchard, Natasha
Tong, Stephen
Kaitu’u-Lino, Tu’uhevaha J.
author_sort Murphy, Ciara N.
collection PubMed
description Biomarkers for placental dysfunction are currently lacking. We recently identified SPINT1 as a novel biomarker; SPINT2 is a functionally related placental protease inhibitor. This study aimed to characterise SPINT2 expression in placental insufficiency. Circulating SPINT2 was assessed in three prospective cohorts, collected at the following: (1) term delivery (n = 227), (2) 36 weeks (n = 364), and (3) 24–34 weeks’ (n = 294) gestation. SPINT2 was also measured in the plasma and placentas of women with established placental disease at preterm (<34 weeks) delivery. Using first-trimester human trophoblast stem cells, SPINT2 expression was assessed in hypoxia/normoxia (1% vs. 8% O2), and following inflammatory cytokine treatment (TNFα, IL-6). Placental SPINT2 mRNA was measured in a rat model of late-gestational foetal growth restriction. At 36 weeks, circulating SPINT2 was elevated in patients who later developed preeclampsia (p = 0.028; median = 2233 pg/mL vs. controls, median = 1644 pg/mL), or delivered a small-for-gestational-age infant (p = 0.002; median = 2109 pg/mL vs. controls, median = 1614 pg/mL). SPINT2 was elevated in the placentas of patients who required delivery for preterm preeclampsia (p = 0.025). Though inflammatory cytokines had no effect, hypoxia increased SPINT2 in cytotrophoblast stem cells, and its expression was elevated in the placental labyrinth of growth-restricted rats. These findings suggest elevated SPINT2 is associated with placental insufficiency.
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spelling pubmed-83051842021-07-25 Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction Murphy, Ciara N. Walker, Susan P. MacDonald, Teresa M. Keenan, Emerson Hannan, Natalie J. Wlodek, Mary E. Myers, Jenny Briffa, Jessica F. Romano, Tania Roddy Mitchell, Alexandra Whigham, Carole-Anne Cannon, Ping Nguyen, Tuong-Vi Kandel, Manju Pritchard, Natasha Tong, Stephen Kaitu’u-Lino, Tu’uhevaha J. Int J Mol Sci Article Biomarkers for placental dysfunction are currently lacking. We recently identified SPINT1 as a novel biomarker; SPINT2 is a functionally related placental protease inhibitor. This study aimed to characterise SPINT2 expression in placental insufficiency. Circulating SPINT2 was assessed in three prospective cohorts, collected at the following: (1) term delivery (n = 227), (2) 36 weeks (n = 364), and (3) 24–34 weeks’ (n = 294) gestation. SPINT2 was also measured in the plasma and placentas of women with established placental disease at preterm (<34 weeks) delivery. Using first-trimester human trophoblast stem cells, SPINT2 expression was assessed in hypoxia/normoxia (1% vs. 8% O2), and following inflammatory cytokine treatment (TNFα, IL-6). Placental SPINT2 mRNA was measured in a rat model of late-gestational foetal growth restriction. At 36 weeks, circulating SPINT2 was elevated in patients who later developed preeclampsia (p = 0.028; median = 2233 pg/mL vs. controls, median = 1644 pg/mL), or delivered a small-for-gestational-age infant (p = 0.002; median = 2109 pg/mL vs. controls, median = 1614 pg/mL). SPINT2 was elevated in the placentas of patients who required delivery for preterm preeclampsia (p = 0.025). Though inflammatory cytokines had no effect, hypoxia increased SPINT2 in cytotrophoblast stem cells, and its expression was elevated in the placental labyrinth of growth-restricted rats. These findings suggest elevated SPINT2 is associated with placental insufficiency. MDPI 2021-07-12 /pmc/articles/PMC8305184/ /pubmed/34299087 http://dx.doi.org/10.3390/ijms22147467 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Murphy, Ciara N.
Walker, Susan P.
MacDonald, Teresa M.
Keenan, Emerson
Hannan, Natalie J.
Wlodek, Mary E.
Myers, Jenny
Briffa, Jessica F.
Romano, Tania
Roddy Mitchell, Alexandra
Whigham, Carole-Anne
Cannon, Ping
Nguyen, Tuong-Vi
Kandel, Manju
Pritchard, Natasha
Tong, Stephen
Kaitu’u-Lino, Tu’uhevaha J.
Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction
title Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction
title_full Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction
title_fullStr Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction
title_full_unstemmed Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction
title_short Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction
title_sort elevated circulating and placental spint2 is associated with placental dysfunction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305184/
https://www.ncbi.nlm.nih.gov/pubmed/34299087
http://dx.doi.org/10.3390/ijms22147467
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