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Article

Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction

1
The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, Australia
2
Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia
3
The Department of Anatomy and Physiology, The University of Melbourne, VIC 3010, Australia
4
Manchester Academic Health Science Centre, St Mary’s Hospital, University of Manchester, Manchester M13 OJH, UK
5
The Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, VIC 3086, Australia
*
Author to whom correspondence should be addressed.
Equal contribution.
Academic Editors: Hiten D. Mistry and Eun Lee
Int. J. Mol. Sci. 2021, 22(14), 7467; https://doi.org/10.3390/ijms22147467
Received: 21 June 2021 / Revised: 8 July 2021 / Accepted: 8 July 2021 / Published: 12 July 2021
(This article belongs to the Special Issue Placental Related Disorders of Pregnancy)
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. View Full-Text
Keywords: placental insufficiency; SPINT2/HAI-2; preeclampsia; foetal growth restriction; intrauterine growth restriction; small for gestational age placental insufficiency; SPINT2/HAI-2; preeclampsia; foetal growth restriction; intrauterine growth restriction; small for gestational age
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MDPI and ACS Style

Murphy, C.N.; Walker, S.P.; MacDonald, T.M.; Keenan, E.; Hannan, N.J.; Wlodek, M.E.; Myers, J.; Briffa, J.F.; Romano, T.; Roddy Mitchell, A.; Whigham, C.-A.; Cannon, P.; Nguyen, T.-V.; Kandel, M.; Pritchard, N.; Tong, S.; Kaitu’u-Lino, T.J. Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction. Int. J. Mol. Sci. 2021, 22, 7467. https://doi.org/10.3390/ijms22147467

AMA Style

Murphy CN, Walker SP, MacDonald TM, Keenan E, Hannan NJ, Wlodek ME, Myers J, Briffa JF, Romano T, Roddy Mitchell A, Whigham C-A, Cannon P, Nguyen T-V, Kandel M, Pritchard N, Tong S, Kaitu’u-Lino TJ. Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction. International Journal of Molecular Sciences. 2021; 22(14):7467. https://doi.org/10.3390/ijms22147467

Chicago/Turabian Style

Murphy, Ciara N., Susan P. Walker, Teresa M. MacDonald, Emerson Keenan, Natalie J. Hannan, Mary E. Wlodek, Jenny Myers, Jessica F. Briffa, Tania Romano, Alexandra Roddy Mitchell, Carole-Anne Whigham, Ping Cannon, Tuong-Vi Nguyen, Manju Kandel, Natasha Pritchard, Stephen Tong, and Tu’uhevaha J. Kaitu’u-Lino 2021. "Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction" International Journal of Molecular Sciences 22, no. 14: 7467. https://doi.org/10.3390/ijms22147467

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