4.7 Article

Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction

期刊

出版社

MDPI
DOI: 10.3390/ijms22147467

关键词

placental insufficiency; SPINT2; HAI-2; preeclampsia; foetal growth restriction; intrauterine growth restriction; small for gestational age

资金

  1. National Health and Medical Research Council [1065854, 1183854, 116071, 2000732]
  2. National Health and Medical Research Council Fellowships [1159261, 1146128, 1136418]
  3. National Health and Medical Research Council of Australia [1183854, 2000732] Funding Source: NHMRC

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SPINT2 is identified as a potential biomarker for placental dysfunction, associated with preterm preeclampsia and intrauterine growth restriction.
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 (TNF alpha, 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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