Surfactant Protein (SP) induces preterm birth by promoting oxidative stress via upregulating Storkhead-Box Protein 1

Abstract Preterm birth is the leading cause of infant mortality. The mechanisms that instigate preterm birth remain elusive and this makes it difficult to predict or prevent preterm birth. In this study, the authors found that SP-A induced pathological damage to the placenta and promoted preterm birth. Through mechanism, SP-A promoted the expression of STOX1 which further promoted the oxidative stress in the placenta by inhibiting the activities of a series of antioxidant enzymes including SOD, CAT and GSH-Px. SP-A also induced dysregulation of arginine metabolism by inhibiting NOS2 and ARG2. Overexpression of STOX1 aggravated SP-A induced oxidative stress, pathological damage, and preterm birth, whereas knockdown of STOX1 alleviated SP-A induced oxidative stress, pathological damage and preterm birth. The present study uncovers that SP-A induces preterm birth by promoting oxidative stress via upregulating STOX1, which provides new targets for the prediction and prevention of preterm birth.

The Y153H Variant of the STOX1 Gene in Korean Patients with Preeclampsia

PURPOSE: Preeclampsia is a multifactorial disorder with genetic and environmental components. Recently, the STOX1 gene, identified as a candidate gene for preeclampsia in Dutch women, has been shown to be placentally expressed and subject to imprinting with preferential transmission of the maternal allele. The purpose of this study is to investigate whether there is an association between the STOX1 Y153H variation and preeclampsia in Korean pregnant women. MATERIALS AND METHODS: This study involved 202 preeclamptic and 204 healthy pregnant women who were genotyped for the Y153H variant of the STOX1 gene using a commercially available SNapShot assay kit and an ABI Prism 3730 DNA Analyzer. RESULTS: There were no significant differences in genotype frequencies of the Y153H variant of the STOX1 gene between preeclamptic patients and normal controls (P>0.05). The H allele frequency of the STOX1 Y153H variation was similar in patients with preeclampsia (87.1%) and in normal controls (86.5%). In addition, multiple logistic regression analysis showed that the YH, HH, and YH/HH genotypes were not associated with an increased risk of preeclampsia when compared to the YY genotype. CONCLUSION: This is the first study to characterize the Y153H variant of the STOX1 gene in Korean patients with preeclampsia. We found no differences in the genotype and allele frequencies between preeclamptic and normal pregnancies. Although limited by a relatively small sample size, our study suggests that the STOX1 Y153H variation is not associated with the development of preeclampsia in Korean pregnant women.