Plasma level of hydroxysteroid (17-β) dehydrogenase 1 in the second trimester is an independent risk factor for predicting preeclampsia after adjusting for the effects of mean blood pressure, bilateral notching and plasma level of soluble fms-like tyrosine kinase 1/placental growth factor ratio

Abstract

Mean blood pressure (MBP), bilateral notching (BN) in the uterine artery and increased circulating levels of soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio are predictors of preeclampsia (PE). Recently, we disclosed that reducing the plasma level of hydroxysteroid (17-b) dehydrogenase 1 (HSD17B1), which is a steroidogenetic enzyme catalyzing the conversion of estrone to 17b-estradiol, is a potential prognostic factor for PE. Our aim was to evaluate whether HSD17B1 is an independent risk factor for predicting PE after adjusting for the effects of MBP, BN and the plasma level of the sFlt-1/PlGF ratio in the second trimester. One hundred and twenty-eight consecutive normal pregnant women without gestational hypertension (GH) or PE and 30 women with PE were selected from 1724 pregnant women. Multivariate logistic regression with a forward stepwise procedure was used to construct a prediction model. A past history of GH/PE, a family history of hypertension, pre-pregnancy body mass index, MBP, BN, plasma levels of sFlt-1/PlGF ratio and plasma levels of HSD17B1 were significantly associated with the occurrence of PE; however, only MBP (OR (95% confidence interval), 1.08 (1.03-1.14)), BN (7.5 (1.9-30)), sFlt-1/PlGF (21 (2.7-163)) and HSD17B1 (0.43 (0.22-0.85)) were independent risk factors for PE. The area under the receiver-operating-characteristic curve for the combination model was 0.89, yielding a sensitivity of 0.84, a specificity of 0.88 and a positive likelihood ratio of 7.2 (4.0-13). In conclusion, HSD17B1 is an independent risk factor for PE, and the combination of several risk factors including HSD17B1 in the second trimester may improve the prediction of PE.

Integrated Systems Biology Approach Identifies Novel Maternal and Placental Pathways of Preeclampsia

“…Predominantly placenta-expressed genes, down-regulated in module M1, are regulators of fetal growth ( CSH1, HSD11B2 ) ( 157 , 158 ), metabolism ( ESRRG ) ( 159 ), estrogen synthesis ( HSD17B1 ) ( 160 ), and immune functions ( LGALS14 ) ( 153 ), some of which were reported to be down-regulated in preeclampsia ( 30 , 91 , 130 , 155 , 161 , 162 ). Within this module, ESRRG, POU5F1 , and ZNF554 transcription regulatory genes had the highest number of significant correlations with predominantly placenta-expressed genes and, hence, deemed as hub factors (Figure S1 A in Supplementary Material).…”

Additive effects of mean blood pressure and bilateral notching in the second trimester on subsequent angiogenesis-related factors

“…It has been believed that the first stage is generated by the impairment of physiologic migration of trophoblasts into spiral arteries, a phenomenon that is reflected by abnormal UAD in the first and second trimesters, such as BN, high resistance index, high PI or high notch depth index. [4][5][6]17,18 However, it has been criticized because reduced perfusion, posited as secondary to failed remodeling of the maternal vessels supplying the intervillous space, is not sufficient to cause PE. 20,21 Maternal constitutional factors such as genetic susceptibility, obesity, diabetes and diet might be necessary to interact with reduced placental perfusion to lead to PE; 20,21 or oxidative stress, endoplasmic reticulum stress and inflammatory stress might be necessary to interact with reduced placental perfusion to lead to overt PE.…”

“…11 Abnormal increases in soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng), accompanied by the decrease of placental growth factor (PlGF), are also implicated in the generation of PE. [12][13][14][15][16][17] These increases are believed to be produced by placental hypoxia because of reduced perfusion, clinically represented as abnormal UAD. 14 We showed that HBP, BN, plasma levels of the sFlt-1/PlGF ratio and plasma levels of hydroxysteroid (17-b) dehydrogenase 1 in the second trimester were independent risk factors for PE; 17 and others also showed that HBP, high PI, decreased pregnancy-associated plasma protein-A and low PlGF levels in the first trimester were independent risk factors for not only early PE requiring delivery at o34 weeks but also late PE with delivery at X34 weeks.…”

Maternal urinary phthalates and sex-specific placental mRNA levels in an urban birth cohort

“…These placentas were sampled from the same pregnancies in which associations have been reported between prenatal phthalate concentrations and indicators of neurodevelopment at 3 and 7 years of age [23, 24]; with the risk of asthma at 8 years of age [25]; and the risk of obesity from 4 to 7 years [26, 27]. These candidate genes were chosen based on a priori knowledge of the transcriptional effects of phthalates, their expression in the human placenta (reviewed in [14]), and associations with placentally-mediated pathologies such as preeclampsia ( HSD17B1, CYP19A1, CGA, AHR ) [28–31], gestational diabetes ( PPARG, CGA ) [29, 32], fetal growth restriction ( AHR ) [28], and fetal programming ( SLC27A4 ) [33]. A secondary aim was to evaluate the independent relationships of the phthalates and placental biomarkers with these types of outcomes at birth (fetal size, gestational diabetes).…”