Placental mRNA and Protein Expression of VDR, CYP27B1 and CYP2R1 Genes Related to Vitamin D Metabolism in Preeclamptic Women

(1) Background: Considerable evidence indicates that the occurrence of preeclampsia (PE) is associated with a reduced vitamin D (VD) level. Several studies have found that VD deficiency is correlated with disturbed trophoblast invasion, reduced angiogenesis and increased vasoconstriction. Because the vitamin D receptor (VDR) and CYP27B1 and CYP2R1 hydrolases are strongly involved in VD metabolism, the goal of the present study was to evaluate their genes and proteins expression in the placentas from preeclamptic women. (2) Methods: Samples and clinical data were obtained from 100 Polish women (41 women with preeclampsia and 59 healthy pregnant controls). The whole PE group was divided into subgroups according to gestation week of pregnancy ending before and after 34 gestational weeks (early/late-onset preeclampsia (EOPE/LOPE)). However, finally, to reduce confounding by differences in gestational age, the EOPE group was excluded from the analysis of mRNA and protein placental expression, and we focus on the comparison between LOPE and control groups. The placental VDR, CYP27B1 and CYP2R1 mRNA expression was analyzed using RT-PCR, and placental protein levels were determined by ELISA assay. (3) Results. (3.1) Placental gene expression: Expression levels of both genes, CYP27B1 (1.17 vs. 1.05 in controls, p = 0.006) and CYP2R1 (2.01 vs. 1.89 in controls, p = 0.039), were significantly higher in preeclamptic placentas than in the control group. Interestingly, VDR expression was significantly lower in placentas from the PE group (1.15 vs. 1.20 in controls, p = 0.030). After dividing all preeclamptic women into subgroups only for the CYP27B1 gene, a significantly higher placental expression in the LOPE subgroup than the healthy controls was observed (padj = 0.038). (3.2) Placental protein expression: The results revealed that protein expression levels of CYP27B1 in the preeclamptic group were similar (5.32 vs. 5.23 in controls, p = 0.530). There was a significant difference in median VDR and CYP2R1 protein levels between studied groups (VDR: 2.56 vs. 3.32 in controls, p < 0.001; CYP2R1: 1.32 vs. 1.43 in controls, p = 0.019). After stratification of preeclamptic women into subgroups, a significant difference was observed only in the VDR protein level. The medians in the LOPE subgroups were significantly lower compared to the healthy control group. In the whole study group, the placental VDR protein level was inversely correlated with systolic and diastolic blood pressure (all p < 0.001), and positively correlated with gestational age (p < 0.001) and infant birth weight (p = 0.014). (4) Conclusions: Lower mRNA and protein expression of VDR in preeclamptic placentas, and also VDR protein expression, could play a pivotal role in preeclampsia development. Additionally, the higher mRNA expression of both CYP27B1 and CYP2R1 hydrolase genes in placentas from preeclamptic women could indicate the compensatory role of these enzymes in preeclampsia etiology. Our results also indicate that placental VDR protein level could be one of the factors modulating blood pressure in pregnant women, as well as influencing gestational age and infant birth weight. Considering the importance of these findings, future studies are warranted.

Predictive Performance of Placental Protein 13 for Screening Preeclampsia in the First Trimester: A Systematic Review and Meta-Analysis

Preeclampsia is a pregnancy-specific syndrome that affects maternal and neonatal mortality. Several serum biomarkers can be used to predict preeclampsia. Among these proteins, placental protein 13 (PP13) has received progressively more interest in recent studies. The decrease in PP13 expression is one of the earliest signs for the development of preeclampsia and has shown its predictive performance for preeclampsia. In this meta-analysis, we collected 17 observational studies with 40,474 pregnant women. The overall sensitivity of PP13 to predict preeclampsia was 0.62 [95% confidence interval (CI) = 0.49–0.74], the specificity was 0.84 (95%CI = 0.81–0.86), and the diagnostic odds ratio was nine (95%CI = 5–15). The area under the curve for summary receiver operating characteristic was 0.84. We then chose the early-onset preeclampsia as a subgroup. The sensitivity of early-onset subgroup was 0.63 (95%CI = 0.58–0.76), the specificity was 0.85 (95%CI = 0.82–0.88), and the diagnostic odds ratio was 10 (95%CI = 6–18). The findings of our meta-analysis indicate that PP13 may be an effective serum biomarker for the predictive screening of preeclampsia. Nonetheless, large prospective cohort studies and randomized controlled trials are expected to uncover its application in clinical practice. The heterogeneity of the original trials may limit the clinical application of PP13.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=188948 The meta-analysis was registered in PROSPERO (CRD42020188948).

Role of Maternal Serum Placental Protein 13 at 11-13 weeks of Pregnancy as a Predictor of Pre-eclampsia

Background: Prediction of pre-eclampsia is very important during pregnancy. Objective: The purpose of the present study was to find out the role of maternal serum placental protein 13 at 11 to 13 weeks of pregnancy as a predictor of pre-eclampsia. Methodology: This prospective cohort study was carried out including 83 pregnant women with early gestation (11-13 weeks) attending the antenatal clinic of BSMMU hospital, Dhaka, during the period of July 2019 to December 2019 for a period of six months. Maternal serum was taken for measurement of Placental Protein 13 by ELISA technique. Then the subjects were regularly followed up to term. At each visit they were clinically evaluated by measuring blood pressure and testing urine for protein by heat coagulation method. Proteinuria was confirmed by measuring 24 hour urinary total protein. Result: Out of 83 cases, 5 developed preeclampsia. The mean value of Placental Protein 13 in non-preeclampsia patients was 167.5±8.79 and in pre-eclamptic patients was 131.54±20.06. The cutoff point value of Placental Protein 13 for prediction of preeclampsia was 0.68 MoM. Area under curve (AUC) was 0.93. Sensitivity, specificity, positive predictive value and negative predictive value of this test were 80.00%, 94.94%, 50.00% and 98.68% respectively. The accuracy of this test was 93.98%. Conclusion: In conclusion maternal serum Placental Protein 13 can predict risk of development of preeclampsia. Journal of National Institute of Neurosciences Bangladesh, January 2021, Vol. 7, No. 1, pp. 47-51

The association between urinary placental protein 13 and soluble fms- like tyrosine kinase-1 in preeclamptic women in the third trimester of pregnancy

Background: Preeclampsia (PE) is diagnosed after 20 weeks of gestation. This multisystem disorder affects 2-7% of pregnant women. Preeclampsia (PE) is a serious complication of pregnancy and one of the main causes of maternal and neonatal mortality and morbidity in the world. The inadequate placentation process results in a change in anti-angiogenic factors levels, such as placental protein 13 and soluble fms-like tyrosine kinase 1 (sFlt-1). Objectives: To investigate the correlation between urinary placental protein (placental protein 13) and soluble fms like tyrosine kinase-1(sFLT-1) in preeclamptic women in their third trimester of pregnancy. Methods: A case-control study was carried out from August 2018 till January 2019. Urine samples were collected from pregnant women at Al-Elweyia Hospital, Al-Hakeem Hospital, and Al- Imamain alkadhimain Medical City. The patient groups include fifty women with preeclampsia in the third trimester (25 mild and 25 severe). Fifty healthy pregnant women (at their third trimester of pregnancy) were studied as a control group. Results: The mean urinary placental protein 13 levels were decreased in women with preeclampsia significantly (P? 0.05) (mild and severe) compared with healthy women (43.44± 4.914 pg/ml, 33.34± 1.863 pg/ml, and 51.84 ±2.60 pg/ml ) respectively. Also, urinary SFLT-1 concentrations were decreased non-significantly (P > 0.05) in women with preeclampsia (mild and severe) compared with healthy women (5.71±0.414 ng/ml, 5.31± 0.38 ng/ml and 6.01 ± 0.282 ng/ml) respectively. Conclusion: Urinary placental protein and soluble fms- like tyrosine kinase-1 levels in the third trimester of pregnancy were significantly correlated with the severity of preeclampsia, and urinary levels of placental protein 13 were found to be decreased significantly in patients with preeclampsia than in healthy pregnant women in the 3rd trimester of pregnancy.

Antiviral activity of a human placental protein of retroviral origin

SummaryViruses circulating in wild and domestic animals pose a constant threat to human health1. Identifying human genetic factors that protect against zoonotic infections is a health priority. The RD-114 and Type-D retrovirus (RDR) interference group includes infectious viruses that circulate in domestic cats and various Old World monkeys (OWM), and utilize ASCT2 as a common target cell receptor2. While human ASCT2 can mediate RDR infection in cell culture, it is unknown whether humans and other hominoids encode factors that restrict RDR infection in nature2,3. Here we test the hypothesis that Suppressyn, a truncated envelope protein that binds ASCT2 and is derived from a human endogenous retrovirus4,5, restricts RDR infection. Transcriptomics and regulatory genomics reveal that Suppressyn expression initiates in the preimplantation embryo. Loss and gain of function experiments in cell culture show Suppressyn expression is necessary and sufficient to restrict RDR infection. Evolutionary analyses show Suppressyn was acquired in the genome of a common ancestor of hominoids and OWMs, but preserved by natural selection only in hominoids. Restriction assays using modern primate orthologs and reconstructed ancestral genes indicate that Suppressyn antiviral activity has been conserved in hominoids, but lost in most OWM. Thus in humans and other hominoids, Suppressyn acts as a restriction factor against retroviruses with zoonotic capacity. Transcriptomics data predict that other virus-derived proteins with potential antiviral activity lay hidden in the human genome.