Evaluation of MicroRNA-210 (miR-210) and Protein tyrosine phosphatase, non-receptor type 2 (PTPN2) in Pre-eclampsia

Abstract

Pre-eclampsia (PE) is a major cause of maternal and fetal morbidity or mortality, preterm birth, and intrauterine growth restriction. This disease is characterized by maternal high blood pressure and proteinuria after 20 weeks’ gestation. In serious cases, termination of pregnancy is the only available option to avoid health deterioration of the fetus and mother. Between 5% and 8% of pregnancies are affected by PE. It can reach up to 15% in Egypt. PE is responsible for about 70,000 maternal deaths and 500,000 infant deaths worldwide annually. The aim of this study is to assess the levels of expression of miR-210 and its target PTPN2 in Egyptian women with PE and compare them with normal pregnant women. This is in order to clarify their possible role in the progression and recurrence of PE and their relation to each other and to different clinicopathological factors. In the current study, the mean age of PE patients was (26.11± 6.47) years, while in healthy group it was (25.89± 4.63) years with no significant difference between the two groups (p>0.05). About preterm delivery, in PE group (20%) patients delivered preterm and (80%) delivered at term. All women in the control group delivered at term (100%) with high statistical significance (p≤0.01). As regards the birth weight in this study, mean birth weight was (2883.57 ± 336.12) g in PE group and it was (3100 ±343.64) g in the healthy group with significant difference (P<0.05). In the present study, the mean systolic blood pressure in PE group was 150.00 ±12.60 (140-190) mmHg and 113.71 ± 7.31 (100-120) mmHg in the healthy group with highly significant difference between the two groups (p<0.001). The mean diastolic blood pressure in PE group was 98.00 ± 10.52 (90-130) mmHg and in the healthy group was 74.57 ± 5.05 (70-80) mmHg with highly significant difference between the two groups (p<0.01). As regards the BMI in the present study, the PE group had (48.6%) overweight and (34.3%) obese and the control group had (40.0%) overweight and (22.9%) obese. The median BMI in Kg/m2 of PE group was 28 (23-34) Kg/m2 while in healthy group it was 27 (21-33) Kg/m2. The comparison was non significant between the two groups (p>0.05). As regards the placental weight in this study, mean placental weight was 384.69±53.29 (300-452g) in PE group and it was 452.66 ±15.32 (420-480g) in healthy group with highly significant difference (P<0.01). In this study, as regards the comparison between patients' blood pressure and different clinicopathological data in subjects of PE group, there was no significant difference between mild and severe HTN groups as regards age, gestational age, family history, type of delivery and BMI (p>0.05). But there was a highly significant difference between blood pressure and placental weight (p<0.01). Multiple pieces of evidence support the existence of hypoxia in PE. Endogenous miRNAs molecules are important mediators of numerous cellular processes, including the response to hypoxia. MiR-210, which is induced during hypoxia, is one of the most hypoxia sensitive miRNAs and is an ideal factor modulating the hypoxia response. MiR-210 mediates these functions by regulating a lot of target mRNAs. PTPN2 was one of miR-210 targets and was found to be down regulated by hypoxia. In the present study, the expression of miR-210 and its target PTPN2 were assessed in placental tissue samples from Egyptian women with severe and mild PE and from normal pregnant women in order to clarify a possible role of these genes in the progression of PE. In the study, there was a highly significant difference regarding the fold change of placental miR-210 among the three studied groups. The median placental miR-210 was 18, 23.31 and 0.54 in mild, severe and control groups respectively (P<0.0001).