Quantitative Analysis of Placental Mitochondrial DNA in Severe Hypertensive Pregnancies: A Cross-sectional Study

Abstract

Introduction: To address the causes of maternal mortality and morbidity, reproductive health and related disabilities is a motto of World Health Organisation (WHO). Gestational hypertension constitutes as one of the main cause for maternal morbidity and mortality. Aetiology of gestational hypertension- remains a mystery. Mitochondrial dysfunction, particularly in trophoblastic cells, could play an important role in causing gestational hypertension and is postulated to be associated with oxidative stress, impaired differentiation and invasion of trophoblastic tissue. Alterations in peripheral blood mitochondrial Deoxyribonucleic Acid (DNA) copy numbers have been thought as a possible biomarker for mitochondrial dysfunction in disorders induced by oxidative stress. Aim: To estimate, evaluate and compare the mitochondrial copy numbers between placenta of severe gestational hypertensive pregnancies and normotensive pregnancies. Materials and Methods: A cross-sectional study was conducted at Tirunelveli Medical College Hospital, Tirunelveli, Tamil Nadu, India, with 25 clinically proven cases of severe gestational hypertensive pregnancies and 25 normotensive pregnancies, for a period of one year (August 2020 to July 2021). The placenta were collected from the Department of Obstetrics, in containers within two hours of delivery and frozen in liquid nitrogen. Relative quantitative analysis of placental mitochondrial DNA (mtDNA), were done by calculating the copy number value by comparing the levels of two nuclear genes viz., BECN1 and NEB to two mitochondrial genes viz., ND1 and ND6 by using real time quantitative Polymerase Chain Reaction (PCR). Results: The placental mitochondrial DNA copy number was higher in severe gestational hypertensive patients than in normotensive pregnancies. A total of 21 (84%) cases of the severe hypertensive placenta had higher copy numbers 100-110 vs only 13 (52%) cases had copy numbers 100-105 in the normotensive group. The difference in copy number value between them was statistically significant with p-value of 0.03. Conclusion: Present study findings suggest significant alterations at the level of the mitochondria in placenta from women with gestational hypertension, which may well contribute to gestational hypertension pathophysiology. Future research should include direct measure of placental and maternal whole body mitochondrial function, and assays that elucidate the potential modifiers of this association.

Keywords

• mitochondrial copy number
• normotensive
• severe gestational hypertension