Placental Telomere Attrition in Women with Preeclampsia

Abstract

Telomeres are tandem DNA repeats that cap the ends of linear chromosomes with repeats of the non-coding sequence TTAGGG. This DNA sequence along with specialized proteins prevents the uncapped DNA ends from triggering the DNA damage and senescence responses. Telomeres are crucial for maintaining eukaryotic genome stability through repression of DNA damage signalling. Telomeres shorten (telomere length attrition) with each cell division. Increased telomere attrition triggers DNA damage responses and cell cycle arrest. Telomere length plays a key role in placental development during pregnancy. Telomere attrition leading to shorter telomeres is suggested to be associated with pregnancy complications linked with abnormal placentation such as preeclampsia. Preeclampsia is a pregnancy specific disorder characterized by new onset hypertension after 20 weeks of gestation. It has a prevalence rate of 8-10% pregnancies in India. Abnormal placentation and placental insufficiency play central role in the pathophysiology of the disorder. Earlier reports on placental telomere length in pregnancy complications such as preeclampsia are inconclusive. It is suggested that nutrients such as fatty acids can influence telomere length. Evidence suggests that fatty acids are implicated throughout gestation for the growth and development of the placenta. Despite their importance, there are no reports on the association of maternal fatty acid status in early pregnancy with placental telomere length. Cross-sectional studies by us and others have reported altered fatty acid proportions and increased oxidative stress at delivery in pregnancies complicated with preeclampsia. There is a need to evaluate fatty acid levels and oxidative stress markers in early pregnancy with risk of preeclampsia. Further, the role of fatty acids and oxidative stress during pregnancy on placental telomere length has not been examined.