DNA Methylation In The Placenta: Accelerated Aging In Pregnancy Complications

Among the many organs, placenta is a very unique one as it is an extra-embryonic tissue. Placenta is mainly regulated by the fetal genome and is shared by the fetus and mother, as studied with the help of molecular biology products. However, since it is a transient organ that is only important in the pregnancy and gestation stage, it is extracted out and discarded after the baby is delivered. The main function of the placenta in pregnancy is yet to be completely discovered. Interestingly, this is one human organ that we know least about. Placenta comprises of very unique features along with its epigenetic mechanisms that regulate placental gene expression. This gene expression does not follow the same mechanisms and is not under the similar constraints as other organs. 

Recent studies and literature on DNA methylation in the placenta has highlighted the fact that this tissue gets very hypomethylated in the body as compared to other healthy tissues. That being said, scientists are yet to find the reasons of this relative DNA hypomethylation. Several studies have proven that DNA methylation inside the placenta increases across gestation. Additionally, DNA methylation patterns in the placenta are governed mostly partially methylated domains, and the genes in these domains are repressed. 

Some of the very complex and distinct attributes of placental DNA methylation profiles are most probably because of the different cell types that constitute this organ, along with the distinct epigenetic profiles of these cell populations. A renowned immunhiostochemical study proved that there are several differences in the amounts of 5-hydroxymethylcytosine, 5-methylcytosine, many histone modifications, and the DNA methyltransferase enzymes among the syncytiotrophoblasts and cytotrophoblasts. The former are derived with the help of fusion of the latter along with conduct transport, biosynthetic and endocrine functions of the placenta tissue. These help in development and working of maternal adaptations to pregnancy, nutrient delivery, and waste services to the fetus. 

The main objective of this research was to identify the dynamic alterations in epigenetic state in the placenta in the entire gestation. This is done to provide important understanding of usual placental development and working at the molecular level. It must be noted that this is significant in explaining what goes wrong in pregnancy complications. DNA methylation profiling mainly examined with the help of arrays, has helped find out DNA methylation alterations that are linked with pregnancy complications like preeclampsia, intrauterine growth restriction, preterm birth, and gestational diabetes. All of these pregnancy complications are attached with the life-long health problems and medical conditions for the baby and the mother, alike. However, in recent times, there has been a lot of research on this area and most of these studies have been done for pregnancy complications. In this study, meta-analysis is done by utilising the publicly available DNA methylation data for placenta. 

DNA methylation profiles of 387 different placental tissues were analysed. Researchers identified 741 CpG sites and 3 distinct methylated regions that heavily differed in placentas from normal and preeclamptic pregnancies. A comparison of uncomplicated pregnancies was done where 35 males and 27 female placentas were taken into account. 2898 were identified as differentially methylated CpG sites. Also, these were mostly on the X chromosome. 

The epigenetic clock was developed in 2013 by Mr. Horvath, who used Illumina DNA methylation arrays from 8000 samples having 51 healthy tissues. It was identified that 353 CpG sites were able to correctly predict age across several healthy tissues. After this work, epigenetic clock has been used in various datasets and the difference between predicted and actual age has been linked with medical conditions like infections, obesity, cancer, neurodevelopmental diseases and several others. DNA methylation in blood predicts mortality regardless of the illnesses and the way the particular person lives their life. This study used an almost same approach and identified 62 CpG sites that precisely predicted the gestational age of the placenta at sampling from 8-42 weeks’ gestation. The results showed that accelerated placental aging depended on early onset preeclampsia (less than 34 weeks’ gestation) but not late onset preeclamsia (the greater than or equal to 34 weeks’ gestation. (Bianco 2017)