As part of the BiSC project, placenta samples have been collected on the day of birth. A total of more than 600 mothers’ placenta samples were collected!
Some of the main objectives of the collection of this type of sample are 1) to be able to characterize the molecular profiles of this tissue, 2) to study whether environmental factors such as exposure to air pollution during pregnancy have been able to alter these profiles, and 3) explore whether these alterations can affect the health of the newborn and later the child. To study these molecular profiles, we need to extract RNA and DNA from them. So far in the lab, we have been able to isolate the RNA and DNA of 360 mothers, and we continue! In addition, in a pilot study conducted last fall, we found that the quality of the RNA and DNA extracted was good enough to carry out the proposed studies.
In a previous post, we explained the importance of being able to analyze the placental epigenome, and in particular the DNA methylation patterns of this tissue. Today we want to talk about another epigenetic mechanism that we will study: MicroRNAs (remember that epigenetic mechanisms are those that regulate the expression of genes without modifying the DNA sequence).
MicroRNAs, as their name suggests, are a type of RNA. But first … what is RNA?
RNA or ribonucleic acid is the other type of nucleic acid that enables protein synthesis. While DNA contains genetic information (such as an instruction manual), RNA is what allows it to be understood by cells and executable. The most famous RNA is the messenger RNA, which is responsible for transmitting the coding information of DNA as a guideline for protein synthesis. However, this type of RNA represents a very small percentage of the total RNA that can be found in the cell (<3%). In contrast, non-coding RNA accounts for more than 80% of the total, and its function was previously unknown and was called “junk” RNA. Thanks to the work of many researchers, we now know that this RNA that does not encode proteins regulates biological processes such as gene expression, maintenance of DNA structure, inhibition of sex chromosomes, among others.
MicroRNAs are therefore a type of small, non-coding RNA (between 19 and 25 nucleotides) that regulate gene expression. They generally disrupt protein synthesis by interfering with intermediate steps (for example, preventing the acquisition of messenger RNA or promoting its degradation). These molecules can be modulated by environmental and genetic factors, and their alteration can also affect health and the risk of disease; for example, diabetes, muscular dystrophy, some allergies and cancers ….
In addition, recent findings suggest that placental microRNAs reflect intrauterine exposure and effects on various environmental factors, such as cigarette smoking and air pollution. In fact, it has also been hypothesized that placental microRNAs contribute to fetal neurological development, although much more research is needed.
A mass sequencing technique called RNA-seq is used to characterize microRNAs. In the case of BiSC, as we extract the RNA from the placenta samples and check their quality, it is taken to the Genomics Service of the Center for Genomic Regulation in Barcelona for sequencing. This center is located in the PRBB, where our laboratory is also located. So far we have sent 120 RNA samples, and before the end of the year a total of 400 will have been sent. Thus, during the first months of 2022 we will already have the sequencing data to quantify the different microRNAs in the placentas of BiSC and begin to study its profile, its modulation by environmental factors and its association with newborn characteristics such as neurodevelopment.
Finally, another very interesting aspect of these placental molecules that should be mentioned is that they are released into the maternal bloodstream throughout pregnancy and could therefore serve as biomarkers. Thus, by analyzing these and other biomarkers in maternal blood samples collected during pregnancy we could monitor placental function and detect possible risks to the fetus and the newborn or infant in order to act. prematurely (key in the prevention of diseases or clinical symptoms). As the BiSC research team is also interested in studying this great potential of microRNAs, we have applied for a scholarship to fund the study of microRNAs circulating in maternal blood during different periods of pregnancy. This project has been commissioned from the NIH (National Agency for Health Research of the United States) in collaboration with a research team from Columbia University. If the project is funded we will let you know right away! Let’s cross our fingers!
The text has been written by Marta Cosin, a researcher of the BiSC project.