The Placenta, an Ephemeral Organ of Capital Importance

[This article was written by Mariona Bustamante , staff scientist at ISGlobal and Marta Cosín , post-doctoral researcher at ISGlobal].

The placenta —Latin for "flat cake”— is an organ found at the interface between the mother and the foetus, whose function is to support the development of the latter. In particular, it transports nutrients and oxygen from the mother and removes carbon dioxide and waste products, acts as a barrier to pathogens and chemical exposures, and produces hormones, immune factors and growth factors essential for maintaining pregnancy. It is also a highly adaptive organ: for example, when oxygen decreases in the maternal circulation, the number of capillaries in the placenta increases to ensure oxygen supply to the foetus.

There is growing evidence linking complications during pregnancy and thus placental functioning to foetal brain development and the risk of future psychiatric conditions

The placenta derives from the embryo and implants itself in the decidua, the outer lining of the maternal uterus, two weeks after conception. It is fully formed by 18-20 weeks, although it continues to grow throughout pregnancy. A poorly formed, implanted, or functioning placenta can compromise foetal growth. Conditions such as pre-eclampsia (characterised by high blood pressure and proteinuria in the mother and growth problems in the foetus), or prematurity (being born before 37 weeks of pregnancy) are some of the medical conditions in which the placenta has long been known to play an important role. However, there is growing evidence linking complications during pregnancy and thus placental functioning to foetal brain development and the risk of future psychiatric conditions, such as autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), or schizophrenia. There are several mechanisms by which the placenta affects the development of the foetal brain, but one of them is the synthesis of neurotransmitters and for this reason it is often referred to as the placenta-brain axis.

Previous studies have shown that maternal smoking during pregnancy produces epigenetic changes in inflammatory and placental growth factor signalling pathways and that these changes are associated with lower birth weight

The correct function of the placenta can be assessed by physiological measurements, for example by analysing the blood flow between the mother and the foetus using ultrasound, or by anatomical, histological or molecular measurements at the time of delivery. Molecular measures include the placental epigenome and transcriptome, which tell us which placental genes and biological pathways are or have been activated during pregnancy. This information allows us to establish "molecular bridges" between genetics, the adaptive responses of the placenta to environmental factors, and the placental dysfunction inherent to some pathologies. For example, previous studies have shown that maternal smoking during pregnancy produces epigenetic changes in inflammatory and placental growth factor signalling pathways and that these changes are associated with lower birth weight.

The Barcelona Life Study Cohort (BiSC), we collected a total of 600 placentas we measured DNA methylation levels and the profile of small non-coding RNAs (sncRNAs), two types of epigenetic markers

One of the goals in medicine is to develop markers that can predict the risk of suffering certain pathologies and, therefore, allow us to intervene before they develop. However, molecular markers in the placenta are too late to predict reproductive pathologies such as pre-eclampsia. It has been recently discovered that small RNAs produced by the placenta are released into the maternal circulation and can be detected in plasma or serum samples from mothers from the first trimester of pregnancy. Therefore, these types of markers hold great promise for developing screening strategies during the prenatal period.

This is why we put a lot ofeffort into collecting placentas in ISGlobal's new birth cohort studies, where we recruit mothers during pregnancy and follow their children into adolescence or beyond,. In fact, in the Barcelona Life Study Cohort (BiSC) , we collected a total of 600 placentas we measured DNA methylation levels and the profile of small non-coding RNAs (sncRNAs), two types of epigenetic markers. In addition, we have analysed telomere length, a marker of cellular ageing, and mitochondrial DNA content, a marker of oxidative stress. These data will allow us to unveil the biological mechanisms associated with air pollution, tobacco use or other exposures measured in BiSC. They will also allow us to investigate which placental pathways are affected in reproductive problems such as intrauterine growth restriction, or in later onset pathologies such as attention deficit hyperactivity disorder (ADHD), among others.

Recent studies have shown that activated carbon particles from air pollution as well as nanoplastics

Finally, as mentioned above, the placenta acts as a barrier to chemical compounds and pathogens. Recent studies have shown that activated carbon particles from air pollution as well as nanoplastics , microscopic fragments derived from plastics, can be detected in the placenta. Placentas collected in our studies will also be used to measure these exposures and investigate their possible health effects at birth and later in life, as current evidence is scarce.

Thus, the placenta is an ephemeral organ full of information not only about our embryonic and foetal past but also about our future health!