Their Impact OF Endocrine Disruptors On The Developing Fetus
Dr. Thomas Zoeller and colleagues researched how CYP1A1 expression correlated with the expression of genes regulated by thyroid hormone. Cytochrome P450 CYP1A1 is one of the pathways that processes many of the toxins present in our environment today, including PCB’s and tobacco smoke. Some of the metabolites produced in this process can impact thyroid function.
The test evaluated maternal and placental levels of thyroid hormone, mRNA levels of CYP1A1 and placental targets of thyroid hormone. In 32 out of the 164 placental samples, they found no CYP1A1 mRNA. Within this group, the cord blood thyroid hormone levels did correlate with placental expression of genes known to be regulated by TH. In the other 132 placental samples, where there were increased levels of CYP1A1 mRNA, with no correlation of thyroid hormone. There was a correlation between CYP1A1 mRNA and expression of TH-regulated genes. When there was evidence of activity of CYP1A1, there was no change in thyroid hormone levels, but there was a change in genes that TH regulates. So how did CYP1A1 affect gene expression without changing the levels of the intermediary TH?
These environmental chemicals can interfere with the action of thyroid hormone without actually changing thyroid hormone levels; instead they directly affect the thyroid receptor, and impact signaling to other genes via this mechanism. They also showed that in women who smoked during pregnancy, CYP1A1 mRNA levels were higher, and these CYP1A1 mRNAs cross the placenta and impact gene expression in the fetus.
As we know that genomic SNPs can impact CYP1A1 function, and can lead to altered levels of toxic metabolites, further questions to be answered from my perspective would be how do SNPs in this gene affect fetal exposure and future health during childhood and adulthood?
This is the second study I have come across recently that demonstrates that mRNAs can cross the placenta and impact fetal gene expression, and potentially have far-ranging effects on health. While the science continues to grow, we have enough information now to put into action. Personalized genomic medicine can be used to advise women on potential risks to their developing babies, and what they can do to reduce that risk.
For the original study article click here.