Summary: A new study focuses on the placenta’s role in transporting essential biological materials to the fetal brain.
The findings reveal that extracellular vesicles from the placenta play a crucial role in this process, potentially enabling earlier diagnosis of neurological disorders like ASD and schizophrenia.
This work has also shed light on how prenatal exposure to drugs and chemicals can affect long-term neurological and behavioral health.
Extracellular Vesicles as Transporters: Researchers discovered that microscopic vesicles from the placenta are key to delivering biological information to the developing fetal brain.
Potential for Early Disorder Diagnosis: This research could lead to early identification and potentially prevention of neurobehavioral diseases, changing the approach to prenatal care and interventions.
Impact of Prenatal Exposures: The studies have also highlighted how substances like opioids and BPA, when exposed to the fetus, can have long-term negative impacts on brain development and behavior.
Source: University of Missouri Columbia
For 30 years, Cheryl Rosenfeld has studied how biological information gets transferred from mothers to babies during pregnancy. The research is personal for Rosenfeld, whose niece, Sara, was exposed to sedative drugs in utero. Although the little girl was born healthy, she started developing respiratory, neurological, and other health issues in her teenage years.
“While I can’t reverse what was done to my niece, Sara, I can try to prevent similar things from happening to other children by learning more about how biological information gets transported during pregnancy,” said Rosenfeld, a professor of biomedical sciences at the University of Missouri College of Veterinary Medicine.
“The sooner we can identify abnormalities in fetal brain development, the sooner we can diagnose the potential for disorders to surface later in the baby’s life.”
The placenta, an organ that develops in the uterus during pregnancy, has a big job. It allows the fetus to communicate with its mother by transferring proteins, lipids, micro RNA and neurotransmitters to the fetal brain during pregnancy. For the first time — thanks to Rosenfeld’s recent study — researchers are learning exactly how that biological information is shuttled to the developing brain.
Rosenfeld found that microscopic extracellular vesicles — bubble-like microparticles produced by placental cells — act as a protective “shipping-and-handling” mechanism transporting important biological information from the placenta to emerging neurons.
The findings could lead to earlier diagnosis of neurological disorders including autism spectrum disorders (ASD) or schizophrenia.
“We’ve long known what information travels between the placenta and fetal brain, but we’ve never known how it gets there,” Rosenfeld said. “The extracellular vesicles are the missing link.” By sampling such structures either during pregnancy through the maternal blood or at birth via the placenta, it may lead to early diagnosis and ability to even prevent such neurobehavioral diseases.
Currently, individuals with neurological disorders may not get diagnosed until clinical signs and symptoms arise, (which might not be until the individual is a few years old). If disorders could be identified during pregnancy, interventions can begin much sooner, ultimately leading to improved long-term health outcomes.
A pioneer in her field
Rosenfeld’s research has also helped scientists and health care professionals better understand how medications or chemicals that are exposed to the fetus through pregnant mothers can potentially lead to long-term harm unintentionally.
For example, her 2022 study found prenatal opioid exposure may trigger neurological and behavioral changes later in life. Her 2021 study found that placentas exposed to bisphenol A (BPA) from the mother could negatively impact the fetal brain development of the offspring.
In 2021, Rosenfeld was named a Fellow of the American Association for the Advancement of Science (AAAS) in the Medical Sciences division for her efforts to advance biomedical sciences and her distinguished contributions to the field of reproductive biology.
Extracellular vesicles from mouse trophoblast cells: Effects on neural progenitor cells and potential participants in the placenta–brain axis
The fetal brain of the mouse is thought to be dependent upon the placenta as a source of serotonin (5-hydroxytryptamine; 5-HT) and other factors. How factors reach the developing brain remains uncertain but are postulated here to be part of the cargo carried by placental extracellular vesicles (EV).
We have analyzed the protein, catecholamine, and small RNA content of EV from mouse trophoblast stem cells (TSC) and TSC differentiated into parietal trophoblast giant cells (pTGC), potential primary purveyors of 5-HT. Current studies examined how exposure of mouse neural progenitor cells (NPC) to EV from either TSC or pTGC affect their transcriptome profiles.
The EV from trophoblast cells contained relatively high amounts of 5-HT, as well as dopamine and norepinephrine, but there were no significant differences between EV derived from pTGC and from TSC. Content of miRNA and small nucleolar (sno)RNA, however, did differ according to EV source, and snoRNA were upregulated in EV from pTGC.
The primary inferred targets of the microRNA (miRNA) from both pTGC and TSC were mRNA enriched in the fetal brain. NPC readily internalized EV, leading to changes in their transcriptome profiles.
Transcripts regulated were mainly ones enriched in neural tissues. The transcripts in EV-treated NPC that demonstrated a likely complementarity with miRNA in EV were mainly up- rather than downregulated, with functions linked to neuronal processes.
Our results are consistent with placenta-derived EV providing direct support for fetal brain development and being an integral part of the placenta–brain axis.