The connection between a mother and her baby is profound. Beginning at the cellular level during pregnancy, the biological materials a mother exchanges with her child have a lasting impact on its development and well-being. In fact, recent research shows that these molecular exchanges are a key determinant of a person’s health over their lifetime.
New research from several Pew biomedical scholars is exploring the maternal-fetal connection to uncover the mechanisms behind this bond, and to learn how a mother’s health influences her child’s maturity and immunity. This work has the potential to offer insights on improving early diagnostic and preventive measures that can help ensure that children live long, healthy lives.
The earliest connection between a mother and child is made after a fertilized egg transforms into cells that form the embryo and the placenta, an organ that provides oxygen and nutrients from the mother to a growing fetus. To better understand how this process unfolds, Geetu Tuteja is studying the genetic networks that allow embryos to establish a healthy contact with the mother through the placenta. Using sequencing technologies and a novel tool for identifying enriched genes, her lab is investigating how placenta-forming cells are able to push into the maternal tissue—an important step that lays the groundwork for oxygen and nutrient exchange. Failures in this process can cause a number of disorders that may result in preterm births such as preeclampsia, which can dangerously raise the mother’s blood pressure, and intrauterine growth restriction, which results in a baby not growing at the expected rate. Therefore, developing targeted interventions that support a healthy connection are critical for promoting a healthy delivery.
Maternal antibodies, transferred to babies in utero and through breast milk, are essential for protecting infants from illness in their first few months of life. A discovery by Meghan Koch has newly shown that these antibodies also help promote an infant’s growth by establishing healthy bacteria in the gut. To further understand this process, Koch is evaluating how microbial species that help to regulate growth influence nutrient absorption and metabolism. Koch’s lab has previously found that a lack of maternal antibodies can lead to excessive immune activation in the gut, which can impair a baby’s weight gain even when it has adequate nutrition. Her team is also exploring how heightened immune responses cause long-term consequences for a baby’s metabolism and development, research that could inform new ways to treat infants experiencing insufficient growth—often called failure to thrive—and ensure that they reach their full developmental potential.
Lifestyle factors, such as smoking and stress, can negatively affect a developing fetus. However, the connection between infections during pregnancy and developmental delays or altered immune responses in infants has been more difficult to define.
Recent work by Tiffany Reese has shown that when pregnant mice are infected with intestinal worms, their offspring are more susceptible to the flu virus even into adulthood. This observation suggests that infection in the mother can influence the fetal immune system’s programming during development. Reese’s team is now investigating how immune cell makeup differs in mice born from mothers with or without an infection, and how this affects the offspring’s recovery from subsequent illnesses—research that could have implications for mothers who contract infections and their babies. Similarly, Anna Beaudin is exploring what happens to the infant’s developing immune system during maternal infection. After observing that infection can cause specific fetal stem cell populations—and the immune cells that they generate—to expand, her team is working to determine whether this expansion alters the immune function of mice offspring and makes them more susceptible to autoimmune disease.
Infection in mothers can also affect a child’s brain development. For instance, Jun Huh has observed that mice born from mothers that had infections exhibit anxiety and repetitive behaviors and avoid social engagement—actions that resemble some symptoms of autism spectrum disorders in humans. Subsequently, Huh’s lab has begun to investigate the effect that the maternal immune response has on the fetal brain. His team is looking specifically at how a molecule produced by Th17, a type of immune cell in the mother, crosses the placenta and alters brain development of the fetus. Huh’s work could offer new strategies to prevent neurodevelopmental disorders in infants.
Collectively, research from these promising investigators will enhance scientists’ understanding of the molecular connection between a mother and child as well as the remarkable impact this connection has for babies to reach their developmental potential.
Kara Coleman directs The Pew Charitable Trusts’ biomedical programs, including the biomedical scholars, Pew-Stewart Scholars for Cancer Research, and Latin American fellows programs, and Jennifer Villa is a principal associate supporting the programs.