DERT Stories of Success
Martha Susiarjo, Ph.D.
NIEHS grantee Martha Susiarjo, Ph.D., studies how exposure to endocrine disrupting chemicals (EDCs) may negatively affect the health of a pregnant mother and her baby. EDCs are chemicals that can interfere with how hormones in the body communicate. Bisphenol A (BPA), flame retardants, and other contaminants that may act as EDCs are found in everyday consumer products, such as plastic bottles, metal food cans, and household furniture.
Although EDCs have been linked to adverse outcomes in pregnancy, there are still many unknowns. Susiarjo’s passion for this research stems from deep personal experiences. “My son was born prematurely, and I lost my childhood best friend due to pregnancy complications leading to eclampsia,” she said. “I want to understand what makes a healthy pregnancy and how different factors, including exposures, can negatively impact pregnancy outcomes.”
Pathway to an independent research career
As a graduate student at Case Western Reserve University, Susiarjo performed genetics research to determine the effects of BPA on oocyte development in mice. This research was conducted under the mentorship of Patricia Hunt, Ph.D., a geneticist who discovered chromosomal abnormalities in the offspring of pregnant mice inadvertently exposed to BPA from damaged caging materials.
After successful completion of her doctoral research in 2007, Susiarjo went on to receive postdoctoral training under the direction of Marisa Bartolomei, Ph.D., an epigenetics researcher at the University of Pennsylvania. While there, Susiarjo received an NIEHS postdoctoral training grant to study the impact of BPA exposure on the mouse epigenome.
“These experiences helped me get where I am today,” Susiarjo said. “I was very fortunate to have mentors who saw great potential in me and pushed me to do more.”
Susiarjo now leads research in her own laboratory at the University of Rochester School of Medicine and Dentistry. Her lab uses mice as a model organism to explore the molecular mechanisms that regulate the effects of EDCs on maternal health and fetal development during pregnancy. Her research shows that epigenetics, or heritable changes that affect gene expression without changing the genetic sequence in DNA, can play a large role in these effects.
Understanding mechanisms: Genomic imprinting and amino acid metabolism
One epigenetic phenomenon that Susiarjo studies is genomic imprinting, which is an important, natural process that causes one copy of a gene to be turned off, depending on whether it was inherited from the mother or father. DNA methylation is one well-characterized epigenetic mark that regulates the process of imprinting.
Research performed by Susiarjo and colleagues suggests that BPA exposure disrupts the process of genomic imprinting, which can negatively impact maternal health as well as fetal and placental development. In one study, they discovered that the embryos and placentas of BPA-exposed pregnant mice had significantly disrupted expression of imprinted genes. Furthermore, BPA-exposed offspring had significantly altered DNA methylation levels in imprinted genes such as insulin-like growth factor 2 (Igf2), a gene that plays a critical role in growth and development.
Since Igf2 also plays a role in diabetes and other metabolic disorders, Susiarjo and colleagues performed another study to investigate if BPA exposure in pregnant mice impacted metabolic health across multiple generations of their offspring. Results showed that gestational BPA exposure was associated with higher body fat and disrupted glucose homeostasis in first and second generation male offspring, and that these outcomes were linked to both fetal overexpression of the Igf2 gene and increased DNA methylation at the Igf2 locus.
Susiarjo and colleagues are also exploring novel molecular pathways that drive BPA-induced maternal and fetal metabolic disease. In a recent study, they determined that BPA-exposed pregnant mice and their fetuses had elevated levels of tryptophan, an essential amino acid. Previous studies have shown that tryptophan levels decrease during normal, healthy pregnancies and that this amino acid plays a role in maternal-fetal immune tolerance. Susiarjo and colleagues suspect the elevated tryptophan levels seen in the BPA-exposed mice could be associated with altered maternal-fetal immune tolerance, which is often linked to adverse pregnancy outcomes, such as miscarriages, preeclampsia, and gestational diabetes.
Susiarjo and her team are excited as they begin new studies to better understand the impact of EDCs on maternal-fetal immune tolerance during pregnancy.
“If you think about it, the developing fetus is really a foreign tissue in the mom,” said Susiarjo. “In some instances, the mom’s immune system may attack the fetus, leading to complications and potentially even fetal loss.”
Scientific literature shows that the Ido1 gene plays a key role in both placental tryptophan catabolism and maternal-fetal immune tolerance. Susiarjo and her team are working to explore the epigenetic regulation of the Ido1 gene in mice, and how gestational exposure to EDCs may lead to fetal loss and other adverse outcomes. The team is also exploring how vitamin B6 supplementation in mice can help prevent pregnancy complications, such as gestational diabetes.
“By understanding the environmental exposures and the molecular mechanisms involved, our research can inform preventive strategies for mothers to protect themselves and their babies during pregnancy,” said Susiarjo.