About

Rebecca A. Simmons, M.D., holds the position of Hallam Hurt Professor in Neonatology at the University of Pennsylvania School of Medicine. She is also the Associate Director of the Center for Research, Reproduction and Women's Health, and the Director of the Career Development Core for the Center of Excellence in Environmental Toxicology (CEET). Additionally, she serves as the Deputy Director of CEET and is a member of the Faculty Senate Executive Committee. Her research primarily focuses on elucidating the molecular mechanisms linking fetal growth retardation to the development of obesity and type 2 diabetes in adulthood. Her work involves studying oxidative stress, mitochondrial dysfunction, and epigenetic modifications in fetal and neonatal models, particularly in the context of intrauterine growth retardation (IUGR). She has developed rodent models to investigate how fetal growth restriction induces long-term metabolic disturbances, including insulin resistance and ß-cell dysfunction. Her research also explores therapeutic interventions, such as diet modifications, antioxidants, and neonatal administration of Exendin-4, which have shown promise in preventing diabetes and obesity in her models. Her work extends to understanding the effects of obesity during pregnancy on offspring, aiming to identify critical windows of susceptibility and molecular pathways involved in adipogenesis. Dr. Simmons's contributions are significant in advancing knowledge of fetal programming and metabolic disease prevention.

Research topics

• Biology
• Genetics
• Bioinformatics
• Obstetrics
• Medicine
• Mathematics
• Endocrinology
• Computational biology

Selected publications

• Exposure to a low dose mixture of endocrine disrupting chemicals alters the brain transcriptome and animal behavior

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-11

  articleOpen access

  Abstract Exposures to pervasive chemical toxicants such as endocrine disrupting chemicals (EDCs) are associated with adverse neurological and neurodevelopmental deficits. Although EDCs are widespread as sparse mixtures in the environment, most research has focused on single chemicals at high concentrations. Here, we studied the effects of ldEDC: a low-dose mixture of widely prevalent toxicants at doses representative of normal human exposure levels. Primary cultured mouse neurons treated with ldEDC exhibited altered gene expression compared to vehicle controls in genes critical for neuron activity, indicating low doses EDCs can affect neuronal function directly. We next tested persistent exposure through the maternal diet to define perinatal effects on offspring. Exposed offspring exhibited differences in development, tactile sensitivity, and sex-specific changes in motor behavior. Cortical single-nuclei sequencing identified broad transcriptomic changes, particularly in distinct cortical layer subpopulations, excitatory neurons, and astrocytes. Cell-cell signaling between neurons and non-neuronal populations were altered in exposed mice, specifically in pathways associated with cellular adhesion. Transcriptomic differences were also sex-specific. Together, these in vitro and in vivo findings reveal molecular and phenotypic consequences of EDC exposure at a mixture of doses well below commonly studied levels and highlights common functional pathways of susceptibility.

  PublisherOA PDFDOI

• Multi-omic profiling of early pregnancy small and large plasma extracellular vesicles reveals placental, metabolic, and structural adaptation signatures

  Zenodo (CERN European Organization for Nuclear Research) · 2026-12-31

  articleOpen accessSenior author

  Supplementary tables and figures supporting the manuscript: "Multi-omic profiling of early pregnancy small and large plasma extracellular vesicles reveals placental, metabolic, and structural adaptation signatures"

  PublisherDOI

• Multi-omic profiling of early pregnancy small and large plasma extracellular vesicles reveals placental, metabolic, and structural adaptation signatures

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-13

  articleOpen accessSenior authorCorresponding

  Early human pregnancy is a critical period characterized by rapid growth and extensive maternal-fetal communication that influence maternal and fetal outcomes. Circulating extracellular vesicles (EVs) have the capacity to capture cargo that reflect these processes in real-time; however, signatures of EV subtypes during early pregnancy are poorly defined. Here we quantified mitochondrial DNA (mtDNA) and performed transcriptomic and proteomic profiling of small (~100 nm) and large (~200 nm) plasma EVs from n=10 normal pregnancies (11-15 weeks) to define subtype-specific molecular signatures. mtDNA and mitochondrial protein content were more abundant in large EVs (lEVs). lEVs also contained a more complex set of long RNAs enriched for placental, immune, and mitochondrial-related transcripts compared with small EVs (sEVs). Proteomic profiling showed enrichment of canonical EV markers and extracellular matrix proteins in sEVs, whereas lEVs were preferentially associated with pregnancy-specific proteins, including proteins related to placental hormone production. MicroRNAs (miRNAs) accounted for ~25% of small RNAs in both EV subtypes with miR-223 and miR-16 enriched in lEVs and miR-639 enriched in sEVs. These data together, support a model where small and large plasma EVs have distinct, yet complementary signatures reporting systemic adaptations during the critical 11-15 week transition period. This work establishes a foundational framework for future studies linking EV signatures to placental dysfunction and adverse outcomes.

  PublisherOA PDFDOI

• Multi-omic profiling of early pregnancy small and large plasma extracellular vesicles reveals placental, metabolic, and structural adaptation signatures

  Zenodo (CERN European Organization for Nuclear Research) · 2026-12-31

  articleOpen accessSenior author

  Supplementary tables and figures supporting the manuscript: "Multi-omic profiling of early pregnancy small and large plasma extracellular vesicles reveals placental, metabolic, and structural adaptation signatures"

  PublisherDOI

• The Effect of Intrauterine Growth Restriction on the Developing Pancreatic Immune System

  Endocrinology · 2026-01-08

  articleOpen accessSenior author

  Immune cells in the pancreas are known to participate in organ development. However, the resident pancreatic immune system has yet to be fully defined. Immune cells also play a role in pathology and are implicated in diseases such as diabetes induced by intrauterine growth restriction (IUGR). We hypothesized that the resident immune system continues to develop during the neonatal period and is disrupted by IUGR. Using single-cell RNAseq and flow cytometry we identified many immune cell populations in the near-term fetus (at embryologic day 22) and neonatal (postnatal day 1, 7, &14) islets, non-endocrine pancreas, and the spleen in the rat. Using flow cytometry, we observed that the resident immune system dynamically changes during neonatal development in the pancreas and spleen. We identified 14 distinct immune populations in the pancreatic islets and 13 distinct immune populations in the spleen by single-cell RNAseq. There were no sex-specific differences in the relative proportion of immune cells in the pancreas or spleen. Finally, we tested if IUGR disrupted the neonatal immune system using bilateral uterine artery ligation. We found significant changes to the percentage of CD11B+ HIS48- and B cells in the islets and non-endocrine pancreas. IUGR-induced alterations were influenced by the tissue environment. Future research to define the role of these immune cells in pancreatic development may identify disrupted pathways that contribute to the development of diabetes following IUGR.

  PublisherOA PDFDOI

• Multi-omic profiling of early pregnancy small and large plasma extracellular vesicles reveals placental, metabolic, and structural adaptation signatures

  Zenodo (CERN European Organization for Nuclear Research) · 2026-12-31

  articleOpen accessSenior author

  Supplementary tables and figures supporting the manuscript: "Multi-omic profiling of early pregnancy small and large plasma extracellular vesicles reveals placental, metabolic, and structural adaptation signatures"

  PublisherDOI

• Maternal Exercise Rescues Fetal Akinesia‐Impaired Joint and Bone Development

  The FASEB Journal · 2025-12-13

  articleOpen access

  ABSTRACT Fetal movements exert mechanical forces that shape the developing skeleton. Conditions that impair fetal movement can cause skeletal defects, but interventions are limited. Here, we show that maternal wheel running exercise regulates fetal skeletal development in mice. In wild‐type fetuses, maternal exercise stimulated joint morphogenesis and bone development. These changes could not be fully explained by altered placental transport. Therefore, we next evaluated the effects of maternal exercise in the Splotch‐delayed (Sp d ) mouse model of fetal akinesia, which features intact maternofetal communication, but homozygous mutants lack contractile limb skeletal muscle. Maternal exercise substantially rescued fetal akinesia‐impaired joint and bone development and prevented disuse‐induced resorption of the deltoid tuberosity. Further, bioreactor mechanical stimulation of explanted Sp d limbs, which remove systemic factors, similarly stimulated joint morphogenesis. Together, these findings identify maternal exercise as a regulator of fetal skeletal development, provide a platform for studying skeletal developmental mechanobiology, and suggest potential therapeutic implications for maternal exercise in skeletal conditions caused by impaired fetal movement.

  PublisherOA PDFDOI

• Deciphering the Molecular Dialogue: Mitochondria, Epigenetics, and Extracellular Vesicles in Placental Function and Pregnancy Complications

  Comprehensive physiology · 2025-08-01 · 1 citations

  reviewOpen accessSenior author

  Placental dysfunction is implicated in the pathogenesis of multiple pregnancy complications. Mitochondria are the powerhouse of the cell and are critical for placental metabolism and function. Several pregnancy complications are associated with oxidative stress and mitochondrial alterations. Mitochondrial function is also essential for epigenetic modifications, which are pivotal in regulating gene expression during pregnancy. Extracellular vesicles (EVs) carry and transfer a variety of biological molecules, including intact mitochondria and mitochondrial components, and act as modifiers of epigenetics in recipient cells. Changes in the EV profile may serve as biomarkers for pregnancy complications. In the present review, we summarize the associations of mitochondrial dysfunction, epigenetic alterations, and changes in EVs that are associated with pregnancy complications. We also describe the link between mitochondria and epigenetics, mitochondria in EVs, and EVs in epigenetic modifications, which provide insight into the possible implications of crosstalk among mitochondria, epigenetics, and EVs in regulating placental function and adverse pregnancy outcomes.

  PublisherOA PDFDOI

• Gestational fine particulate matter exposures and spontaneous preterm birth: Elucidating mechanisms using placental transcriptome and metabolome signatures

  Placenta · 2025-09-22 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• Race and sex differences in placental lipid metabolism are associated with spontaneous early preterm birth

  Biology of Reproduction · 2025-04-17 · 5 citations

  articleSenior author

  Placental dysfunction is implicated in the pathogenesis of spontaneous preterm birth (SPTB). We investigated race (self-identified maternal race) and fetal sex differences in the placental metabolome and transcriptome associated with early SPTB (<32 weeks). Long-chain polyunsaturated fatty acids, acylcarnitines, acylglycerols, plasmalogens, and lysophospholipids were remarkably different between SPTB and Term placentas. These alterations were much more profound in Black than in White SPTB placentas. Mode of delivery and body mass index (BMI) had no effect on these differences. The lipid metabolic pathways disrupted in early SPTB placentas also exhibited fetal sex differences, particularly between Black male and Black female placentas. The expression of genes involved in multiple lipid metabolism regulating pathways (e.g., PI3K/AKT signaling and phospholipase activity), especially eicosanoid synthesis and secretion, was significantly altered in early SPTB placentas. The race- and sex-specific changes in lipid metabolites and gene expression were consistent with inflammation in SPTB placentas, which was further supported by dysregulation of various inflammation and immune response pathways. These findings reveal race and fetal sex differences in lipid metabolism and inflammation in SPTB placentas and suggest greater dysfunction and inflammation in Black compared to White SPTB placentas, which may explain mechanisms underlying early SPTB and the risk of SPTB in different populations.

  PublisherDOI

Recent grants

• Translational Research Training Program in Environmental Health Sciences

  NIH · $5.3M · 2012–2027

• NIH Grant R01ES023284

  NIH · $2.1M · 2018

• Environmental Health Informatics Core

  NIH · $16.5M · 2006–2030

• NIH Grant R01DK055704

  NIH · $3.6M · 2016

• NIH Grant K08DK002269

  NIH · $378k · 1999

Frequent coauthors

• Annette S. Flozak

  Northwestern University

  112 shared

• Yu‐Chin Lien

  University of Pennsylvania

  87 shared

• Robert H. Lane

  75 shared

• Edward S. Ogata

  60 shared

• Sara E. Pinney

  Children's Hospital of Philadelphia

  48 shared

• Amita Bansal

  Novartis (Switzerland)

  43 shared

• Gregory J. Reid

  30 shared

• Annette S Gounis

  Northwestern Memorial Hospital

  27 shared