Gene Expression In Pup Placenta Tissue As A Result Of Maternal Immune Activation

Researcher(s)

  • Natalie Rivera, Neuroscience, University of Delaware

Faculty Mentor(s)

  • Elina Rodriguez, Psychological & Brain Sciences, University of Delaware
  • Mary Beth Bielicki-Hall, Psychological & Brain Sciences, University of Delaware
  • Jaclyn Schwarz, PhD, Psychological & Brain Sciences, University of Delaware

Abstract

 

Previous research has investigated the onset of developmental disorders such as autism, schizophrenia and various learning disabilities in offspring following immune activation during pregnancy. Maternal immune activation (MIA) has been shown to alter cognition as well as neural and glial expression in newborn offspring rat models, with symptoms being consistent with the aforementioned development disorders. Inflammatory immune responses in mothers are also thought to cause an influx of toxins and proteins in amniotic fluid, which could influence the development of their offspring. The goal of this project is to examine gene expression in fetal placenta tissue that is consistent with maternal immune activation. The immune molecules that we examined are standard inflammatory molecules that are upregulated following sickness or immune activation, which included Interleukin-1ꞵ (IL-1B), Interleukin-6 (IL-6), Toll-like receptor 4 (TLR4), Interleukin-10 (IL-10), Brain Derived Neurotrophic Factor (BDNF), Glial Cell Derived Neurotrophic Factor (GDNF), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Cell Death Inducing DFFA Like Effector B (CIDEB1),Netrin-G ligand-1 (NGL), and Ribosomal Protein Lateral Stalk Subunit P1 (RPLP1). Pregnant Sprague-Dawley female rats were injected with lipopolysaccharide (LPS; 50ug/ml/kg, i.p.) or saline on embryonic day 15 (E15). Lipopolysaccharide (LPS) is used to mimic immune response to bacterial exposure. Pup placenta samples were collected at 2, 4, or 24 hours post injection. Mothers were anesthetized with barbiturate euthanasia and perfused with 0.9% saline solution. Fetuses were collected prior to saline perfusion to avoid washing out immune factors in the amniotic fluid. Quantitative real-time polymerase chain reaction q(RT-PCR) was used to compare cytokine expression across the various conditions (LPS vs. Saline, extraction times, sex). Quantitative analysis was performed to understand cytokine-related gene expression using 18s, a relatively stable gene across treatment groups, as a reference gene.