Pregnancy Health

Why Pregnancy?

The time period of fetal development is crucial for both maternal and long-term fetal health. During gestation, a developing infant is particularly vulnerable to environmental stress and complications that will impact health later in life. Many studies link the prenatal period with a wide array of long-term health outcomes that persist throughout life, ranging from mental health disorders to diabetes to increased risk of cardiovascular disease. Preterm birth is the leading cause of infant death worldwide, and the associated cost with care for preterm infants is $26.2 billion per year in the U.S. alone. Additionally, maternal complications during pregnancy affect maternal health later in life. For example, women who experience preeclampsia during pregnancy are at double the risk of heart disease or stroke later in life. Altogether, pregnancy complications put a burden on caregivers, families, and the health care system.

What is ISB doing?

ISB researchers, along with our external collaborators, are using systems biology to map molecular network dynamics in normal pregnancy, as well as study changes that occur in pregnancies with complications such as preterm birth. By using a systems approach, we hope to gain a more comprehensive understanding of pathological changes that occur in pregnancy, and identify women most at risk of developing pregnancy complications such as preterm birth.

To date, our researchers have published on the following topics:

  • Using integrated genomic, epigenomic and transcriptomic data from mothers, fathers and infants, we have identified genomic variants associated with PTB and identified 72 candidate biomarker genes for very early preterm birth.
  • We have identified transcriptomic changes in placentas from babies who have been born prematurely compared to normal term deliveries by mining publicly available datasets
  • We have performed comprehensive characterization of microRNAs, mRNAs and proteins in blood of women who have undergone spontaneous preterm labor. Our work has revealed immune signaling changes related to premature labor. This work has been released as a series of three independent manuscripts.
  • We have unveiled patterns in expression of miRNAs which are produced in the placenta and circulate to the mother and baby.
  • We have characterized how changes in expression of metabolic genes in different maternal organs change across pregnancy using mouse models.

Funding & Ongoing Research

Our ongoing work has been supported by the following research grants.

Systems Biology Approaches to Birth Timing and Preterm Birth Risk
The major goal of this project is to test the hypothesis that the convergence of functional data from gene expression and proteomic studies with existing GWAS and exome sequencing investigation will reveal critical targets for preterm birth risk that are not obvious from analysis of the individual datasets in isolation.
Gates Foundation
OPP1113966
11/17/14–10/31/18
PI: Nathan Price (ISB) and Louis Muglia (Cincinnati Children’s Hospital)

Harnessing “omics”: A Systems Biology approach to discovery of biological pathways in placental development and parturition
We will seek to identify key genes and pathways associated with placental maturity that are quantifiable in maternal serum and urine, as well as to create a transcriptional regulatory network in the placenta using Transcriptional Regulatory Network Analysis (TRENA), which has been developed by the Price lab as part of the NIH Accelerating Medicines Program and a Big Data to Knowledge
NIH R01 HD091527
03/10/17 -02/28/22
PI: Nathan Price (ISB) and Louis Muglia (Cincinnati Children’s Hospital)

The role of Corticoptrophin Releasing Hormone on Placental Transcriptional Networks and Birth Timing.
This proposal seeks to determine the molecular mechanisms linking corticotrophin releasing hormone (CRH) to gestational length using transcriptional regulatory network analysis. This study will enhance our knowledge of the role of CRH in orchestrating parturition and identify transcriptional drivers that dictate gestational length, which may provide clinical biomarkers for early identification and treatment of spontaneous preterm labor.
NIH/NICHD K99HD096112
08/01/2018-08/1/2020
PI: Alison Paquette (ISB)

Leveraging Transcriptional Regulatory Networks for Exposure Analysis.
The objective of this Opportunities and Infrastructure proposal is to construct and distribute an innovative, genome scale placental specific transcriptional regulatory network (TRN). We will make this TRN accessible through ECHOPortal, allowing investigators to identify transcriptional regulation in the placenta that is integral to child health and development. We will use this network to uncover changes in transcriptional regulation related to phthalate exposure using the ECHO PATHWAYS cohorts.
ECHO Opportunities and Infrastructure Grant
09/01/2019-09/1/2021
PI: Alison Paquette (ISB)

Publications

  • Fallen, S., Baxter, D., Wu, X., Kim, T.-K., Shynlova, O., Lee, M.Y., Scherler, K., Lye, S., Hood, L., Wang, K., 2018. Extracellular vesicle RNAs reflect placenta dysfunction and are a biomarker source for preterm labour. J. Cell. Mol. Med. https://doi.org/10.1111/jcmm.13570
  • Knijnenburg, T.A., Vockley, J.G., Chambwe, N., Gibbs, D.L., Humphries, C., Huddleston, K.C., Klein, E., Kothiyal, P., Tasseff, R., Dhankani, V., Bodian, D.L., Wong, W.S.W., Glusman, G., Mauldin, D.E., Miller, M., Slagel, J., Elasady, S., Roach, J.C., Kramer, R., Leinonen, K., Linthorst, J., Baveja, R., Baker, R., Solomon, B.D., Eley, G., Iyer, R.K., Maxwell, G.L., Bernard, B., Shmulevich, I., Hood, L., Niederhuber, J.E., 2019. Genomic and molecular characterization of preterm birth. Proc. Natl. Acad. Sci. 116, 5819. https://doi.org/10.1073/pnas.1716314116
  • Paquette, A., Baloni, P., Holloman, A.B., Nigam, S., Bammler, T., Mao, Q., Price, N.D. Temporal transcriptomic analysis of metabolic genes in maternal organs and placenta during murine pregnancy. Biol. Reprod, 2018. https://doi.org/10.1093/biolre/ioy148
  • Paquette, A., Chu, Tianjiao, Wu, Xiaogang, Wang, Kai, Price, Nathan, Sadovsky, YoelDistinct communication patterns of trophoblastic miRNA among the maternal-placental-fetal compartments. Placenta, 2018. https://doi.org/10.1016/j.placenta.2018.10.004
  • Paquette, A.G., Brockway, H.M., Price, N.D., Muglia, L.J. Comparative transcriptomic analysis of human placentae at term and preterm delivery. 2018, Biol. Reprod.. https://doi.org/10.1093/biolre/iox163
  • Paquette, A.G., Shynlova, O., Kibschull, M., Price, N.D., Lye, S.J.. Comparative analysis of gene expression in maternal peripheral blood and monocytes during spontaneous preterm labor. Am. J. Obstet. Gynecol, 2018. https://doi.org/10.1016/j.ajog.2017.12.234
  • Paquette AG, Shynlova O, Wu X, PhD, Kibschull M, Wang K, Price ND, Lye SJ . MicroRNA-transcriptome networks in whole blood and monocytes of women undergoing preterm labor. Journal of Cellular and Molecular Medicine DOI: https://doi.org/10.1111/jcmm.14567