The placenta is an essential organ in human development, and disruption of its function can result in problems in pregnancy including miscarriage, preterm labor, preeclampsia and intrauterine growth restriction. Additionally, disrupted placenta function during pregnancy has been associated with a great number of disorders and diseases that do not present until much later in the offspring's life such as metabolic syndrome, cardiovascular diseases, developmental delay and other neurodevelopmental and psychiatric disorders. How the exposures encountered in the environment drive alterations in placenta structure and function is poorly understood, and placenta function is difficult to assess in vivo using noninvasive methods. We propose to understand how gene expression is altered in the placenta during gestation by noninvasively characterizing the placenta transcriptome in association with exposure to chemicals known to alter endocrine signaling. These chemicals, called phthalates, are commonly found in a variety of commercial products such as plastics and personal care products, and phthalate exposure has also been shown to effect neurodevelopment. The link between phthalate exposure and placenta gene expression in vivo is not yet clear; therefore we have assembled a team comprised of neuroscientists, placenta biologists, environmental epidemiologists, and genomics experts do address how phthalate exposure and gestational age effects gene that are expressed in the placenta but not in other tissues. One of the advantages of the proposed research is that we will assess placenta gene expression noninvasively through RNA molecules contained in extracellular vesicles that are secreted into the urine of pregnant women. Collecting gene expression data and chemical exposure data from urine is highly clinically relevant, and we expect our approach will have clear translational applications just as home pregnancy tests that rely on the detection of placenta produced hormones in urine have become common. Our proposed study will provide the basic science background for the development of rapid, noninvasive tests for assessing placenta function, chemical exposures, and ultimately problems in neurodevelopment and other danger signals during pregnancy.
The proposed research will collect genome wide placenta gene expression data from 50 pregnant women at three time points during gestation. In addition to assessing gene expression differences the proposed research will develop methods to noninvasively determine placenta-originating transcripts among all transcripts existing in the urine of pregnant women. The proposed research will also compare gene expression to endocrine disrupting chemicals known to cause health problems.
| Armstrong, Don; Wildman, Derek E (2018) Extracellular Vesicles and the Promise of Continuous Liquid Biopsies. J Pathol Transl Med 52:1-8 |
