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The Laboratory of Environmental Health, Reproduction, and Development

Department of Epidemiology

University of Pittsburgh Graduate School of Public Health

PI: Dr. Jennifer J. Adibi ScD, MPH

Environmental, reproductive, and molecular epidemiology


Research Overview

Human fetuses undergo development while suspended in fluids that contain a complex mixture of environmental chemicals. This includes synthetic compounds prevalent in modern day foods, food packaging, personal care products, the indoor environment, air, and water. Even though most babies are born healthy and without birth defects; these exposures can cause changes at a molecular level.

Are these changes measurable and reproducible in human populations? Are they meaningful with respect to the exposure and the long-term health of the child and the mother? The work of our laboratory is to measure these molecular changes and understand their significance to the health of the future child.

This process is referred to as endocrine disruption, the theory that synthetic chemicals in our environment can cause chronic disease by mimicking biologic molecules in our bodies. This can occur during key transitions over the lifespan (fetal development, puberty, reproduction, menopause). Mimicry in this case refers to disruption in epigenetic regulation, and/or gene and protein expression. Some chronic health disorders studied as consequences of endocrine disruption are infertility, obesity, diabetes, asthma, and neurobehavioral disorders.

Because the fetus cannot be sampled or observed directly, we do this by measuring the response of the placenta. The placenta is a fetal endocrine organ that serves as a physical, physiologic and statistical mediator of maternal exposures. It produces molecules in abundance that can be sampled at key developmental timepoints in maternal blood, urine, cord blood, and placental tissue. With careful selection of biomarkers, we can simultaneously measure a placental response to an exposure and early indication of risk of a future outcome in the child.

Currently our laboratory is funded by the National Institute of Environmental Health Sciences (NIEHS) to pursue an interdisciplinary approach to the above questions that includes 1) placental tissue analysis of phthalates, mRNAs, and proteins; 2) in vitro culture of first trimester human placentas and fetal gonads to evaluate phthalate effects on both organs; 3) causal mediation analysis in birth cohorts to evaluate the placenta as a mediator of the association between phthalates and anogenital distance.

Areas in which we have worked and are currently working:

  1. Bringing the placenta into the epidemiology of endocrine disruption. Starting in 2010, we have studied the human placenta as a novel approach to quantify the effects of phthalates in pregnancy.
  2. Discovery of phthalate effects on a placental hormone called human chorionic gonadotropin (hCG). We measured an association of maternal urinary phthalates and placental mRNAs that encode proteins in the hCG pathway. We have since confirmed this finding experimentally using in vitro models of primary human placental tissue, by measuring the hCG protein, and have replicated this finding in three independent birth cohorts. hCG is a human and placenta specific (some expression in cancers and other endocrine organs) hormone which is essential to pregnancy maintenance and fetal development. We theorize that it may also be important in the programming of maternal post-partum health.
  3. Establishing phthalate effects via the placental transcriptome. Using placental tissue collected in the first trimester and the third trimester, we have measured the placental transcriptome (a quantitative measure of the expression of all genes expressed in a sample, in the ballpark of 20,000 genes) to confirm the above-described association with hCG, and to gain insight into the molecular gene expression signature that can help to explain this association.
  4. Applying causal mediation and other analytical strategies to quantify placental mediation of exposure effects on fetal development and maternal health. Within our research group, we are applying methods in causal mediation to our research questions. This is one strategy to quantitatively incorporate information on the placenta. We have developed a statistical method and R package to identify shapes of association between continuous biomarkers and outcomes when the linear model is potentially insufficient or incorrect. We have extended this approach to causal mediation in cases where the mediator-outcome association is not linear.
  5. Theory building in placental-fetal endocrine disruption. We are developing, in a review paper and empirically, a critical theory specifically on molecular pathways in the placenta that are sources of biomarkers in the first trimester and which can be useful to more accurately establish associations between environmental exposures in pregnancy and outcomes.
  6. Plugging the placenta into a health equity lens on race disparity in pregnancy. Pittsburgh suffers from one of the starkest disparities in the U.S. between Black and White women in risk of adverse pregnancy outcome (preterm birth, infant mortality, maternal mortality). We are pursuing placental biomarker-based strategies to evaluate early points at which these differences may first be measurable in pregnancy. The aim is to identify structural and individual level causes of discrimination, their relationship to specific exposures in pregnancy and their physiologic effects in pregnancy. This work may lead to opportunity for intervention. Our research goal is to create a pathway to equitable approaches to healthy pregnancy. 


Adibi Laboratory

130 Desoto Street, 5132 Public Health
Pittsburgh, PA 15261
adibij@pitt.edu
412-624-1913