# Environmental Exposures, AHR Activation, and Placental Origins of Development

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2021 · $521,580

## Abstract

PROJECT SUMMARY/ABSTRACT
Hemochorial placentation occurs in many mammalian species including primates and rodents. It ensures the
most intimate contact between maternal and embryonic compartments and requires specialized adjustments
during gestation. Disruptions in placental development and function affect fetal health and contribute to the
origins of adult disease. Our environment is a source of chemicals and toxicants that can affect cellular and
molecular processes, including those controlling the morphogenesis and function of the hemochorial placenta.
Timing of environmental exposures are likely critical in determining their effects on placentation and postnatal
health. Chemical properties of environmental exposures are wide-ranging and dictate cellular and molecular
responses. Polychlorinated biphenyls (PCBs) are released into the environment as a byproduct of industry
and when introduced prenatally have the capacity to influence embryonic and placental development. The aryl
hydrocarbon receptor (AHR) is a key component of a molecular pathway sensitive to a wide range of
xenobiotic exposures (including PCBs) and operative at the placentation site. AHR interacts with the AHR
nuclear translocator (ARNT) to regulate transcription of an expansive cadre of genes encoding enzymes,
transporters, etc. important in the biotransformation, metabolism, and detoxification of environmental
pollutants. Among the AHR target genes is cytochrome P450 1A1 (CYP1A1). CYP1A1 can catalyze the
biotransformation of both exogenous and endogenous substrates, which may contribute to the overall
mechanism of xenobiotic action on placenta development. The impact of environmental exposures on
placental development has received limited experimental attention. The foundation of our approach is that
there is conservation in the actions of environmental exposures on placentation. Our efforts in this research
proposal include complementary and interactive efforts with a relevant animal model, the rat, and with tissue
specimens from human pregnancies. We will apply our expertise in developmental biology, toxicology,
toxicogenomics, and perinatology to investigate the effects of environmental exposures on development of the
hemochorial placenta. Our focus is on a signaling pathway responsive to xenobiotic action (AHR) rather than
any one specific exposure. Aim No.1 utilizes rat models and trophoblast stem cells to investigate mechanisms
associated with xenobiotic activated AHR signaling on rat placental development and will be performed at the
University of Kansas Medical Center, Kansas City, whereas Aim No. 2 utilizes human placental tissue
specimens and pregnant human subjects to investigate mechanisms associated with xenobiotic activated AHR
signaling on human placental development and will be conducted at Children’s Mercy Kansas City.
Understanding molecular mechanisms critical for placental development in a “physiological context” is a key to
identifying relevant developmen...

## Key facts

- **NIH application ID:** 10176489
- **Project number:** 5R01ES029280-04
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Elin Grundberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $521,580
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176489

## Citation

> US National Institutes of Health, RePORTER application 10176489, Environmental Exposures, AHR Activation, and Placental Origins of Development (5R01ES029280-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10176489. Licensed CC0.

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