Research Projects
Combining laboratory and field studies to identify molecular, cellular, and physiological changes associated with chemical exposures, with the goal of understanding how endocrine disrupting chemicals impact developmental and reproductive outcomes.
Impact of Endocrine Disrupting Chemicals (EDCs) on Implantation and the Placenta
Implantation is a complex process that requires coordinated signaling events to synchronize receptivity of the maternal uterine lining (endometrium) and blastocyst development.
Multiple signals are responsible for this synchronization, including peptide hormones, growth factors, cytokines, and immunological factors, majority of which are under the direction of the steroid hormones estrogen and progesterone.
The final step of implantation is trophoblast invasion of the maternal endometrium which initiates formation of the placenta, a transient maternal-fetal interface required for pregnancy maintenance and fetal development.
Because the events of implantation and placental development rely on hormone signaling, they are particularly susceptible to the effects of endocrine disrupting chemicals (EDCs), which interfere with hormone action in the body.
Currently, there are >1,000 man-made chemicals that have been identified as EDCs and numerous studies have highlighted these chemicals as reproductive toxicants.
Exposure to EDCs represents a significant risk factor for adverse outcomes on implantation, placentation, and pregnancy.
Model Organism
We will be using laboratory mice as our primary animal model because they share key structural similarities in reproductive tissues, like the placenta, and many of the same reproductive hormones as humans. Additionally, there is an abundance of molecular techniques that have been developed to work in mice.
Exposure Window
The preconception period is an under explored sensitive window of vulnerability to EDCs for cycling females, when steroid hormones are tightly regulated to promote dynamic remodeling of the endometrium which may contribute to adverse outcomes on implantation and placentation.
Endocrine Disrupting Chemicals
While there are many sources of EDCs this project will focus on chemicals found in products that are exclusively or predominantly used by women such as beauty and feminine hygiene products. Prevalent EDCs in these products include phthalates, parabens, bisphenols, and per- and polyfluoroalkyl substances (PFAS).
Techniques
We will utilize a combination of molecular and histological techniques to assess how EDC exposure impacts uterine receptivity, blastocyst priming, and placental development and function. Techniques will include scanning electron microscopy, immunohistochemistry, and single nucleus RNA-sequencing.
Consequences of Concurrent Endocrine Challenges on Maternal Health
(EDCs x Pregnancy)
During pregnancy there are significant hormonal, metabolic, and cardiovascular changes required to meet the needs of the growing fetus and uterus.
Maladaptation to the physiological demands of pregnancy can lead to pregnancy complications and predispose women to chronic conditions, such as type 2 diabetes, reproductive disorders, and cardiovascular disease.
Exposure to EDCs during pregnancy has been associated with increased risk of adverse health outcomes, including pregnancy complications, such as gestational hypertension, preeclampsia, gestational diabetes, ovulatory dysfunction, and cancer.
We still know very little about how these two endocrine stressors, pregnancy and exposure to EDCs, interact and contribute to maternal health outcomes, including subsequent pregnancies.
Interacting endocrine challenges resulting from pregnancy and exposure to EDCs represent significant risk factors for adverse maternal health outcomes.
Model Organism
We will be using laboratory mice as our primary animal model due to similarities with the human genome, hormone action, and pathophysiology of disease.
Exposure Window
Exposure will start on the day of conception and end on the day of birth, encompassing the entire duration of pregnancy. This will allow us to ask questions about how these co-occurring endocrine challenges impact pregnancy and maternal health after parturition.
Endocrine Disrupting Chemicals
Similar to project I, project II will focus on chemicals found in products that are exclusively or predominantly used by women such as beauty and feminine hygiene products.
Techniques
We will utilize a combination of molecular, histological, and physiological techniques to assess how EDC exposure and pregnancy impact maternal metabolism and reproductive potential. Techniques will include glucose and insulin tolerance tests, immunohistochemistry, radio immunoassays, and metabolomics.
Sentinel Animals as Bioindicators of Situational Environmental Exposures
Estuaries play an important role in marine ecosystems, providing a rich habitat for a variety of species to reproduce, feed, and grow.
Urbanization of the shores surrounding these coastal ecosystems has led to pollution by toxic chemicals which can accumulate in biota and threaten their health and survival.
In particular, upper trophic level predators may be especially vulnerable to the adverse impacts of contaminants that can bioaccumulate through the food chain and reach high concentrations in their blood and tissues.
Sharks play important ecological roles in marine communities as top predators, helping to balance populations of other organisms.
Because sharks utilize estuaries to varying degrees across age classes, with juveniles as long-term residents and adults being more transient, the role these coastal habitats play in bioaccumulation of contaminants is likely to differ across ontogeny.
Pollution of estuaries may threaten the health and survival of sharks based on degree of urbanization and across life stages.
Model Organisms
We will be sampling from broadnose sevengill (Notorynchus cepedianus) and tope (Galeorhinus galeus) sharks that utilize multiple estuaries along the west coast as pupping and nursery grounds.
Sample Collection
With the help of our marine biologist collaborators we will collect tissue samples (muscle and blood) from sharks as well as environmental samples (air, water, and sediment) in two different estuaries with varying degrees of urbanization.
Chemicals
We will measure concentrations of ubiquitous persistent contaminants, including organic contaminants, like per- and polyfluoroalkyl substances (PFAS), and heavy metals, such as mercury (Hg), in tissues and environmental samples.
Analysis Techniques
In situ concentrations of chemicals will be determined using high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) and thermal decomposition, amalgamation, atomic absorption spectrophotometry.
Funding
