Increasing evidence shows that a broad spectrum of both industrial and environmental chemicals can cause femaleovariantoxicity(ovotoxicity)andincreasetheriskofhormonalimbalance,ovarianfailure,andinfertility inbothhumansandothermammalianspecies.Theovaryistheprimaryfemalereproductiveorganandfunctions tosynthesizeandsecretsteroidhormonesandtosupporttheoocytematurationforovulation,fertilization,and pregnancy. Ovotoxicity can be measured in two ways, from the health of the developing ovarian follicle and gameteandfromtheabilityofthegonadstoproducehormones.Unfortunately,thelackofoptimalinvitromodels makes the current gold standard for testingthe ovotoxicity of chemicals rely on the use of laboratory animals. However,invivomodelsaretime-consuming,costly,andharmfultoanimals.Inourpreviousstudies,wehave used an alginate hydrogel-based encapsulation method to grow both mouse and human preantral follicles outside of the context of the ovary, which is termed encapsulated in vitro follicle growth (eIVFG). The eIVFG maintainsthe3Darchitectureofthefolliclesandsupportsfolliclegrowth,hormonesecretionaswellasoocyte maturationandovulation,suggestingapromisingmodelforinvitroovotoxicitytesting.However,thismethodis relativelyslow,andmultipleroundsoffollicleisolation,culture,andchemicalexposurearenecessarytocomplete dose-responseandtime-courseexperiments,makingthecurrenteIVFGscenarionotoptimal,particularlywhen arapidscreeningisrequiredinthecaseofunpredictableandemergingenvironmentalthreats.Inthisproposed project, we hypothesize that we can use cryopreservation technology and a confocal high-content imaging system to develop a high-throughput platform for screening ovotoxic chemicals.
In Aim 1, we will bank the isolatedovarianfolliclesthroughvitrificationforestablishingalong-termandready-to-usefolliclestorageplatform.
In Aim 2, we will use the ImageXpress confocal high-content imaging system to develop a high-throughput platformforfolliclemonitoring,assessing,andanalysis.Weexpectthattheseproposedstudieswillallowusto obtain rapid and reliable evidences to understand the impacts of environmental contaminants on the female reproductivesystem,toprovideguidancetoconductpreventiveandprotectiveactivities,aswellastominimize thedependenceanduseofanimals.

Public Health Relevance

The goal of this proposed study is to use cryopreservation technology and a confocal high-content imaging systemtodevelopahigh-throughputplatformforscreeningovariantoxicchemicals.Thesestudiesarecritically important to obtain rapid and reliable evidences to understand the impacts of environmental contaminants on thefemalereproductivesystem,toprovideguidancetoconductpreventiveandprotectiveactivities,aswellas tominimizethedependenceanduseofanimals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
1K01ES030014-01
Application #
9646864
Study Section
Special Emphasis Panel (ZES1)
Program Officer
Schug, Thaddeus
Project Start
2018-12-15
Project End
2021-11-30
Budget Start
2018-12-15
Budget End
2019-11-30
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of South Carolina at Columbia
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
041387846
City
Columbia
State
SC
Country
United States
Zip Code
29208