TY - JOUR
T1 - A closed vitrification system enables a murine ovarian follicle bank for high-throughput ovotoxicity screening, which identifies endocrine disrupting activity of microcystins
AU - Wang, Yingzheng
AU - Xu, Jingshan
AU - Stanley, Jessica E.
AU - Xu, Murong
AU - Brooks, Bryan W.
AU - Scott, Geoffrey I.
AU - Chatterjee, Saurabh
AU - Zhang, Qiang
AU - Zelinski, Mary B.
AU - Xiao, Shuo
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/4
Y1 - 2020/4
N2 - Increasing evidence reveals that a broad spectrum of environmental chemicals and pharmaceutical compounds cause female ovarian toxicity (ovotoxicity). The current gold standard of ovotoxicity testing largely relies on whole laboratory animals, but in vivo models are time consuming, costly, and present animal welfare concerns. We previously demonstrated that the 3D encapsulated in vitro follicle growth (eIVFG) is a robust in vitro model for ovotoxicity testing. However, the follicle preparation process is complex and highly dependent on technical skills. Here, we aimed to use vitrification method to cryopreserve murine immature follicles for a high-content eIVFG, chemical exposure, and ovotoxicity screening. Results indicated that a closed vitrification system combined with optimized vitrification protocols preserved mouse follicle viability and functionality and vitrified follicles exhibited comparable follicle and oocyte reproductive outcomes to freshly harvested follicles during eIVFG, including follicle survival and development, ovarian steroidogenesis, and oocyte maturation and ovulation. Moreover, vitrified follicles consistently responded to ovotoxic chemical, doxorubicin (DOX). We further used vitrified follicles to test the response of microcystins (MCs), an emerging category of environmental contaminants produced by cyanobacteria associated with harmful algal blooms (HABs), and found that different congeners of MCs exhibited differential ovotoxicities. In summary, our study demonstrates that vitrification enables a long-term-storage and ready-to-use ovarian follicle bank for high-throughput ovotoxicity screening, which identifies endocrine disrupting effects of MCs.
AB - Increasing evidence reveals that a broad spectrum of environmental chemicals and pharmaceutical compounds cause female ovarian toxicity (ovotoxicity). The current gold standard of ovotoxicity testing largely relies on whole laboratory animals, but in vivo models are time consuming, costly, and present animal welfare concerns. We previously demonstrated that the 3D encapsulated in vitro follicle growth (eIVFG) is a robust in vitro model for ovotoxicity testing. However, the follicle preparation process is complex and highly dependent on technical skills. Here, we aimed to use vitrification method to cryopreserve murine immature follicles for a high-content eIVFG, chemical exposure, and ovotoxicity screening. Results indicated that a closed vitrification system combined with optimized vitrification protocols preserved mouse follicle viability and functionality and vitrified follicles exhibited comparable follicle and oocyte reproductive outcomes to freshly harvested follicles during eIVFG, including follicle survival and development, ovarian steroidogenesis, and oocyte maturation and ovulation. Moreover, vitrified follicles consistently responded to ovotoxic chemical, doxorubicin (DOX). We further used vitrified follicles to test the response of microcystins (MCs), an emerging category of environmental contaminants produced by cyanobacteria associated with harmful algal blooms (HABs), and found that different congeners of MCs exhibited differential ovotoxicities. In summary, our study demonstrates that vitrification enables a long-term-storage and ready-to-use ovarian follicle bank for high-throughput ovotoxicity screening, which identifies endocrine disrupting effects of MCs.
KW - High-throughput
KW - In vitro follicle growth
KW - Microcystin
KW - Ovotoxicity
KW - Vitrification
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U2 - 10.1016/j.reprotox.2020.01.009
DO - 10.1016/j.reprotox.2020.01.009
M3 - Article
C2 - 32017985
AN - SCOPUS:85079006159
SN - 0890-6238
VL - 93
SP - 118
EP - 130
JO - Reproductive Toxicology
JF - Reproductive Toxicology
ER -