Shuo Xiao, Ph.D., has created a groundbreaking miniature model designed to study how environmental factors influence infertility and reproductive health in women. These 3D models, developed with the support of National Institute of Environmental Health Sciences (NIEHS) grants, replicate the female reproductive system.
The innovative “organs-on-a-chip” device consists of cells from four reproductive organs — the ovaries, fallopian tubes, uterus, and cervix — that form organoids. These 3D structures simulate the functions of real organs and are connected by tiny tubes that carry hormones and signals between them.
“The miniature chip mirrors the hormone fluctuations and cellular changes that occur during a woman’s menstrual cycle,” Xiao explained. “When we add a mini 3D liver to the device, it allows us to see how the reproductive system reacts to a drug or toxin after the liver metabolizes it.”
Expanding the Scope Beyond Endocrine Disruptors
This new model builds on Xiao’s earlier research, which focused on the effects of endocrine-disrupting chemicals. Under the guidance of Xiaoqin Ye, Ph.D., Xiao earned his doctorate in female reproductive toxicology at the University of Georgia, where he studied how these chemicals impact embryo implantation in the uterus, a vital step in achieving pregnancy.
In his postdoctoral research, Xiao expanded his focus to include all organs in the female reproductive system and worked to minimize the use of animal models in his studies.
Optimizing the Model for Toxicity Testing
Xiao recognized the potential of his chip model for chemical toxicity testing, but he knew improvements were necessary.
“With the initial model, it could take months to test a chemical at different doses,” Xiao said. “I wanted to optimize the device so we could quickly screen a wide range of chemicals.”
Thanks to an NIEHS career development award, Xiao moved to the University of South Carolina, where he refined one key component of the device: the follicle. The follicle, a small sac in the ovary, contains eggs and produces hormones essential for ovulation and fertilization. Environmental factors that affect follicle hormone production or egg quality can decrease a woman’s fertility.
Under the mentorship of Jodi Flaws, Ph.D., and Mary Zelinski, Ph.D., Xiao developed a method called vitrification, which freezes immature follicles for long-term storage. This creates an ovarian follicle bank for efficient chemical toxicity screening. Xiao demonstrated that thawed follicles grown in an “ovary-on-a-chip” environment behaved similarly to fresh follicles, releasing reproductive hormones, initiating ovulation, and producing mature eggs.
Mimicking the Full Body Response
Inspired by his earlier research and supported by a second NIEHS grant, Xiao is now working to integrate a liver organoid into his model. This addition will help replicate how toxins, after being processed by the liver, affect the follicles and reproductive system. The goal is to create a more complete and accurate model for understanding environmental impacts on women’s fertility.
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