Shuo Xiao, Ph.D., has recently developed a miniature model that provides a more accurate way to study the impact of environmental factors on infertility and women’s reproductive health. This innovative model, created with the support of several NIEHS grants, replicates the female reproductive system in a 3D format.
Organs-on-a-Chip Mimic Female Reproductive System
The device, known as an “organs-on-a-chip,” contains cells from four key reproductive organs—the ovaries, fallopian tubes, uterus, and cervix. These cells grow into organoids, 3D structures that simulate the function of real organs. The organoids are linked by small tubes that allow hormones and other signals to flow between them, mimicking natural interactions.
“This chip replicates the hormonal fluctuations and cellular changes that happen during a woman’s menstrual cycle,” Xiao explained. “By adding a mini 3D liver to the model, we can simulate how the reproductive system responds to a drug or toxin after it has been processed by the liver.”
Expanding Research on Endocrine Disruptors
Xiao’s latest research builds on his earlier studies on endocrine-disrupting chemicals, which are known to affect reproductive health. Under the mentorship of Xiaoqin Ye, Ph.D., Xiao earned his doctorate in female reproductive toxicology at the University of Georgia. There, he studied how these chemicals impact embryo implantation in the uterus, a vital step for a successful pregnancy.
For his postdoctoral research, Xiao expanded his focus to include other reproductive organs and aimed to reduce the use of animal models. His goal was to better understand the broader effects of environmental exposures on women’s reproductive health.
Improving Toxicity Testing with a New Approach
Xiao recognized the potential of the chip model for toxicity testing but realized the initial design required improvements to make it more efficient.
“With the original device, testing a chemical at different doses could take months,” said Xiao. “I wanted to streamline the process so we could quickly screen a wide range of chemicals.”
With support from an NIEHS career development award, Xiao moved to the University of South Carolina to refine the device for toxicity testing, focusing particularly on the ovarian follicle. This small sac, found in the ovaries, contains eggs and produces hormones necessary for ovulation and fertilization. Environmental factors that disrupt follicle hormone secretion or affect egg quality can harm fertility.
Working with mentors Jodi Flaws, Ph.D., and Mary Zelinski, Ph.D., Xiao developed a method called vitrification to freeze immature follicles for long-term storage. This process allows for the creation of an ovarian follicle bank, enabling high-throughput toxicity testing. Xiao’s work showed that when thawed, these preserved follicles functioned just like fresh ones, developing into 3D organoids, producing hormones, and even initiating ovulation.
Connecting Organs for Better Toxicity Simulation
Building on his earlier work and with additional funding from a second NIEHS grant, Xiao is now adding a liver organoid to the ovary-on-a-chip model. This addition will help better simulate how toxins, after being processed by the liver, affect the follicles, providing a more comprehensive understanding of environmental exposures on women’s reproductive health.
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