# An ovary-on-a-chip to identify ovarian toxicity

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2021 · $354,358

## Abstract

PROJECT SUMMARY
The ovary and its functional unit, the follicles, are critical for the secretion of sex steroids and peptide hormones
as well as the maturation and release of oocytes for ovulation and fertilization. Increasing evidence has revealed
that a wide spectrum of environmental chemicals and pharmaceuticals cause ovarian toxicity (ovotoxicity) and
heighten the risk of premature ovarian failure, hormonal imbalance, and infertility in both reproductive aged
women and prepubertal girls. With over 85,000 chemicals used in consumer products as well as emerging
contaminants such as harmful algal bloom (HAB) toxins, there are few means to screen for potential toxicity to
the ovaries. We have previously developed an ovary-on-a-chip (OvaryChip) that maintains the 3D architecture
of follicles and produces human menstrual cycle-like follicle development, hormone secretion, oocyte maturation,
ovulation, and luteinization. Yet, one remaining challenge of this innovative model is the critical need to
accelerate throughput. The central hypothesis of this research is that in vitro microfluidic follicular
cultures can be used to identify novel mechanisms of ovarian toxicity for environmental toxicants. In
Aim 1, we will integrate follicle vitrification, 3D in vitro follicle growth, and a new OvaryChip with high-content
culture and imaging to develop a high-throughput ovotoxicity testing of growing follicles. In Aim 2, we will develop
a new OvaryChip for ovotoxicity testing of primordial follicles by using triple transgenic mouse ovarian explants.
In Aim 3, we will develop a liver-ovary-on-a-chip to incorporate liver metabolism into ovotoxicity testing. In these
studies, we will assess follicle and oocyte reproductive outcomes at morphological, functional, and molecular
levels for 1) chemicals with known ovotoxicities (validation studies) and 2) novel HAB toxins alone and in mixtures.
These studies are critically significant because the OvaryChip models will (1) translate a bench assay for a single
compound into a robust high-throughput ovotoxicity screening platform; (2) reveal novel insight into chemical-
induced ovotoxicity (stage- and metabolite-dependent mechanisms); (3) minimize the cost and use of whole
animals; and (4) prioritize chemicals of high ovotoxicity concern, including HAB toxins, for further risk assessment.

## Key facts

- **NIH application ID:** 10210586
- **Project number:** 1R01ES032144-01A1
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Shuo Xiao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $354,358
- **Award type:** 1
- **Project period:** 2021-09-20 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10210586

## Citation

> US National Institutes of Health, RePORTER application 10210586, An ovary-on-a-chip to identify ovarian toxicity (1R01ES032144-01A1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10210586. Licensed CC0.

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