# An ovary-on-a-chip for understanding early folliculogenesis and reproductive toxicology in a large mammalian model

> **NIH NIH F32** · SMITHSONIAN INSTITUTION · 2020 · $40,578

## Abstract

PROJECT SUMMARY/ABSTRACT
 Recapitulation of folliculogenesis in vitro is of interest for both preserving human fertility and assessing the
influence of chemical contaminants on ovarian health. Although live offspring can be produced from oocytes
recovered from murine follicles grown in vitro, the larger size and protracted duration of folliculogenesis of large
mammals likely necessitates more complex culture requirements. The domestic cat will be used as a study model
because this species shares a number of anatomical and reproductive characteristics including follicle size and
oocyte nuclear configuration with the human. The proposed project will take advantage of ‘organ-on-chip’
microfluidic technology combined with somatic cell co-culture and my experience with 3-dimensional hydrogels
to recapitulate, as possible, in vivo conditions in an “ovary-on-a-chip”. Specifically, I propose to quantify the
rigidity of the domestic cat ovary via micropipette aspiration and atomic force microscopy and identify biomimetic
densities of alginate hydrogel that provide optimal structural support to primordial follicles. I will determine the
influence of rigidity and medium flow rate on in vitro folliculogenesis, and identify via tandem mass spectrometry
and RNA sequencing technologies, proteins and genes involved in follicle activation in culture. Comparison of
the dynamic system with traditional, static culture will allow me to improve understanding of the contributions of
structural rigidity (hydrogel density), medium flow (microfluidic chip), and the paracrine environment (produced
via co-culture) on follicle survival and activation in vitro (Aim 1). I then propose to evaluate the epigenetic impacts
(methylation of histones, key imprinted genes) of long-term culture in this system compared with traditional
culture, as well as determine the utility of the “ovary-on-a-chip” in ovarian toxicology studies, using the active
form of the chemotherapeutic cyclophosphamide in proof-of-concept studies (Aim 2). Together, these studies
advance understanding of contributions of the microenvironment on follicle development toward the goal of an
in vitro system for enhancing fertility preservation and reproductive toxicology.

## Key facts

- **NIH application ID:** 10267664
- **Project number:** 5F32HD090854-04
- **Recipient organization:** SMITHSONIAN INSTITUTION
- **Principal Investigator:** Jennifer Nagashima
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $40,578
- **Award type:** 5
- **Project period:** 2017-11-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10267664

## Citation

> US National Institutes of Health, RePORTER application 10267664, An ovary-on-a-chip for understanding early folliculogenesis and reproductive toxicology in a large mammalian model (5F32HD090854-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10267664. Licensed CC0.

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