The biofabrication of a 3D in vitro human oviduct model to study infertility and factors affecting embryo development

Project Information

OviChip

Grant agreement ID: 101043014

DOI

10.3030/101043014

EC signature date 8 November 2022

Start date 1 January 2023

End date 31 December 2027

Funded under

• European Research Council (ERC)

Total cost

€ 2 318 530,00

EU contribution

€ 2 318 530,00

Coordinated by

UNIVERSITEIT MAASTRICHT
Netherlands

Periodic Reporting for period 1 - OviChip (The biofabrication of a 3D in vitro human oviduct model to study infertility and factors affecting embryo development)

Reporting period: 2023-01-01 to 2025-06-30

Summary of the context and overall objectives of the project

Despite being viewed as a simple transport conduit, the oviduct can determine a successful pregnancy and has a life-long impact on our health and wellbeing. Also called the fallopian tube, our understanding of tubal function remains limited, owing to the ethical limitations of human studies and the poor translations of animal studies to people. The objective of the OviChip project is to create the first full-scale 3D in vitro model of the oviduct that can address our knowledge gap. The oviduct selects healthy sperm and hosts the first embryonic cell divisions, setting the stage for fetal development and health in our adult life. Epigenetic factors can trigger genetic defects in these first moments that lead to unsuccessful pregnancies or ailments such as Alzheimer’s, Diabetes, and schizophrenia. When oviduct function is compromised, such as through a Chlamydia Trachomatis infection, infertility can arise. A common recourse for prospective parents is in vitro fertilization (IVF). However, IVF success rates have plateaued at 30% for the past decade and concerns have emerged about the epigenetic impact IVF has on a child’s health. Therefore, to improve embryo viability and IVF outcomes or to avoid IVF by addressing tubal pathologies, our knowledge gap about oviduct function must be addressed. The OviChip project will develop biofabrication technologies to create a 3D model that respects the structural and biological elements of the oviduct from a meso to micron scale. The anticipated outcomes include: 1) the validation of new biofabrication approaches; 2) a better understanding of Chlamydia-associated tubal pathologies; 3) insight into the oviduct microenvironment with respect to sperm selection and epigenetic factors affecting embryogenesis. The OviChip will strive for unprecedented biomimicry and functional readout, setting new standards for tissue engineering. Most importantly, this will provide a unique avenue to fundamental answers that impact patients.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The OviChip project has so far developed multiple in vitro oviduct model by combining expertise from bioengineering and cell biology to create representative and functional platforms. Design features of the OviChip models were determined by analyzing mouse and human oviduct tissues and a combination of PDMS and hydrogel was used to successfully replicated key geometric, structural, and mechanical features of the oviducts of both species. At the same time, the same donor issue was used to generate an ideal cell source of oviduct epithelial cells (OECs) by isolating and culturing OECs to form organoids, which we show can be successfully integrated into the OviChip device. This creates a physiologically relevant environment where oviduct epithelial cells (OECs) could grow and function.

Ongoing innovations include establishing dynamic sex hormone gradients within the device, crucial for studying hormonal influences on cellular behavior. The project team is also exploring advanced microscopy techniques to visualize cell function in real time, with the aim of contributing to a deeper understanding of reproductive biology and disease modeling. To this end, an advanced multiphoton NIKON microscope has been purchased for the project, configured specifically for organ-on-chip tissue models. The team has taken the initial steps of creating a Chlamydia infection model, allowing to observe the progression of this bacterial infection within the OviChip and with plans to investigate tubal scarring. The project is also at the early stages of investigating reproductive processes within the Ovichip. These studies will provide unprecedented insights into the early stages of reproduction both healthy and disease conditions.

With its adaptable design, the OviChip is promising a wide range of future applications. This project is not only advancing reproductive biology but also setting a new standard for organ-on-chip technology and paving the way for breakthroughs in biomedical research.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The expected results of this project include a better understanding of first moments after conception and the importance of the microenvironment of the Fallopian tube, with expected implications for current IVF practices. To translate such findings to a clinical setting, IPR and commercialization support would be required, along with further research and regulatory support would be needed. Furthermore, a better understanding of sperm migration and embryo transport within the Fallopian tube is expected, both of which are largely unknown in humans. The targeted aim to understand the impact of Chlamydia-induced tubal scarring on these important events. We expect these results will provide new potential targets for therapies to counter the infertility caused by tubal scarring. To fully investigate and develop therapeutic candidates, further research would be required.