Microphysiological modeling of the reproductive tract: a fertile endeavor
Sharon L Eddie1, J Julie Kim2, Teresa K Woodruff2
1Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60607, USA.
Abstract:
Preclinical toxicity testing in animal models is a cornerstone of the drug development process, yet it is often unable to predict adverse effects and tolerability issues in human subjects. Species-specific responses to investigational drugs have led researchers to utilize human tissues and cells to better estimate human toxicity. Unfortunately, human cell-derived models are imperfect because toxicity is assessed in isolation, removed from the normal physiologic microenvironment. Microphysiological modeling often referred to as 'organ-on-a-chip' or 'human-on-a-chip' places human tissue into a microfluidic system that mimics the complexity of human in vivo physiology, thereby allowing for toxicity testing on several cell types, tissues, and organs within a more biologically relevant environment. Here we describe important concepts when developing a repro-on-a-chip model. The development of female and male reproductive microfluidic systems is critical to sex-based in vitro toxicity and drug testing. This review addresses the biological and physiological aspects of the male and female reproductive systems in vivo and what should be considered when designing a microphysiological human-on-a-chip model. Additionally, interactions between the reproductive tract and other systems are explored, focusing on the impact of factors and hormones produced by the reproductive tract and disease pathophysiology.
Insights
New organ-on-a-chip models offer a more accurate way to test drug toxicity in human reproductive systems. These microphysiological systems better mimic in vivo conditions for improved in vitro toxicity assessments.
Area of Science:
- Toxicology
- Drug Development
- Biotechnology
Background:
- Preclinical toxicity testing in animals often fails to predict human responses.
- Existing human cell models lack the physiological microenvironment for accurate toxicity assessment.
- Organ-on-a-chip technology aims to replicate human physiology for better in vitro testing.
Purpose of the Study:
- To outline key considerations for developing reproductive system-on-a-chip models.
- To highlight the importance of sex-specific reproductive microfluidic systems for in vitro drug testing.
- To explore reproductive system interactions with other bodily systems in microphysiological models.
Main Methods:
- Review of in vivo male and female reproductive system biology and physiology.
- Discussion of design principles for reproductive microphysiological systems.
- Analysis of inter-system interactions and the impact of reproductive hormones and pathophysiology.
Main Results:
- Development of reproductive-on-a-chip models requires careful consideration of in vivo biological and physiological factors.
- Sex-specific reproductive microfluidic systems are crucial for accurate in vitro toxicity testing.
- Understanding systemic interactions is vital for comprehensive reproductive toxicity assessment.
Conclusions:
- Reproductive-on-a-chip models represent a significant advancement over traditional toxicity testing methods.
- These models provide a more biologically relevant platform for evaluating drug safety and efficacy.
- Further development is needed to fully integrate and validate these complex human-on-a-chip systems.
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