Abstract

Microfluidic-based technology attracts great interest in cell biology and medicine, in virtue of the ability to better mimic the in vivo cell microenvironment compared to conventional macroscale cell culture platforms. Recent Organs-on-chip (OoC) models allow to reproduce in vitro tissue and organ-level functions of living organs and systems. These models have been applied for the study of specific functions of the female reproductive tract, which is composed of several organs interconnected through intricate endocrine pathways and communication mechanisms. To date, a disease and toxicology study of this system has been difficult to perform. Thus, there is a compelling need to develop innovative platforms for the generation of disease model and for performing drug toxicity/screening in vitro studies. This review is focused on the analysis of recently published OoC models that recreate pathological and physiological characteristics of the female reproductive organs and tissues. These models aim to be used to assess changes in metabolic activity of the specific cell types and the effect of exposure to hormonal treatment or chemical substances on some aspects of reproduction and fertility. We examined these models in terms of device specifications, operating procedures, accuracy for studying the biochemical and functional activity of living tissues and the paracrine signalling that occurs within the different tissues. These models represent a powerful tool for understanding important diseases and syndromes affecting women all around the world. Immediate adoption of these models will allow to clarify diseases, causes and adverse events occurring during pregnancy such as pre-eclampsia, infertility or preterm birth, endometriosis and infertility.

Highlights

  • Novel three-dimensional (3D) cell culture devices, called “Organs-on-chip” (OoC) allow to reproduce in vitro tissue and organ-level functions of living organs and systems. These models have been applied for the study of specific functions of the female reproductive tract, which is composed of several organs interconnected through intricate endocrine pathways and communication mechanisms

  • human peritoneal mesothelial cells (HPMCs) lost contacts between each other, detached from the substrate, and disappeared under invasion of endometrial stromal cells (ESCs) em. These results suggest that in vivo ESCs are not able to adhere on healthy peritoneum and endometriosis is probably related to endometrial conditions, and to the pathogenic sites

  • In response to hormone treatment, the cells secreted levels of oestrogen and progesterone found in a typical menstrual cycle replicating the signalling that occurs among different female reproductive organs

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Summary

Introduction

Novel three-dimensional (3D) cell culture devices, called “Organs-on-chip” (OoC) allow to reproduce in vitro tissue and organ-level functions of living organs and systems. This review analyses examples of OoC models that allow the co-culture of different cell types and the in vitro study of pathological and physiological conditions of the female reproductive tract and changes occurring during conception and pregnancy. These models aim to be used to assess changes in metabolic activity of the specific cell types and the effect of exposure to hormonal treatment or chemical substances on some aspects of reproduction and fertility. TToo tthhiiss aaiimm,, tthhee ddeevveellooppmmeenntt ooff nnoovveell iinn vviittrroo ppllaattffoorrmmss aabbllee ttoo mmiimmiicc tthhee hhuummaann ppaatthhoopphhyyssiioollooggyy ooff ppeerriittoonneeaall eennddoommeettrriioossiiss rreepprreesseennttss aa ggrreeaatt ppootteennttiiaall ffoorr tthhee aannaallyyssiiss ooff tthhiiss ddiisseeaassee

The Female Reproductive System
Menstrual Cycle
Pregnancy and Foetal Membranes
Organs-On-Chip Models of the Female Reproductive Tract
Placenta-On-a-Chip Models
Artificial Uterus on a Microfluidic Chip
In Vitro Model of Endometriosis
Modelling the Human Reproductive Tract and the Menstrual Cycle
Integration of Scaffold and 3D Printed Structure
Findings
Conclusions

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