Organs-On-Chip Models of the Female Reproductive System

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.

The role of extracellular matrix in normal and pathological pregnancy: Future applications of microphysiological systems in reproductive medicine

“…31,32 If implantation occurs two or three days early or late, the risk of spontaneous abortion or pregnancy complications increases dramatically. 33,34 Steroid hormones 35 and other signaling molecules are coordinated during the menstrual cycle to create a “window of receptivity”, a period when conditions are optimal for embryo implantation. The composition of extracellular matrix in the endometrium helps to define this window of receptivity (Table 1, Figure 1(a)), which is marked by a reduction of matrix molecules that prevent adhesion and an increase in integrin expression to facilitate attachment between the embryo and uterine wall.…”

Role of Lipid Metabolism and Signaling in Mammalian Oocyte Maturation, Quality, and Acquisition of Competence

“…Recent advancement in organoid technology is revolutionizing knowledge about the function of biological systems. This organoid technology is recently being used to study clinical applications, toxicology studies and drug discoveries ( Xiao et al, 2017 ; Mancini and Pensabene, 2019 ). The use of microfluidics technology has already enabled researchers to study organ-on-chip that may lead to create multi-organoid-on-a chip plate form and even human-on-a-chip plate form ( Heidari-Khoei et al, 2020 ).…”

In vitro 3D Model of Female Reproductive Tract: An Overview and Future Aspect

“…Secreted proteins act as agonists or antagonists in the organism, initiating or suppressing physiological actions at the cellular level. As a result, cell-based assays, such as those utilized in a secretome-based method, are appropriate for measuring many types of responses (Mancini & Pensabene, 2019).…”

“…The vagina, cervix, uterus, endometrium, and fallopian tubes are all composed of mesodermal derivatives, whereas the ovaries are constructed of endoderm. The development, proliferation, and differentiation patterns of each of these tissues are distinct (Mancini & Pensabene, 2019).…”