Exploring the black box of human reproduction: endometrial organoids and assembloids - generation, implantation modeling, and future clinical perspectives

Front Cell Dev Biol. 2024 Oct 23:12:1482054. doi: 10.3389/fcell.2024.1482054. eCollection 2024.

Abstract

One of the critical processes in human reproduction that is still poorly understood is implantation. The implantation of an early human embryo is considered a significant limitation of successful pregnancy. Therefore, researchers are trying to develop an ideal model of endometrium in vitro that can mimic the endometrial micro-environment in vivo as much as possible. The ultimate goal of endometrial modeling is to study the molecular interactions at the embryo-maternal interface and to use this model as an in vitro diagnostic tool for infertility. Significant progress has been made over the years in generating such models. The first experiments of endometrial modeling involved animal models, which are undoubtedly valuable, but at the same time, their dissimilarities with human tissue represent a significant obstacle to further research. This fact led researchers to develop basic monolayer coculture systems using uterine cells obtained from biopsies and, later on, complex and multilayer coculture models. With successful tissue engineering methods and various cultivation systems, it is possible to form endometrial two-dimensional (2D) models to three-dimensional (3D) organoids and novel assembloids that can recapitulate many aspects of endometrial tissue architecture and cell composition. These organoids have already helped to provide new insight into the embryo-endometrium interplay. The main aim of this paper is a comprehensive review of past and current approaches to endometrial model generation, their feasibility, and potential clinical application for infertility treatment.

Keywords: 3D modeling; assembloids; endometrial organoids; implantation modeling; infertility.

Publication types

  • Review

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by a grant from The Ministry of Education, Research, Development and Youth of the Slovak Republic No. VEGA 1/0625/23, entitled “Immunologically active endometrial cells in the context of embryo implantation and their targeting in the treatment of infertility,” and by grant No. VEGA 1/0347/24 entitled Morphological and Molecular-Biological Study of Hormonally Dependant Processes and Immune Functions in the Uterine Tube Wall and the Interactions Between the Wall of the Uterine Tube and Germ Cells.