Maternal-fetal interface organoids: a new era in pregnancy research

The maternal-fetal interface is the core site of pregnancy occurrence and maintenance. Its complex physiological and pathological processes have long been concentrated in two-dimensional cell models and animal models. Organoids represent a novel in vitro three-dimensional model that offers a powerful platform for elucidating the complexities of human pregnancy, investigating pregnancy-related diseases, and developing novel treatment strategies. Organoids primarily employ pluripotent stem cells or tissue-derived progenitor cells to generate miniature "organs" that emulate the configuration of placental villi and/or endometrium under the influence of specific factors. The development of organoids has undergone substantial advancement. In the domain of reproductive medicine, maternal-fetal interface organoids have emerged as a versatile tool for simulating embryo implantation, elucidating maternal-fetal communication mechanisms, and facilitating etiological investigation and disease modeling of significant pregnancy complications, including recurrent miscarriage and preeclampsia. Furthermore, they can play an instrumental role in the realm of drug screening and research on vertical transmission of pathogens. The advancement of this field is contingent upon the synergistic integration of organoid culture technology and research methodologies, including imaging and multi-omics analysis. However, the field of maternal-fetal interface organoids is still in its nascent stages and faces many challenges. These include limitations in cell type completeness, tissue complexity, and functional maturity of existing models. In addition, there are standardization, reproducibility, and related ethical issues of culture. In the future, the development of this field will be driven by several key directions. These include the construction of additional physiological models, the integration of the immune and vascular systems, the promotion of standardization and clinical translation, and the establishment of clear ethical guidelines. These developments are expected to ultimately lead to breakthroughs in unlocking the early secrets of life's origins and preventing reproductive disorders.