Human Ovarian Surface Epithelium Organoids as a Platform to Study Tissue Regeneration.

The ovarian surface epithelium (OSE), the outermost layer of the ovary, undergoes rupture during each ovulation and plays a crucial role in ovarian wound healing while restoring ovarian integrity. Additionally, the OSE may serve as the source of epithelial ovarian cancers. Although the OSE regenerative properties have been well studied in mice, understanding the precise mechanism of tissue repair in the human ovary remains hampered by limited access to human ovaries and suitable in vitro culture protocols. Tissue-specific organoids, miniaturized in vitro models replicating both structural and functional aspects of the original organ, offer new opportunities for studying organ physiology, disease modeling, and drug testing. Here, we describe a method to isolate primary human OSE (hOSE) from whole ovaries and establish hOSE organoids. We include a morphological and cellular characterization showing heterogeneity between donors. Additionally, we demonstrate the capacity of this culture method to evaluate hormonal effects on OSE-organoid growth over a 2-week period. This method may enable the discovery of factors contributing to OSE regeneration and facilitate patient-specific drug screenings for malignant OSE.

Bioengineered 3D Ovarian Models as Paramount Technology for Female Health Management and Reproduction.

Ovarian dysfunction poses significant threats to the health of female individuals. Ovarian failure can lead to infertility due to the lack or inefficient production of fertilizable eggs. In addition, the ovary produces hormones, such as estrogen and progesterone, that play crucial roles not only during pregnancy, but also in maintaining cardiovascular, bone, and cognitive health. Decline in estrogen and progesterone production due to ovarian dysfunction can result in menopausal-associated syndromes and lead to conditions, such as osteoporosis, cardiovascular disease, and Alzheimer's disease. Recent advances in the design of bioengineered three-dimensional (3D) ovarian models, such as ovarian organoids or artificial ovaries, have made it possible to mimic aspects of the cellular heterogeneity and functional characteristics of the ovary in vitro. These novel technologies are emerging as valuable tools for studying ovarian physiology and pathology and may provide alternatives for fertility preservation. Moreover, they may have the potential to restore aspects of ovarian function, improving the quality of life of the (aging) female population. This review focuses on the state of the art of 3D ovarian platforms, including the latest advances modeling female reproduction, female physiology, ovarian cancer, and drug screening.