Artificial human ovary: advancing 3D ovarian culture for in vitro folliculogenesis, disease modelling and tissue regeneration

Abstract

Infertility affects over 186 million individuals worldwide, with female factors, particularly ovarian conditions, contributing to more than half of cases. Medically Assisted Reproduction (MAR) has transformed reproductive healthcare, yet significant challenges remain in understanding ovarian function and developing effective treatments for female infertility.This PhD thesis investigates innovative ex vivo culture strategies for ovarian cortical tissue, aiming to support the in vitro maturation of early follicles. Using cryopreserved-thawed ovarian tissue donated by transmasculine individuals, the research explores the potential of artificial ovary models for fertility preservation. Key findings include the identification of tissue fibrosis as a challenge in ovarian tissue culture and promising results regarding the use of Metformin to manage fibrotic ovarian tissue associated with aging and metabolic dysfunctions. Additionally, the thesis introduces a novel protocol for generating ovarian surface epithelium (OSE) organoids that retain donor-specific characteristics, highlighting their potential for personalized medicine.

These findings represent a significant step forward in understanding ovarian physiology and developing innovative fertility preservation strategies. Beyond their scientific impact, they hold important social and medical relevance by underscoring the challenges that remain in developing in vitro folliculogenesis protocols and emphasizing the importance of considering the donor's metabolic and endocrine state, as well as the tissue source. Finally, by promoting more personalized and effective reproductive options while minimizing the use of animal models, this work contributes to advancing reproductive healthcare in an inclusive, ethical, and patient-centered manner.