Long-Term Advantages of Ovarian Reserve Maintenance and Follicle Development Using Adipose Tissue-Derived Stem Cells in Ovarian Tissue Transplantation

Abstract

(1) Background: Ovarian tissue transplantation with adipose tissue-derived stem cells (ASCs) has been shown to enhance graft vascularization and increase follicle survival after a short interval of 7 days. The aim of the present study was to investigate their long-term effects on primordial follicle pool maintenance and follicle development. (2) Methods: A total of 14 severe combined immunodeficient (SCID) mice were grafted with frozen-thawed human ovarian tissue with or without ASCs. Blood was taken monthly in order to quantify the anti-Müllerian hormone (AMH) and estradiol. After 6 months, all the grafts were retrieved and sent for histology and immunolabeling (AMH, AMH receptor II, estrogen receptors α and β, and c-kit/kit ligand). (3) Results: A significant upturn was observed in AMH and estradiol plasma levels 4 months after transplantation in both grafted groups. The primordial follicle pool was better preserved in the ASC group (41.86 ± 28.35) than in the standard transplantation group (9.65 ± 17.6, p < 0.05) compared to non-grafted controls (124.7 ± 140). (4) Conclusions: The use of ASCs prior to ovarian tissue transplantation yielded a larger primordial follicle pool and more physiological follicle distribution after long-term grafting. These findings suggested that ASC use might extend the ovarian tissue lifespan.

Keywords

• ovarian tissue transplantation
• adipose tissue-derived stem cells
• ASCs
• folliculogenesis
• endocrine restoration
• AMH