Abstract
In the last few decades, stem cell therapy has grown as a boon for many pathological complications including female reproductive disorders. In this review, a brief description of available strategies that are related to stem cell-based in vitro oocyte-like cell (OLC) development are given. We have tried to cover all the aspects and latest updates of the in vitro OLC developmental methodologies, marker profiling, available disease models, and in vivo efficacies, with a special focus on mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs) usage. The differentiation abilities of both the ovarian and non-ovarian stem cell sources under various induction conditions have shown different effects on morphological alterations, proliferation- and size-associated developments, hormonal secretions under gonadotropic stimulations, and their neo-oogenesis or folliculogenesis abilities after in vivo transplantations. The attainment of characters like oocyte-like morphology, size expansion, and meiosis initiation have been found to be major obstacles during in vitro oogenesis. A number of reports have either lacked in vivo studies or have shown their functional incapability to produce viable and healthy offspring. Though researchers have gained many valuable insights regarding in vitro gametogenesis, still there are many things to do to make stem cell-derived OLCs fully functional.
Highlights
In the last few decades, the in vitro development of oocyte-like cells (OLCs) with the ability to cure female reproductive disorders by neo-oogenesis and folliculogenesis has been the main focus of reproductive and stem cell scientists
Researchers have succeeded in deriving primordial germ-like cells (PGCLCs), follicle-like cells (FLCs), and OLCs, as well as in treating animal disease models by using embryonic stem cells (ESCs), induced pluripotent stem cells, and neonatal and adult ovarian stem cell sources from different species including humans [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16], mice [17,18,19,20,21,22,23,24], porcine [25,26,27,28,29], bovines [30,31], and goats [32]
This study demonstrated the innate ability of follicular fluid (FF)-derived cells to possess stemness properties, the development of round OLC-like structures, and high estradiol secretion by freshly seeded cells followed by gradually decreased levels and positive expression of zona pellucida markers, i.e., ZP2 and ZP3
Summary
In the last few decades, the in vitro development of oocyte-like cells (OLCs) with the ability to cure female reproductive disorders by neo-oogenesis and folliculogenesis has been the main focus of reproductive and stem cell scientists. Researchers have succeeded in isolating cells from the ovarian surface epithelium (OSE) and the ovarian cortex, and they have utilized whole ovaries by using mechanical and enzymatic degradation methods [1,22,23,29,31,33,34,35] By culturing these cells in specific media or inducing the ectopic expression of some transcriptional factors, OLCs that attained oocyte-like morphology but exhibited germ cell-specific marker expression both at messenger ribonucleic acid (mRNA) and protein levels have been generated [29]. The forced ectopic expression of transcription factors to direct ovarian and non-ovarian stem cells towards in vitro oogenesis has been utilized on various targets including exit from pluripotency, PGCLC development, the initiation of meiosis (haploid cell generation), OLC differentiation, OLC maturation, and, the utilization of these female germ cells to produce viable and healthy offspring. MEF: mouse embryonic fibroblast; GCs: granulosa cells; OLCs: oocyte-like cells; and PGCs: primordial germ cells
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