The Stage of Differentiation Into Mature Gametes During Gametogenesis in Vitro

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Published: 2025-08-12
DOI: https://doi.org/10.5281/zenodo.16808827
Keywords:
in vitro gametogenesis, stem cells, differentiation, meiosis, reproductive biology

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Jaba Tkemaladze
Longevity Clinic
https://orcid.org/0000-0001-8651-7243

Abstract

In vitro gametogenesis (IVG) stands as a revolutionary breakthrough in reproductive biology, offering the unprecedented capability to generate functional gametes from pluripotent stem cells (PSCs). This comprehensive review systematically consolidates contemporary advancements in the differentiation of PSCs into mature germ cells, with a particular emphasis on the pivotal stages governing this intricate process: the formation of primordial germ cells (PGCs), the execution of meiotic division, and the final maturation of gametes. Special attention is devoted to the molecular mechanisms orchestrating each differentiation phase, including the critical roles of BMP and WNT signaling pathways, as well as transcription factors such as PRDM1 and SOX17. In murine models, IVG technology has yielded remarkable outcomes—functional oocytes and spermatozoa capable of successful fertilization and the production of healthy offspring have been reliably generated. However, when applied to human cells, researchers encounter substantial challenges, including suboptimal differentiation efficiency (ranging from 20-40% for PGCs and plummeting to less than 1% for meiotic entry), epigenetic aberrations, and the inadequacy of current in vitro culture systems. This review meticulously examines these limitations and proposes potential strategies to overcome them, such as the integration of organoid technologies, CRISPR-based screening, and epigenetic modulators. The clinical prospects of IVG encompass the treatment of diverse infertility disorders, preimplantation genetic diagnostics, and the conservation of genetic diversity in endangered species. Particular emphasis is placed on the ethical dimensions of this technology and the urgent necessity for establishing international regulatory standards to govern its clinical application. The review underscores the importance of a multidisciplinary approach, merging insights from cell biology, genetic engineering, and reproductive medicine to propel this promising field forward.

Article Details

Issue

Vol. 1 No. 3 (2025)

Section

Reviews and Perspectives
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This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Articles published in Longevity Horizon fall under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0). This means authors retain their copyright while granting the journal the right to be the first publisher. Readers are permitted to share and distribute the work as long as proper credit is given. However, the content may not be altered, modified, or used for commercial purposes.

Author Biography

Jaba Tkemaladze, Longevity Clinic

Professor, Scientist, President of Longevity Alliance Georgia.

HOD at Longevity Clinic Inc.

Replacing old adult stem cells with induced and safe young adult stem cells.

World-renowned scientist. Developed the Centriolar theory of differentiation and the Centriolar theory of organism ageing. With acquired experience in both academia and industry.

Training in medicine at Tbilisi State Medical University and then at the Psychiatry Research Institute further deepened my knowledge in the laboratory of the Institute of Morphology. Namely, combined experimental and computational methods to study the ageing process and the various ways of manipulating age-related diseases and improvement of human health.

Also served as a Scientific Advisory Board Member in Georgia's Ministry of Defense and Longevity Alliance. Published over 90 scientific articles, given over 100 invited talks and received several awards.

How to Cite

Tkemaladze, J. (2025). The Stage of Differentiation Into Mature Gametes During Gametogenesis in Vitro. Longevity Horizon, 1(3). DOI:https://doi.org/10.5281/zenodo.16808827
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