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Bogdan Doroftei Department of Mother and Child, Faculty of Medicine, University of Medicine and Pharmacy Grigore T. Popa, Iasi, Romania
Clinical Hospital of Obstetrics and Gynecology Cuza Voda, Iasi, Romania
Origyn Fertility Center, Iasi, Romania

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Ovidiu-Dumitru Ilie Department of Mother and Child, Faculty of Medicine, University of Medicine and Pharmacy Grigore T. Popa, Iasi, Romania

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Sergiu Timofeiov Department of Surgery, Faculty of Medicine, University of Medicine and Pharmacy Grigore T. Popa, Iasi, Romania
3rd Surgical Unit, St. Spiridon County Emergency Clinical Hospital, Iasi, Romania

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Ana-Maria Dabuleanu Clinical Hospital of Obstetrics and Gynecology Cuza Voda, Iasi, Romania
Origyn Fertility Center, Iasi, Romania

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Ioana-Sadyie Scripcariu Department of Mother and Child, Faculty of Medicine, University of Medicine and Pharmacy Grigore T. Popa, Iasi, Romania

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Romeo Micu Department of Human Assisted Reproduction of 1st Gynecology Clinic, University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania

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Elena Tataranu Faculty of Medicine and Biological Sciences, Stefan cel Mare University of Suceava, Suceava, Romania

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In brief

Alpha-ketoglutarate is a common metabolite in the tricarboxylic acid cycle and is central in modulating the reproductive potential in animal models. The present scoping review systematically covers the spectrum of a wide range of evidence from different viewpoints, focusing on the underlying processes and mechanisms of the developmental framework, aiming to fill the gaps within the existing literature.

Abstract

Alpha-ketoglutarate is an important intermediate molecule in the tricarboxylic acid cycle with a prominent role in distinct biological processes such as cellular energy metabolism, epigenetic regulation, and signaling pathways. We conducted a registered scoping review (OSF: osf.io/b8nyt) to explore the impact of exogenous supplementation on reproductive capabilities. Our strategy included evaluating the main research literature from different databases like PubMed-MEDLINE, Web of ScienceTM, Scopus, and Excerpta Medica dataBASE using a specific systematic layout to encompass all investigations based on experimental models and critically compare the results. Twenty-one studies were included in the main body of this manuscript, which revealed that exogenous supplementation induced dose- and sex-dependent modifications. This metabolite modulates the expression of pluripotency genes, thus controlling stem cells’ self-renewal, differentiation, and reprogramming dynamics, while also alleviating structural transformations induced by exposure to heavy metals and other inhibitors. This significantly demonstrated a direct influence of alpha-ketoglutarate in mitigating oxidative stress and prolonging the lifespan, consequently supporting metabolic and endocrine adjustments. It influences oocyte quality and quantity, delays reproductive aging, and establishes an optimal competence framework for development with minimal risk of failure. Therefore, alpha-ketoglutarate is linked to improving reproductive performance, but further studies are needed due to a lack of studies on humans.

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