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Reinke crystals are structures pathognomonic for Leydig cells, which have the important function of testosterone production and are vital for male reproductive health. These crystalline inclusions are thought to be of protein origin; however, the molecular composition has not yet been resolved. This review summarizes all available information regarding Reinke crystal's characteristics and aims to produce a comprehensive guide for research on this topic as well as to determine and discuss potential Reinke-protein candidates. Pubmed was thoroughly searched for all publications regarding Reinke crystals and 137 publications were identified. All publications were surveyed and all relevant information was included in the review. Along with the cytoplasm, structures that resemble Reinke crystals were also observed in the nucleus, suggesting that their formation depends only on protein concentration. Variations in tissue processing protocols could impact Reinke crystal microscopic visualization, which is an important factor in diagnosing Leydig cell disorders such as Leydig cell tumors. Reinke crystals appear to be hallmarks of normally differentiated, adult, Leydig or Leydig-like cells in humans, while some abnormal and nonhuman Leydig cells contain Reinke-like paracrystalline inclusions or crystalloids. These characteristics point to some differentially expressed proteins, which could be involved in Reinke crystal formation. Differential Reinke crystal and paracrystalline inclusion presence could also be due to small changes in protein structure or the cell environment. Further research is needed to solve the ongoing mystery of the Reinke crystal, which would enhance our knowledge of Leydig cell contribution in the pathogenesis of various male reproductive disorders and improve their diagnosis and treatment. © 2022 American Society of Andrology and European Academy of Andrology.


Ana Planinić, Tihana Marić, Ana Katušić Bojanac, Davor Ježek. Reinke crystals: Hallmarks of adult Leydig cells in humans. Andrology. 2022 Sep;10(6):1107-1120

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PMID: 35661438

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