Kumamoto University researchers have discovered a new Heat Shock Factor called HSF5 that is important for the completion of meiosis and the activation of genes necessary for sperm formation. This finding helps to understand the causes of spermatogenic failure, a major factor in male infertility. Unlike other Heat Shock Factors that mainly regulate gene expression in response to stress, HSF5 specifically plays a role in male germ production during meiosis under normal conditions.The novel Heat Shock Factor (HSF), known as HSF5, is highly important in the process of meiosis and in activating genes necessary for sperm formation. This discovery offers valuable insights into the root causes of spermatogenic failure, a major factor in male infertility. Unlike other typical Heat Shock Factors that mainly regulate gene expression in response to stress, like heat shock, HSF5 specifically plays a role in male germ production during meiosis under non-stressful conditions.
In eukaryotic cell division, genomic information is equally distributed to daughter cellDuring mitosis, the number of chromosomes remains the same, but during meiosis, a type of cell division necessary for germ cell production, the number of chromosomes is halved. This process is important for sperm formation and involves multiple gene regulatory programs. However, the specific transcription factors and mechanisms involved in meiotic progression are not well understood, which presents challenges in reproductive medicine, especially in relation to male infertility. Professor Kei-ichiro Ishiguro, Assistant Professor Ryuki Shimada, and their research team are working to address these gaps by clarifying the mechanisms that regulate male meiosis.The article explores the connection between heat shock factor and sperm production, with a focus on identifying and describing the transcription factors involved in the process. In a previous study, researchers pinpointed a gene called MEIOSIN, which plays a critical role in activating the expression of hundreds of genes that contribute to sperm formation (Ishiguro et al., Dev Cell 2020). One specific gene of interest is Heat Shock Factor, which has caught the attention of scientists due to the sensitivity of testes to heat stress. The testes, being externally positioned, are typically 3-4 degrees Celsius lower in temperature than the body’s internal temperature of 37 degrees Celsius. This means that Heat Shock Factors like HSF1, HSF2, HSF3, and others may play important roles in the process.HSF4 has been well identified, but the function of HSF5 remains unclear. Professor Ishiguro explains, “Whether HSF5 shares similar functions with other Heat Shock Factors, or exhibits entirely different functions poses an intriguing question, and addressing this question was the original intention of our study.”
Surprisingly, the study showed that HSF5 plays an essential role in the meiotic prophase progression in male germ cells under non-stress conditions, unlike other HSFs that respond to stress. HSF5 is required for progression beyond the pachytene stage during spermatogenesis, guiding the meiotic program towards completion and acting.The article discusses the role of HSF5 in regulating gene expression during meiotic prophase in males, specifically in relation to sperm formation. HSF5, a transcription factor, binds to DNA promoters to control gene expression, but its target specificity sets it apart from other members of the HSF family. The study’s findings were confirmed through experiments on mice, and it was noted that HSF5 also exists in humans. This research highlights the unusual function of HSF5 in gene expression and its potential significance in reproductive health.The exact causes of infertility in humans, particularly in cases of spermatogenic failure, are still not fully understood, but the results of this study are expected to significantly contribute to our understanding of the development of male infertility.
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