Discovery of the Novel Heat Shock Factor HSF5: Kumamoto University Investigates a Potential Approach to Male Infertility
Researchers have discovered a novel heat shock factor (HSF), called HSF5, that plays a key role in completing meiosis and activating genes required for sperm formation. This discovery offers valuable insight into potential causes of spermatogenic cell dysfunction, a major contributor to male infertility. Unlike other typical heat shock factors, which primarily regulate gene expression under stressful conditions such as heat shock, HSF5 has a specific role in meiosis in male germ cells under non-stress conditions.
Researchers at Kumamoto University have identified a novel heat shock factor (HSF), called HSF5, that plays a key role in completing meiosis and activating genes required for sperm formation. This discovery offers valuable insight into potential causes of spermatogenic cell dysfunction, a major contributor to male infertility. Unlike other typical heat shock factors, which primarily regulate gene expression under stressful conditions such as heat shock, HSF5 has a specific role in meiosis in male germ cells under non-stress conditions.
During eukaryotic cell division, genomic information is distributed equally to daughter cells through mitosis. In the specialized cell division known as meiosis, which is essential for producing germ cells, that information is reduced by half. In male germ cells, sperm formation follows the completion of meiosis and involves multiple gene-regulation programs. However, the mechanisms regulating meiotic progression and the specific transcription factors involved remain poorly understood, creating major challenges in reproductive medicine, particularly in male infertility. To address these gaps, Professor Kei-ichiro Ishiguro, Assistant Professor Ryuki Shimada, and their research team sought to clarify the mechanisms of male meiosis leading to sperm formation, focusing on identifying and characterizing the relevant transcription factors.
In earlier research, the team identified the meiotic switch gene MEIOSIN, which activates the expression of hundreds of genes involved in sperm formation (Ishiguro et al., Developmental Cell, 2020). Among these genes, heat shock factors drew attention because the testes are sensitive to heat stress and are located outside the body, where the temperature is 3-4 degrees Celsius below the body's internal temperature of 37 degrees Celsius. Although the main roles of heat shock factors such as HSF1, HSF2, HSF3, and HSF4 are well established, the function of HSF5 remained unclear. "Whether HSF5 has functions similar to other heat shock factors or entirely different functions was an intriguing question, and answering it was the original aim of our research," Professor Ishiguro explained.
Surprisingly, unlike other stress-responsive HSFs, the study showed that HSF5 plays an essential role in meiotic prophase progression in male germ cells under non-stress conditions. During sperm formation, HSF5 supports progression through the pachytene stage, guides the meiotic program to completion, and activates genes associated with sperm formation.
Like other transcription factors, HSF5 binds to DNA promoters to regulate gene expression. HSF5 differs in its unique target specificity. The study showed that the DNA sequence it recognizes when binding to gene promoters differs from the sequences recognized by other typical HSF-family transcription factors.
Together, these findings highlight the atypical role of HSF5 in gene expression during male meiotic prophase.
The study findings were confirmed in experiments in mice, with the important recognition that HSF5 is also present in humans. Many potential causes of human infertility remain difficult to explain, particularly in cases of spermatogenic cell dysfunction. These findings are therefore expected to contribute significantly to understanding the mechanisms underlying male infertility.
News | Discovery of the Novel Heat Shock Factor HSF5: Kumamoto University Investigates a Potential Approach to Male Infertility
Discovery of the Novel Heat Shock Factor HSF5: Kumamoto University Investigates a Potential Approach to Male Infertility
Researchers have discovered a novel heat shock factor (HSF), called HSF5, that plays a key role in completing meiosis and activating genes required for sperm formation. This discovery offers valuable insight into potential causes of spermatogenic cell dysfunction, a major contributor to male infertility. Unlike other typical heat shock factors, which primarily regulate gene expression under stressful conditions such as heat shock, HSF5 has a specific role in meiosis in male germ cells under non-stress conditions.
Researchers at Kumamoto University have identified a novel heat shock factor (HSF), called HSF5, that plays a key role in completing meiosis and activating genes required for sperm formation. This discovery offers valuable insight into potential causes of spermatogenic cell dysfunction, a major contributor to male infertility. Unlike other typical heat shock factors, which primarily regulate gene expression under stressful conditions such as heat shock, HSF5 has a specific role in meiosis in male germ cells under non-stress conditions.
During eukaryotic cell division, genomic information is distributed equally to daughter cells through mitosis. In the specialized cell division known as meiosis, which is essential for producing germ cells, that information is reduced by half. In male germ cells, sperm formation follows the completion of meiosis and involves multiple gene-regulation programs. However, the mechanisms regulating meiotic progression and the specific transcription factors involved remain poorly understood, creating major challenges in reproductive medicine, particularly in male infertility. To address these gaps, Professor Kei-ichiro Ishiguro, Assistant Professor Ryuki Shimada, and their research team sought to clarify the mechanisms of male meiosis leading to sperm formation, focusing on identifying and characterizing the relevant transcription factors.
In earlier research, the team identified the meiotic switch gene MEIOSIN, which activates the expression of hundreds of genes involved in sperm formation (Ishiguro et al., Developmental Cell, 2020). Among these genes, heat shock factors drew attention because the testes are sensitive to heat stress and are located outside the body, where the temperature is 3-4 degrees Celsius below the body's internal temperature of 37 degrees Celsius. Although the main roles of heat shock factors such as HSF1, HSF2, HSF3, and HSF4 are well established, the function of HSF5 remained unclear. "Whether HSF5 has functions similar to other heat shock factors or entirely different functions was an intriguing question, and answering it was the original aim of our research," Professor Ishiguro explained.
Surprisingly, unlike other stress-responsive HSFs, the study showed that HSF5 plays an essential role in meiotic prophase progression in male germ cells under non-stress conditions. During sperm formation, HSF5 supports progression through the pachytene stage, guides the meiotic program to completion, and activates genes associated with sperm formation.
Like other transcription factors, HSF5 binds to DNA promoters to regulate gene expression. HSF5 differs in its unique target specificity. The study showed that the DNA sequence it recognizes when binding to gene promoters differs from the sequences recognized by other typical HSF-family transcription factors.
Together, these findings highlight the atypical role of HSF5 in gene expression during male meiotic prophase.
The study findings were confirmed in experiments in mice, with the important recognition that HSF5 is also present in humans. Many potential causes of human infertility remain difficult to explain, particularly in cases of spermatogenic cell dysfunction. These findings are therefore expected to contribute significantly to understanding the mechanisms underlying male infertility.
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