P15 | PHB/JAK/H3Y41PH AXIS REGULATES MEIOTIC RECOMBINATION IN SPERMATOGENESIS
Previously, we have shown that human sperm Prohibitin (PHB) expression is significantly negatively correlated with mitochondrial ROS levels but positively correlated with mitochondrial membrane potential and motility. However, the possible role of PHB in mammalian spermatogenesis has not been inves...
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| Language: | English |
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PAGEPress Publications
2025-08-01
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| Series: | European Journal of Histochemistry |
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| Online Access: | https://www.ejh.it/ejh/article/view/4335 |
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Previously, we have shown that human sperm Prohibitin (PHB) expression is significantly negatively correlated with mitochondrial ROS levels but positively correlated with mitochondrial membrane potential and motility. However, the possible role of PHB in mammalian spermatogenesis has not been investigated. Here we document the presence of PHB in spermatocytes and its functional roles in meiosis by generating the first male germ cell-specific PhbcKO mouse. Loss of PHB in spermatocytes resulted in complete male infertility, associated with not only meiotic pachytene arrest, but also apoptosis resulting from mitochondrial morphology and function impairment. Our mechanistic studies show that PHB in spermatocytes regulates the expression of STAG3, a key component of the meiotic cohesin complex, via a non-canonical JAK/STAT pathway, and consequently promotes meiotic DSB repair and homologous recombination. Furthermore, the PHB/JAK2 axis was found as a novel mechanism in the maintenance of stabilization of meiotic STAG3 cohesin complex and the modulation of heterochromatin formation in spermatocytes during meiosis. The observed JAK2-mediated epigenetic changes in histone modifications, reflected in a reduction of histone 3 tyrosine 41 phosphorylation (H3Y41ph) and a retention of H3K9me3 at the Stag3 locus, could be responsible for Stag3 dysregulation in spermatocytes with the loss of PHB.
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| format | Article |
| id | doaj-art-56b1aa4e2dd9449d9468f34a733ee2e5 |
| institution | Kabale University |
| issn | 1121-760X 2038-8306 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | PAGEPress Publications |
| record_format | Article |
| series | European Journal of Histochemistry |
| spelling | doaj-art-56b1aa4e2dd9449d9468f34a733ee2e52025-08-23T11:19:10ZengPAGEPress PublicationsEuropean Journal of Histochemistry1121-760X2038-83062025-08-0169s210.4081/ejh.2025.4335P15 | PHB/JAK/H3Y41PH AXIS REGULATES MEIOTIC RECOMBINATION IN SPERMATOGENESIS Previously, we have shown that human sperm Prohibitin (PHB) expression is significantly negatively correlated with mitochondrial ROS levels but positively correlated with mitochondrial membrane potential and motility. However, the possible role of PHB in mammalian spermatogenesis has not been investigated. Here we document the presence of PHB in spermatocytes and its functional roles in meiosis by generating the first male germ cell-specific PhbcKO mouse. Loss of PHB in spermatocytes resulted in complete male infertility, associated with not only meiotic pachytene arrest, but also apoptosis resulting from mitochondrial morphology and function impairment. Our mechanistic studies show that PHB in spermatocytes regulates the expression of STAG3, a key component of the meiotic cohesin complex, via a non-canonical JAK/STAT pathway, and consequently promotes meiotic DSB repair and homologous recombination. Furthermore, the PHB/JAK2 axis was found as a novel mechanism in the maintenance of stabilization of meiotic STAG3 cohesin complex and the modulation of heterochromatin formation in spermatocytes during meiosis. The observed JAK2-mediated epigenetic changes in histone modifications, reflected in a reduction of histone 3 tyrosine 41 phosphorylation (H3Y41ph) and a retention of H3K9me3 at the Stag3 locus, could be responsible for Stag3 dysregulation in spermatocytes with the loss of PHB. https://www.ejh.it/ejh/article/view/4335- |
| spellingShingle | P15 | PHB/JAK/H3Y41PH AXIS REGULATES MEIOTIC RECOMBINATION IN SPERMATOGENESIS European Journal of Histochemistry - |
| title | P15 | PHB/JAK/H3Y41PH AXIS REGULATES MEIOTIC RECOMBINATION IN SPERMATOGENESIS |
| title_full | P15 | PHB/JAK/H3Y41PH AXIS REGULATES MEIOTIC RECOMBINATION IN SPERMATOGENESIS |
| title_fullStr | P15 | PHB/JAK/H3Y41PH AXIS REGULATES MEIOTIC RECOMBINATION IN SPERMATOGENESIS |
| title_full_unstemmed | P15 | PHB/JAK/H3Y41PH AXIS REGULATES MEIOTIC RECOMBINATION IN SPERMATOGENESIS |
| title_short | P15 | PHB/JAK/H3Y41PH AXIS REGULATES MEIOTIC RECOMBINATION IN SPERMATOGENESIS |
| title_sort | p15 phb jak h3y41ph axis regulates meiotic recombination in spermatogenesis |
| topic | - |
| url | https://www.ejh.it/ejh/article/view/4335 |