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  2. SOX30 Governs Synaptonemal Complex Assembly and Homologous Recombination in Male Meiosis

SOX30 Governs Synaptonemal Complex Assembly and Homologous Recombination in Male Meiosis

  • Cell Prolif. 2025 Dec 30:e70158. doi: 10.1111/cpr.70158.
Kangle Liu 1 2 3 Wenfeng Zhang 1 2 3 Xiao Jiang 1 2 3 Jianping Chen 1 2 3 Lei Zhu 1 2 3 Zhonghao Zhang 1 2 3 Jing Gu 1 2 3 Lulu Guo 1 2 3 Lin Ao 1 2 3 Qing Chen 1 2 3 Lei Sun 1 2 3 Yuhan Hu 1 2 3 Xin Wang 1 2 3 Yaxin Liu 1 2 3 Jia Cao 1 2 3 Fei Han 4 Jinyi Liu 1 2 3
Affiliations

Affiliations

  • 1 Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China.
  • 2 State Key Lab of Trauma and Chemical Poisoning, and Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Army Medical University, Chongqing, China.
  • 3 Chongqing Municipal Key Laboratory of Hygiene Toxicology of Higher Education, Chongqing, China.
  • 4 Joint International Research Laboratory of Reproduction and Development of the Ministry of Education, School of Public Health, Chongqing Medical University, Chongqing, China.
Abstract

Meiosis, a specialised form of cell division, is essential for sexual reproduction, which requires the proper formation of synaptonemal complex (SC) and homologous recombination (HR). However, the regulatory mechanisms underlying these processes remain incompletely understood. Here, we demonstrate that SOX30 is a key transcriptional regulator of male meiotic synapsis and recombination. In Sox30-knockout mice, zygotene spermatocytes accumulate with synapsis defects. SOX30 deficiency disrupts the SC central element components SYCE1, SYCE2, and TEX12 distribution. Furthermore, disrupted γ-H2AX distribution reveals impaired DNA double-strand break repair and the persistence of recombination proteins RAD51 and RPA2 in late spermatocytes confirms defective homologous recombination repair (HRR) which results in reduced crossover formation in Sox30-knockout mice spermatocytes. Mechanistically, SOX30 directly binds to SYCE1/SYCE2 promoters to modulate their transcription, thereby regulating SC assembly and HRR. Restoring SOX30 expression effectively rescues meiotic defects. Importantly, transcriptome co-expression analysis in non-obstructive azoospermia (NOA) testes identifies SOX30 as a central regulator of NOA transcriptional networks. Collectively, these findings underscore SOX30's crucial role in meiotic synapsis and recombination, highlighting its therapeutic potential for NOA.

Keywords

SOX30; homologous recombination; meiosis; spermatogenesis; synaptonemal complex.

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