2. Academic Validation
  3. PhospholipaseA2VI mediates the lipid peroxidation-ferroptosis axis to regulate rooster sperm motility

PhospholipaseA2VI mediates the lipid peroxidation-ferroptosis axis to regulate rooster sperm motility

  • Poult Sci. 2025 Aug 28;104(11):105751. doi: 10.1016/j.psj.2025.105751.
Jiwei Li 1,  Pingquan Liu 2,  Juan Zhang 3,  Yadong Tian 2,  Guirong Sun 2,  Xiangtao Kang 2,  Donghua Li 2,  Yaling Gu 4
Affiliations

Affiliations

  • 1 College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China; Henan Key Laboratory for Innovation and Utilization of Chicken Germplasm Resources, College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China.
  • 2 Henan Key Laboratory for Innovation and Utilization of Chicken Germplasm Resources, College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China.
  • 3 College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China.
  • 4 College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China. Electronic address: guyl@nxu.edu.cn.
PMID: 40961763 DOI: 10.1016/j.psj.2025.105751
Abstract

We identified individuals with substantial differences in sperm motility among high-motility sperm samples preserved under various conditions. Phospholipase A2 group VI (PLA2G6) was upregulated in the low-motility group (LMG) by integrating seminal plasma metabolome and epididymal transcriptome data. LMG exhibited increased malondialdehyde and Fe²⁺ levels, whereas the sperm's membrane integrity and Glutathione Peroxidase 4's activity were reduced. Targeted PLA2G6 activity inhibition led to a substantial reduction in PLA2G6 activity and lysophosphatidylcholine levels in the SP, accompanied by improved sperm motility and membrane integrity, extended in vitro survival, and increased fertilization efficiency. PLA2G6 promoted sperm motility loss by hydrolyzing phosphatidylcholine to generate lysophosphatidylcholine and polyunsaturated fatty acids, ultimately resulting in lipid peroxidation and Ferroptosis. We provide new insights into the mechanisms underlying sperm motility regulation, a potential strategy for extending the artificial insemination window, and developing semen preservation technologies based on Ferroptosis regulation.

Keywords

Ferroptosis; Lipid peroxidation; Phospholipase A2 group VI; Sperm motility.

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