LPA deficiency in follicular fluid linked to impaired oocyte maturation through BCAA metabolism-mediated mitochondrial dysfunction

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ID: 324834
2026
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Abstract
Abstract Lysophosphatidic acid (LPA) is known to be crucial for oocyte developmental competence, but the underlying molecular mechanisms remain unclear. In this study, we investigated the mechanistic relationship between follicular fluid LPA levels and oocyte quality determinants using a cohort of assisted reproductive technology patients, correlating LPA abundance with follicle sensitivity indices. Transcriptome sequencing and metabolic flux analyses compared low versus high LPA groups. Functional validation employed gabapentin-mediated inhibition of branched-chain amino acid (BCAA) catabolism in oocytes, assessing meiotic maturation, mitochondrial function, and oxidative stress. We found that reduced LPA levels were associated with significant suppression of BCAA catabolic pathways, leading to accumulation of valine and leucine. Gabapentin inhibition of BCAA oxidation recapitulated the low-LPA phenotype, inducing severe meiotic defects characterized by aberrant spindle assembly, chromosomal misalignment, and pronounced DNA damage. These oocytes also exhibited mitochondrial dysfunction with disrupted organellar distribution and severely compromised membrane polarization, along with elevated reactive oxygen species. Our findings indicate that impaired BCAA metabolism under low-LPA conditions compromises oocyte quality through mitochondrial dysfunction and oxidative stress, suggesting LPA as a potential modulator of metabolic pathways during oocyte maturation and also suggesting novel therapeutic targets for improving assisted reproduction outcomes.
Reference Key
openalex_W7202340190 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Huanyu Yan, Jihong Yang, Chuchu Hong, Yangbai Li, Fei Mao, Xi Wang, Yun Qian
Journal journal of molecular cell biology
Year 2026
DOI
10.1093/jmcb/mjag028
URL
https://doi.org/10.1093/jmcb/mjag028
Keywords Keywords not found

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