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Effect of Sperm DNA Fragmentation and Chromatin Decondensation on PLCζ Efficacy in Infertile Patients

Soukaina Azil1,2, Ismail Kaarouch3, Debbie Montjean4

  • 1Immunopathology-Immunotherapy-Immunomonitoring Laboratory, Faculty of Medicine, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco.

Current Issues in Molecular Biology
|September 29, 2025
PubMed

Insights

Phospholipase C zeta (PLCζ) deficiency is linked to male infertility. Reduced PLCζ levels and altered localization in sperm correlate with DNA fragmentation and chromatin decondensation, potentially causing fertilization failure.

Area of Science:

  • Reproductive Biology
  • Molecular Andrology
  • Spermatozoa Function

Background:

  • Phospholipase C zeta (PLCζ) plays a crucial role in oocyte activation and fertilization.
  • Deficiency or dysfunction of PLCζ has been implicated in cases of failed fertilization after intracytoplasmic sperm injection (ICSI).
  • Understanding the factors contributing to PLCζ alterations is vital for diagnosing and treating male infertility.

Purpose of the Study:

  • To characterize phospholipase C zeta (PLCζ) deficiency in infertile men experiencing fertilization failure post-ICSI.
  • To investigate the relationship between sperm DNA fragmentation, chromatin decondensation, and PLCζ levels and localization.

Main Methods:

  • Semen analysis (concentration, motility, morphology) in 135 men (65 fertile, 70 infertile).
  • Assessment of PLCζ protein levels and localization via immunofluorescence and quantitative methods.
  • Evaluation of sperm DNA fragmentation (TUNEL assay) and chromatin decondensation (aniline blue staining).

Main Results:

  • Infertile patients showed significantly lower proportions of spermatozoa with PLCζ (18.41%) compared to fertile controls (67.31%).
  • Reduced PLCζ protein levels and altered localization patterns (acrosomal, equatorial) were observed in infertile men.
  • Significant correlations were found between sperm parameters, PLCζ levels, DNA fragmentation, and chromatin decondensation, particularly between PLCζ presence and DNA integrity (p < 0.001).

Conclusions:

  • Sperm DNA fragmentation and chromatin decondensation are associated with altered PLCζ localization and reduced protein levels.
  • These PLCζ alterations may be a contributing factor to total fertilization failure in infertile men.
  • The findings highlight the importance of evaluating PLCζ in cases of recurrent ICSI failure.
Keywords:
DNA fragmentationPLCζchromatin decondensationfertilization failuresemen parameters

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