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Published on: March 1, 2019
The alteration of PLCζ protein expression in unexplained infertile and asthenoteratozoospermic patients: A potential
Pegah Rahimizadeh1,2, Tohid Rezaei Topraggaleh3, Mohammad Hossein Nasr-Esfahani4
1Department of Molecular and Cellular Biology, Faculty of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran.
Abstract:
Failed oocyte activation has been observed in unexplained infertile (UI) and asthenoteratozoospermic (AT) men. The deficiency of phospholipase C-zeta (PLCζ) could be a possible reason for such failures and has not been studied yet. We investigated the expression and localization of PLCζ protein in the sperms of patients with UI and AT conditions. The relationships between PLCζ-related parameters with male age, sperm characteristics, DNA integrity, and cellular maturity were assessed. Semen samples were collected from fertile (n = 40), UI (n = 40), and AT (n = 40) men. Subsequently, semen analysis, DNA fragmentation, hyaluronic acid-binding ability, and PLCζ level along with its distribution were evaluated using computer-assisted sperm analyzer, sperm chromatin structure assay (SCSA), hyaluronic acid-binding assay (HBA), western blot analysis and immunofluorescence microscopy, respectively. Unlike SCSA, the values of HBA, and PLCζ expression were significantly reduced in UI and AT patients compared to fertile men, whereas no significant differences were observed among the experimental groups in terms of PLCζ localization patterns. The regression analysis also showed that HBA is the only variable associated with PLCζ levels. Furthermore, the correlation of male age with PLCζ localization in postacrosomal, equatorial, and acrosomal+postacrosomal+equatorial (A+PA+E) patterns, as well as the relation of normal morphology, with the (A+PA+E) pattern, remained in the regression model. Our findings indicated that reduced PLCζ level along with the increased DNA fragmentation and impaired maturation may be possible etiologies of decreased fertilization in the studied subjects.
Insights
Reduced phospholipase C-zeta (PLCζ) levels in sperm may explain failed oocyte activation in men with unexplained infertility (UI) and asthenoteratozoospermia (AT). Lower PLCζ and impaired sperm function were observed in these groups compared to fertile men.
Area of Science:
- Reproductive Biology
- Spermatozoa Function
- Infertility Research
Background:
- Failed oocyte activation is a concern in unexplained infertility (UI) and asthenoteratozoospermia (AT).
- Phospholipase C-zeta (PLCζ) deficiency is a potential, yet unstudied, cause of these activation failures.
Purpose of the Study:
- To investigate phospholipase C-zeta (PLCζ) protein expression and localization in sperm from UI and AT patients.
- To assess relationships between PLCζ parameters and male age, sperm characteristics, DNA integrity, and cellular maturity.
Main Methods:
- Semen samples from fertile (n=40), UI (n=40), and AT (n=40) men were analyzed.
- Evaluated sperm parameters, DNA fragmentation (SCSA), hyaluronic acid-binding ability (HBA), and PLCζ levels/localization (Western blot, immunofluorescence microscopy).
Main Results:
- UI and AT patients showed significantly reduced HBA and PLCζ expression compared to fertile men.
- No significant differences in PLCζ localization patterns were found across groups.
- HBA was the only variable significantly associated with PLCζ levels.
Conclusions:
- Reduced sperm PLCζ levels, increased DNA fragmentation, and impaired sperm maturation may contribute to decreased fertilization in UI and AT patients.
- PLCζ deficiency is a potential factor in failed oocyte activation in these infertile populations.
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