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Expression of Glycogen synthase kinase 3-β (GSK3-β) gene in azoospermic men
Hamid Nazarian1, Marefat Ghaffari Novin2, Mohammad Reza Jalili1
1Department of Biology and Anatomical Sciences, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Background:
The Wnt/β- The Wnt/β-catenin signaling pathway is involved in many developmental processes in both fetal and adult life; its abnormalities can lead to disorders including several types of cancers and malfunction of specific cells and tissues in both animals and humans. Its role in reproductive processes has been proven.
Objective:
This study was designed to evaluate the expression of the key regulator of this signaling pathway GSK3-β and its presumed role in azoospermia.
Materials And Methods:
WNT3a protein concentration and GSK3-β gene expression levels were measured and compared between two groups of infertile men. The test groups consisted of 10 patients with obstructive and 10 non-obstructive azoospermia. The control group was selected among healthy men after vasectomies that were willing to conceive a child using a testicular biopsy technique. Samples were obtained by testicular biopsy and screened for the most common mutations (84, 86 and 255) in the SRY region before analyzing. GSK3-β gene expression was assessed quantitatively by real time-PCR.
Results:
The WNT3a protein concentration had no significant difference between the two test groups and controls. Expression of GSK3-β was down-regulated in non-obstructive azoospermia (3.10±0.19) compared with normal (7.12±0.39) and obstructive azoospermia (6.32±0.42) groups (p=0.001).
Conclusion:
Down-regulation of GSK-3β may cause to non-obstructive azoospermia. Regulation and modification of GSK-3β gene expression by drugs could be used as a therapeutic solution.
Insights
Glycogen synthase kinase 3 beta (GSK3-β) gene expression was significantly down-regulated in men with non-obstructive azoospermia. This finding suggests GSK3-β may play a role in male infertility and could be a therapeutic target.
Area of Science:
- Reproductive biology
- Molecular biology
- Genetics
Background:
- The Wnt/β-catenin signaling pathway regulates crucial developmental processes.
- Aberrations in this pathway are linked to cancers and tissue-specific malfunctions.
- Its established role in reproductive functions highlights its importance in male fertility.
Purpose of the Study:
- To investigate the expression of GSK3-β, a key regulator of Wnt/β-catenin signaling.
- To evaluate the potential role of GSK3-β in the pathogenesis of azoospermia.
Main Methods:
- Compared WNT3a protein and GSK3-β gene expression in infertile men (obstructive and non-obstructive azoospermia) and controls.
- Utilized testicular biopsy samples for analysis.
- Quantified GSK3-β gene expression using real-time PCR.
Main Results:
- WNT3a protein concentrations showed no significant differences across groups.
- GSK3-β gene expression was significantly lower in non-obstructive azoospermia patients compared to obstructive azoospermia and control groups (p=0.001).
Conclusions:
- Down-regulation of GSK3-β may contribute to non-obstructive azoospermia.
- Modulating GSK3-β gene expression presents a potential therapeutic strategy for male infertility.
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