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Round spermatids from infertile men exhibit decreased protamine-1 and -2 mRNA
K Steger1, K Failing, T Klonisch
1Institute of Veterinary Anatomy, University of Giessen, Germany. Klaus.Steger@vetmed.uni-giessen.de
Abstract:
During spermiogenesis, histone-to-protamine exchange causes chromatin condensation. Spermatozoa from infertile men are known to exhibit an increased protamine-1 (PRM1) to protamine-2 (PRM2) protein ratio. Since patients undergoing testicular sperm extraction (TESE) followed by intracytoplasmic sperm injection (ICSI) reveal low fertilization rates, whether the outcome of ICSI could be related to the percentage of round spermatids expressing PRM1-mRNA and PRM2-mRNA was investigated. Applying in-situ hybridization, 55 testicular biopsies from men undergoing TESE/ICSI were investigated. The percentage of PRM1-mRNA and PRM2-mRNA positive spermatids was significantly (P < 0.0001) decreased in men with at least qualitatively normal spermatogenesis (PRM1-mRNA: 58.4 +/- 13.8%; PRM2-mRNA: 56.4 +/- 11.3%) and impaired spermatogenesis (PRM1-mRNA: 32.6 +/- 10.8%; PRM2-mRNA: 31.7 +/- 11.1%) compared with men with obstructive azoospermia and quantitatively normal spermatogenesis (PRM1-mRNA: 79.9 +/- 4.6%; PRM2-mRNA: 78.1 +/- 5.7%). A positive correlation (r(PRM1) = 0.733; r(PRM2) = 0.784; P < 0.001) was demonstrated between the score and the percentage of PRM1-mRNA and PRM2-mRNA positive spermatids. While successful fertilization was neither related to the score, nor to the percentage of PRM1-mRNA and PRM2-mRNA positive spermatids, a significant (P < 0.05) relationship was demonstrated between successful fertilization and the PRM1-mRNA to PRM2-mRNA ratio. Therefore, the PRM1-mRNA to PRM2-mRNA ratio in round spermatids may serve as a possible predictive factor for the outcome of ICSI.
Insights
The ratio of protamine-1 (PRM1) mRNA to protamine-2 (PRM2) mRNA in round spermatids may predict intracytoplasmic sperm injection (ICSI) success. Lower PRM1-mRNA and PRM2-mRNA expression in spermatids correlates with impaired spermatogenesis and impacts ICSI outcomes.
Area of Science:
- Reproductive Biology
- Spermatogenesis
- Male Infertility
Background:
- Spermiogenesis involves histone-to-protamine exchange for chromatin condensation.
- Infertile men often show an altered protamine-1 (PRM1) to protamine-2 (PRM2) protein ratio in spermatozoa.
- Low fertilization rates in testicular sperm extraction (TESE) followed by intracytoplasmic sperm injection (ICSI) necessitate investigation into predictive factors.
Purpose of the Study:
- To investigate the relationship between the expression of PRM1-mRNA and PRM2-mRNA in round spermatids and the success of ICSI.
- To determine if the percentage of spermatids expressing PRM1-mRNA and PRM2-mRNA can predict ICSI outcomes.
- To assess the PRM1-mRNA to PRM2-mRNA ratio as a potential biomarker for ICSI fertilization rates.
Main Methods:
- Analysis of 55 testicular biopsies from men undergoing TESE/ICSI.
- Application of in-situ hybridization to quantify PRM1-mRNA and PRM2-mRNA expression in round spermatids.
- Statistical analysis to correlate mRNA expression levels and ratios with spermatogenesis quality and ICSI fertilization rates.
Main Results:
- Significantly decreased percentages of PRM1-mRNA and PRM2-mRNA positive spermatids were observed in men with impaired spermatogenesis compared to those with normal spermatogenesis or obstructive azoospermia.
- A strong positive correlation was found between the percentage of PRM1-mRNA/PRM2-mRNA positive spermatids and a scoring system.
- Successful fertilization in ICSI was not related to the overall percentage of PRM1-mRNA or PRM2-mRNA positive spermatids, but was significantly associated with the PRM1-mRNA to PRM2-mRNA ratio.
Conclusions:
- The PRM1-mRNA to PRM2-mRNA ratio in round spermatids is a significant predictive factor for successful fertilization during ICSI.
- Quantifying PRM1-mRNA and PRM2-mRNA expression in spermatids could offer a valuable diagnostic tool for male infertility assessment.
- Further research into the role of protamine mRNA ratios may improve assisted reproductive technology outcomes.