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Published on: March 1, 2019
Decreased protamine-1 transcript levels in testes from infertile men
Klaus Steger1, Ludger Fink, Klaus Failing
1Institute of Veterinary Anatomy, Histology and Embryology, University of Giessen, Germany. Klaus.Steger@vetmed.uni-giessen.de
Abstract:
Infertile men exhibit an aberrant protamine-1 (Prm1) to protamine-2 (Prm2) ratio at both the mRNA and protein level. We therefore investigated whether male infertility could be related to the amount of Prm1 and Prm2 mRNA by applying real time quantitative PCR following RNA extraction from routinely Bouin-fixed and paraffin-embedded testicular biopsies. Samples (n = 51) were normalized to the same amount and similar size of tissue sections. The threshold cycle (C(T)) representing a measure of the initial number of mRNA copies was significantly (P < 0.001) higher for Prm1, but not Prm2, and thus the amount of Prm1 mRNA was lower in men with at least qualitatively normal spermatogenesis (Prm1: 29.88 +/- 2.99; Prm2: 34.28 +/- 2.26) and impaired spermatogenesis (Prm1: 31.89 +/- 2.54; Prm2: 35.59 +/- 2.09) compared with men with obstructive azoospermia and quantitatively normal spermatogenesis (Prm1: 29.04 +/- 1.02; Prm2: 34.91 +/- 1.40). In addition, the Prm1 - Prm2 C(T) difference (deltaC(T)) was significantly (P < 0.001) decreased in these two groups. A negative correlation (r = -0.504; P < 0.001) was demonstrated between the score for efficiency of spermatogenesis and the C(T) for Prm1. These data suggest that the decreasing amount of Prm1 and, as a consequence, the aberrant Prm1:Prm2 mRNA ratio plays an important role for male infertility and may serve as a possible predictive factor for the outcome of ICSI.
Insights
Male infertility is linked to a lower amount of protamine-1 (Prm1) mRNA, disrupting the Prm1 to protamine-2 (Prm2) ratio. This finding may help predict intracytoplasmic sperm injection (ICSI) success.
Area of Science:
- Reproductive Biology
- Molecular Genetics
- Andrology
Background:
- Infertile men often display an abnormal protamine-1 (Prm1) to protamine-2 (Prm2) ratio at both mRNA and protein levels.
- This aberrant ratio is a potential indicator of impaired male fertility.
Purpose of the Study:
- To investigate the relationship between the quantity of Prm1 and Prm2 mRNA and male infertility.
- To determine if Prm1 and Prm2 mRNA levels can predict the success of intracytoplasmic sperm injection (ICSI).
Main Methods:
- Real-time quantitative PCR was used to measure Prm1 and Prm2 mRNA levels.
- RNA was extracted from routinely Bouin-fixed and paraffin-embedded testicular biopsies (n=51).
- Samples were normalized for tissue section size and quantity.
Main Results:
- The amount of Prm1 mRNA was significantly lower in men with impaired spermatogenesis compared to those with obstructive azoospermia and normal spermatogenesis.
- A significantly decreased Prm1 to Prm2 mRNA threshold cycle difference (deltaC(T)) was observed in infertile groups.
- A negative correlation was found between spermatogenesis efficiency score and Prm1 mRNA levels.
Conclusions:
- A decreasing amount of Prm1 mRNA and the resulting aberrant Prm1:Prm2 ratio are significant factors in male infertility.
- Prm1 mRNA levels may serve as a predictive biomarker for ICSI outcomes in infertile men.
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