Sperm protamine 1/protamine 2 ratios are related to in vitro fertilization pregnancy rates and predictive of fertilization ability

Aoki, Vincent W.; Liu, Lihua; Jones, Kirtly Parker; Hatasaka, Harry H.; Gibson, Mark; Peterson, C. Matthew; Carrell, Douglas T.

doi:10.1016/j.fertnstert.2006.04.024

Cited by 165 publications

(119 citation statements)

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“…It has previously been shown that generally these patients have lower sperm concentrations and motility than fertile men, and a higher frequency of abnormal sperm morphology and DNA damage than fertile controls. (14)(15)(16)(17)(19)(20)(21) Furthermore, lower pregnancy rates have also been reported in patients with abnormal protamine replacement, even when intracytoplasmic sperm injection is performed. 15,17,18,21 Whether aberrant protamination is the cause of infertility or simply an indication of other abnormalities during spermatogenesis is not known.…”

Section: Discussionmentioning

confidence: 99%

“…(14)(15)(16)(17)(19)(20)(21) Furthermore, lower pregnancy rates have also been reported in patients with abnormal protamine replacement, even when intracytoplasmic sperm injection is performed. 15,17,18,21 Whether aberrant protamination is the cause of infertility or simply an indication of other abnormalities during spermatogenesis is not known. Additionally, the possible causes of abnormal embryogenesis resulting in lower in vitro fertilization pregnancy rates have not been evaluated beyond the possible effects of elevated DNA damage.…”

Section: Discussionmentioning

confidence: 99%

“…11,12,14,15 Several studies have reported that diminished sperm quality, increased DNA fragmentation and reduced pregnancy rates are associated with an altered protamine ratio. [14][15][16][17][18][19][20][21] However, the mechanism to explain how abnormal protamination results in altered semen quality and reduced pregnancy rates is not known.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of the methylation pattern of six gene promoters in sperm of men with abnormal protamination

Nánássy

Carrell²

2011

Asian J Androl

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It has recently been shown that alteration of the methylation pattern of imprinted genes is associated with different types of male infertility. The objective of our study was to investigate the methylation pattern of selected gene promoters in sperm of patients with abnormal protamine replacement. The promoters of OCT4, SOX2, NANOG, HOXC11, miR-17 and CREM were analyzed using bisulfite sequencing and the percentage of DNA methylation was compared between patients with an abnormal protamine 1/protamine 2 (P1/ P2) ratio and normozoospermic controls. No significant quantitative differences were found between groups of patients with either an abnormally high or low P1/P2 ratio compared to normal controls. However, two individual samples from infertile subjects (2/20, 10%) showed an altered methylation pattern for the CREM gene promoter that was not found in control samples. These two samples had a significantly higher (P,0.05) promoter methylation (5.58 and 4.23%, respectively) compared to the control group (0.46%). In conclusion, in our pilot study, extreme methylations defects were not seen broadly in severely infertile men. However, two patients exhibited altered methylation of the CREM gene, which may be either causative or a result of abnormal protmaine replacement.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Analysis of the methylation pattern of six gene promoters in sperm of men with abnormal protamination

Nánássy

Carrell²

2011

Asian J Androl

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“…51 In humans, the proportion of protamine 1(P1) to protamine 2 (P2) is approximately 1:1, and changes to this ratio are associated with altered sperm quality and decreased embryo quality and IVF outcomes. 53 Diagnostic tests now under development seek to determine the quality of the sperm decondensation process and its role in male infertility. 53 Human sperm heads can be decondensed in vitro using either oocytes from animals (e.g., frog) or with detergents.…”

Section: Chromatin Condensation and Sperm Epigeneticsmentioning

confidence: 99%

“…53 Diagnostic tests now under development seek to determine the quality of the sperm decondensation process and its role in male infertility. 53 Human sperm heads can be decondensed in vitro using either oocytes from animals (e.g., frog) or with detergents. However, precise determination of the degree of sperm head decondensation is time-consuming and time sensitive, because the process is dynamic.…”

Section: Chromatin Condensation and Sperm Epigeneticsmentioning

confidence: 99%

An Assessment of New Sperm Tests for Male Infertility

Natali

Turek

2011

Urology

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The routine semen analysis, although used for more than 50 years, fails to accurately distinguish between fertile and infertile men. As a consequence, many tests of sperm function (TSF) have been developed. This review discusses both older and newer diagnostic TSF. It outlines the principles underlying each assay and reviews aggregate clinical data to determine its current relevance and utility. It concludes that the relevance of many older TSF is questionable, with the wide acceptance of intracytoplasmic sperm injection (ICSI). Newer TSF have the potential to deliver more clinically relevant information but require more extensive study to better understand their predictive role in the ICSI era. UROLOGY 77: 1027-1034, 2011. © 2011 Elsevier Inc. All rights reserved.I n addition to the medical history and physical examination, the conventional semen analysis has been an essential laboratory test for the evaluation of male fertility for at least 50 years. However, the idea that fertility can be defined by threshold values of semen parameters is a concept that is fundamentally flawed. 1 Although not a true measure of fertility, the semen analysis, if abnormal, suggests that the probability of achieving fertility is lower than normal. 2 Because of biological variability, two semen analyses are generally needed, performed with two to three days of sexual abstinence and evaluated in a standardized fashion. 2 Recognized normal values for semen parameters are given in Table 1 in agreement with the latest recommendations by the World Health Organization (WHO). 2 Traditionally, (except for the latest WHO recommendations), these references are derived by expert consensus and not by prospective clinical trials and thus their true relationship to male fertility is unclear. In addition, the definition of what constitutes "normal" semen parameters is constantly challenged. A meta-analysis of 29 US studies of semen quality from 9612 fertile, or presumably fertile, men suggested that a sperm concentration of 98 million/mL is normal. 3 Although sperm motility is considered the "best" predictor of fertility, normal sperm motility ranges from 53% to 62%. 4 Thus, simply deriving "normal" semen parameters has been a prohibitively lengthy and inconclusive process to date.Finally, other biological variables affect the clinical utility of the semen analysis. In addition to wide intraindividual variation, seasonal 5 and geographic variation 4 further complicate the performance of the semen analysis as a fertility measure. As examples, within-subject, interejaculate coefficients of variation for sperm concentration and motility are estimated at 44.7% and 15% in one study. 1 Thus, even with excellent quality control, wide biological variation in semen quality profoundly challenges the notion that the conventional semen analysis can accurately assess male fertility. OLDER ADJUNCTIVE SPERM TESTSBecause of the need to more precisely characterize normal fertile semen, adjunctive semen testing has become popular (Figure 1). The concept behind de...

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Coprs inactivation leads to a derepression of LINE1 transposons in spermatocytes

et al. 2018

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Repression of retrotransposons is essential for genome integrity during germ cell development and is tightly controlled through epigenetic mechanisms. In primordial germ cells, protein arginine N ‐methyltransferase (Prmt5) is involved in retrotransposon repression by methylating Piwi proteins, which is part of the pi RNA pathway. Here, we show that in mice, genetic inactivation of coprs (which is highly expressed in testis and encodes a histone‐binding protein required for the targeting of Prmt5 activity) affects the maturation of spermatogonia to spermatids. Mass spectrometry analysis revealed the presence of Miwi in testis protein lysates immunoprecipitated with an anti‐Coprs antibody. The observed deregulation of Miwi and pachytene pre‐pi RNA s levels and the derepression of LINE 1 repetitive sequences observed in coprs ‐/‐ mice suggest that Coprs is implicated in genome surveillance mechanisms.

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Sperm protamine 1/protamine 2 ratios are related to in vitro fertilization pregnancy rates and predictive of fertilization ability

Cited by 165 publications

References 30 publications

Analysis of the methylation pattern of six gene promoters in sperm of men with abnormal protamination

Analysis of the methylation pattern of six gene promoters in sperm of men with abnormal protamination

An Assessment of New Sperm Tests for Male Infertility

Coprs inactivation leads to a derepression of LINE1 transposons in spermatocytes

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