Protamine 2 precursors (Pre-P2), protamine 1 to protamine 2 ratio (P1/P2), and assisted reproduction outcome

Mateo, Sara de; Gázquez, Cristina; Guimerà, M.; Balasch, Juan; Meistrich, Marvin L.; Ballescà, Josep Lluís; Oliva, Rafael

doi:10.1016/j.fertnstert.2007.12.047

Cited by 94 publications

(76 citation statements)

References 48 publications

(89 reference statements)

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“…A total of nine studies with 633 patients and 463 controls in the first part, which fulfilled all of the inclusion criteria, were considered for the analysis. Five of the studies were prospective (de Mateo et al, 2009;Garcia-Peiro et al, 2011;Rogenhofer et al, 2013;Ni et al, 2014;Savadi-Shiraz et al, 2015) and four were retrospective (Mengual et al, 2003;Aoki et al, 2005aAoki et al, , 2006aSteger et al, 2008). Four studies used real-time RT-qPCR (mRNA) (Steger et al, 2008;Rogenhofer et al, 2013;Ni et al, 2014;Savadi-Shiraz et al, 2015) and five studies employed PAGE (protein) (Mengual et al, 2003;Aoki et al, 2005aAoki et al, , 2006ade Mateo et al, 2009;Garcia-Peiro et al, 2011) to calculate the protamine ratio.…”

Section: Study Design Characteristicsmentioning

confidence: 99%

“…Four studies used real-time RT-qPCR (mRNA) (Steger et al, 2008;Rogenhofer et al, 2013;Ni et al, 2014;Savadi-Shiraz et al, 2015) and five studies employed PAGE (protein) (Mengual et al, 2003;Aoki et al, 2005aAoki et al, , 2006ade Mateo et al, 2009;Garcia-Peiro et al, 2011) to calculate the protamine ratio. When comparing the differences in the protamine ratio between experimental and control groups, two studies compared normozoospermic healthy donors with subfertile patients (Steger et al, 2008;Savadi-Shiraz et al, 2015), five studies compared proven fertile donors with subfertile patients (Mengual et al, 2003;Aoki et al, 2005aAoki et al, , 2006ade Mateo et al, 2009;Garcia-Peiro et al, 2011), one study compared groups of men contributing to successful fertilization with those involved in fertilization failure after IVF and ICSI treatment (Rogenhofer et al, 2013), and one study compared spontaneous pregnant couples with non-pregnant couples (Ni et al, 2014). In the second part, the total number of studies included in the review was 12 comprising of 845 participants.…”

Section: Study Design Characteristicsmentioning

confidence: 99%

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The impact of sperm protamine deficiency and sperm DNA damage on human male fertility: a systematic review and meta-analysis

et al. 2016

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SUMMARYExisting literature suggests evidence that protamine deficiency is related to DNA damage and male fertility. In this meta-analysis, we analyzed the relationship between the ratio of protamine-1 and protamine-2 with male fertility and the association of protamine deficiency with sperm DNA damage. Quality of available cohort studies was evaluated using the Newcastle-Ottawa Scale checklist. Summary effect estimates with 95% confidence intervals (CI) were derived using a random effects model. The effect of the protamine ratio on male fertility was analyzed in nine studies demonstrating a significantly higher value of the protamine ratio in subfertile men (n = 633) when compared with controls (n = 453, SMD = 0.46, 95% CI 0.25-0.66, Z = 4.42, p < 0.00001). Both protamine mRNA (SMD = 0.45, 95% CI 0.11-0.79, Z = 2.63, p = 0.009) and protein ratio (SMD = 0.46, 95% CI 0.25-0.68, Z = 4.22, p < 0.0001) showed significantly increased values in subfertile patients. The association between protamine deficiency and DNA damage was analyzed in 12 studies (n = 845) exhibiting a combined overall correlation coefficient (COR) of 0.53 (95% CI 0.28-0.71, Z = 3.87, p < 0.001). Protamine deficiency measured by CMA3 staining was significantly associated with sperm DNA damage (COR = 0.71, 95% CI 0.48-0.85, Z = 4.87, p < 0.001), whereas the P1/P2 ratio was not (COR = 0.17, 95% CI À0.16 to 0.46, Z = 0.99, p = 0.33). It is concluded that the protamine ratio represents a suitable biomarker for the assessment of sperm quality and protamine deficiency is closely related with sperm DNA damage.

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Section: Study Design Characteristicsmentioning

confidence: 99%

Section: Study Design Characteristicsmentioning

confidence: 99%

The impact of sperm protamine deficiency and sperm DNA damage on human male fertility: a systematic review and meta-analysis

et al. 2016

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“…Erroneous processing of protamine transcripts leads to increase in the production of immature P2 precursors associated with subfertility [84,85]. Despite controversial publications, deviations in protamine ratio might be associated with various phenotypic features including decreased sperm counts and function and poor embryonic quality [86,87].…”

Section: Role Of Protamination In Male Infertilitymentioning

confidence: 99%

The role of epigenetics in idiopathic male infertility

Güneş

Arslan

Hekim

et al. 2016

J Assist Reprod Genet

106

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Infertility is a complex disorder with multiple genetic and environmental causes. Although some specific mutations have been identified, other factors responsible for sperm defects remain largely unknown. Despite considerable efforts to identify the pathophysiology of the disease, we cannot explain the underlying mechanisms of approximately half of infertility cases. This study reviews current data on epigenetic regulation and idiopathic male infertility. Recent data have shown an association between epigenetic modifications and idiopathic infertility. In this regard, epigenetics has emerged as one of the promising research areas in understanding male infertility. Many studies have indicated that epigenetic modifications, including DNA methylation in imprinted and developmental genes, histone tail modifications and short non-coding RNAs in spermatozoa may have a role in idiopathic male infertility.

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“…(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%

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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Protamine 2 precursors (Pre-P2), protamine 1 to protamine 2 ratio (P1/P2), and assisted reproduction outcome

Cited by 94 publications

References 48 publications

The impact of sperm protamine deficiency and sperm DNA damage on human male fertility: a systematic review and meta-analysis

The impact of sperm protamine deficiency and sperm DNA damage on human male fertility: a systematic review and meta-analysis

The role of epigenetics in idiopathic male infertility

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

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