Effects of failed oocyte activation and sperm protamine deficiency on fertilization post-ICSI

Abstract

Sperm premature chromosomal condensation (PCC) has been associated with failed fertilization. Previous studies suggest that protamine deficiency or failed oocyte activation may make spermatozoa prone to PCC. However, it is not clear which of these two factors has a more profound effect on fertilization failure. In order to distinguish between these two phenomena, oocytes that failed to fertilize after intracytoplasmic sperm injection (ICSI) were artificially activated and the association between protamine deficiency and PCC was evaluated in the remaining oocytes that failed to fertilize. The results of this study reveal that after artificial activation, fertilization rate post-ICSI increased from 59.95 to 87.7% and PCC spermatozoa appeared to be present in over 50% of the remaining oocytes that failed to fertilize. The percentage of sperm PCC was significantly higher in protamine deficient samples, thus suggesting that after failed oocyte activation, sperm PCC induced by protamine deficiency may be considered as an alternative cause of failed fertilization post-ICSI. Furthermore, the results of this study did not show any correlation between pronuclei size asynchrony and protamine deficiency.

CASA derived human sperm abnormalities: correlation with chromatin packing and DNA fragmentation

“…In the present study a significant positive correlation was observed between CMA3 positive and abnormal groups when compared with normal group. These findings are consistent with earlier works done by several authors [53][54][55][56].…”

“…Similarly, several studies have confirmed that poor chromatin packing may lead to sperm decondensation failures post ICSI which affects the fertilization process [50][51][52]. Furthermore, several studies have also demonstrated a strong correlation between abnormal protamination and sperm DNA fragmentation [53][54][55]. Protamine confers a high level compactness to sperm nucleus during spermatogenesis and abnormal protamination may result in increased susceptibility of the paternal genome to physical and chemical damage leading to DNA fragmentation.…”

Both protamine-1 to protamine-2 mRNA ratio and Bcl2 mRNA content in testicular spermatids and ejaculated spermatozoa discriminate between fertile and infertile men

“…A similar phenomenon has been described in infertile patients (Tesarik et al, 2004). There is evidence that links high DNA fragmentation indexes with diminished sperm DNA integrity (Aoki et al, 2005), decreased protamine content (Nasr-Esfahani et al, 2005) and lower IVF and ICSI rates (Evenson and Wixon, 2006). Although Oosterhuis et al (2000)reported DNA strand breaks and apoptotic marker annexin V in ejaculated Figure 2: (a) Correlation between the protamine-1 to protamine-2 log-ratio (DC t (P2 -P1)) and normalized Bcl2 log-concentration (DC t (P2 -Bcl2)) in testicular biopsies (R 2 ¼ 0.3320, P ¼ 0.0250).…”

ART failure: oocyte contributions to unsuccessful fertilization

“…The concentration of oocyte glutathione increases during maturation and is required for sperm decondensation and formation of the male pronucleus (Perreault et al, 1988;Sutovsky and Schatten, 1997). Furthermore, premature sperm chromatin condensation (PCC) is a prevalent etiology of fertilization failure in human ART and PCC is dependent upon the maturity of the oocyte (Calafell et al, 1991), possibly as the result of inability to complete oocyte activation (Nasr-Esfahani et al, 2007). Capability of oocytes to replace sperm protamines with histones is gained during maturation.…”