Relationship between phospholipase C-zeta, semen parameters, and chromatin status

Abstract

The need for additional tests to complement basic sperm analysis in clinics is well appreciated. In this regard, a number of tests such as sperm DNA integrity test as a tool in diagnosis and treatment of infertility are suggested. But recent studies have focused on main sperm factors involved in oocyte activation such as phospholipase C-zeta (PLCζ) that initiate intracellular Ca signaling and embryogenesis. Therefore, this study aimed to investigate the relationship between PLCζ, basic semen parameters, sperm DNA fragmentation (SDF), and protamine deficiency in men with normal (n=32) and abnormal (n=23) semen parameters. Unlike SDF and protamine deficiency, as negative factors related to fertility, the mean value of PLCζ as positive factor related to infertility was significantly lower in men with abnormal semen parameters compared to men with normal semen parameters. Significant correlations were also observed between sperm concentration, motility, and abnormal morphology with the percentage of PLCζ positive spermatozoa. In addition, logistic regression analysis revealed that sperm morphology is more predictive than sperm motility and concentration for PLCζ presence. In addition, a statistically significant negative relationship was observed between the percentage of PLCζ positive spermatozoa and SDF. These findings suggested during ICSI, selection of sperm based on morphology has a profound effect on its ability to induce oocyte activation based on the likelihood of PLCζ expression. Therefore, assessment of PLCζ as an index for fertilization potential of a semen sample in men with severe teratozoospermia may define individuals who are candidates for artificial oocyte activation (AOA) and may avoid failed fertilization post ICSI.

Relationship between sperm telomere length and sperm quality in infertile men

“…For each sample, at least 500 spermatozoa were counted using a fluorescence microscope (BX51). Spermatozoa with green nuclei were considered as DNA fragmentation (Tavalaee et al, ).…”

“…According to literature, DNA integrity can be affected by a series of exogenous and endogenous factors during production of spermatozoon in the testicles and/or passage of spermatozoon in the epididymis (Moustafa et al, ; Ramos, de Boer, Meuleman, Braat, & Wetzels, ). Excessive production of oxidative stress, apoptosis, and abnormal chromatin packaging or protamine deficiency in spermatozoon along with reduced antioxidant capacity are considered as the most important endogenous factors that accounts for reduced DNA integrity (Darmishonnejad, Tavalaee, Tanhaei, Nasr‐Esfahania, & Izadi, ; Moskovtsev, Willis, White, & Mullen, ; Nasr‐Esfahani, Razavi, Mardani, Shirazi, & Javanmardi, ; Nasr‐Esfahani, Razavi, & Tavalaee, ; Sadeghi et al, ; Tavalaee, Kiani‐Esfahani, & Nasr‐Esfahani, ).…”

Reduced sperm telomere length in individuals with varicocele is associated with reduced genomic integrity

“…DNA fragmentation was carried out according to Tavalaee et al . using a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay 46 . Briefly, semen samples were washed with PBS and fixed in 4% methanol-free formaldehyde on slides for 30 min.…”

Phospholipase C zeta profiles are indicative of optimal sperm parameters and fertilisation success in patients undergoing fertility treatment

“…This is particularly concerning for PLCζ localisation patterns, where a dominant motif has yet to be isolated in relation to sperm health. To this degree, previous attempts to examine PLCζ profiles in human spermatozoa in relation to male conditions [24][25][26]28,[39][40][41][42] have been viewed with caution due to antibody specificity and protocol sensitivity. 30,43,44 Predictably, such shortcomings have led to conflicting results between the association of specific PLCζ localisation patterns and quantification levels.…”

“…13 Mutations identified in the PLCζ gene of such patients resulted in predicted modifications of the enzyme fold, abrogating PLCζ activity and/or levels within the spermatozoa. [14][15][16][17][18][19][20][21] Indeed, reduced/absent levels of PLCζ are a hallmark of OAD spermatozoa, 1,13,14,18,22 with PLCζ deficiencies associated with multiple male-specific conditions including abnormal sperm morphology, 1,14,18,[23][24][25][26] sperm DNA fragmentation and oxidation 27,28 and abnormal pregnancies. 29 Thus, immunological analysis of PLCζ in human spermatozoa could be a powerful diagnostic approach 13,14,19,23,30,31 [for a detailed review, see Kashir et al 1 ].…”