Phospholipase C zeta parameters in sperm from polymorphic teratozoospermic men

Azad, Nahid; Nazarian, Hamid; Novin, Marefat Ghaffari; Farahani, Reza Masteri; Piryaei, Abbas; Heidari, Mohammad Hassan

doi:10.1016/j.aanat.2017.09.007

Cited by 16 publications

(14 citation statements)

References 35 publications

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“…This suggests that PLCζ analysis may be helpful with predicting the chances of fertilization success, and that combining PLCζ analysis results and the PLCζ categorization may better predict clinical pregnancy success. Interestingly, two of ICSI-AOA patients had normal semen parameters upon undergoing ICSI-AOA, suggesting that PLCζ analysis may complement routine semen analysis and target AOA-eligible patients with normozoospermia, not only teratozoospermia (52). The present study did not correlate semen parameters (Supplementary table 3) with PLCζ expression, as previous evidence has shown that PLCζ characteristics significantly correlate with semen quality (sperm concentration, motility and morphology).…”

Section: Discussionsupporting

confidence: 44%

Use of phospholipase C zeta analysis to identify candidates for artificial oocyte activation: a case series of clinical pregnancies and a proposed algorithm for patient management

Meng

Melo

Jones

et al. 2020

Fertility and Sterility

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Objective: To investigate the applicability of PLCζ analysis in assisting the clinical decisionmaking process when considering artificial oocyte activation (AOA) for infertile males in assisted reproductive technology (ART). Design:To screen 46 males (43 infertile/13 fertile) using our PLCζ assay.Setting: Fertility unit/university laboratory.Patients: Infertile males with (1) abnormal sperm morphology, (2) total fertilization failure, low fertilization rate (<50%), or repeated fertilization failure in ART. Intervention(s):We analysed PLCζ levels in sperm from fertile and infertile males. Eligible patients subsequently underwent ICSI/AOA with calcimycin (GM508). Main Outcome Measure(s): PLCζ localization, level and the proportion of sperm expressingPLCζ. Thresholds of PLCζ-deficiency, fertilization rates, pregnancy rates and live birth rates of AOA and non-AOA cycles.Results: Compared with 13 controls, 34 of the 43 infertile males had significantly lower levels of PLCζ and/or a significantly lower proportion of sperm exhibiting PLCζ. Of these 34 patients, 15 showed a significant PLCζ reduction in both parameters, which we termed 'PLCζ deficiency'. Five PLCζ-deficient patients opted for AOA; all 5 achieved fertilization and 4 achieved clinical pregnancies and live births. Fertilization rate improved significantly from 18.6% (intracytoplasmic sperm injection, ICSI) to 56.8% (ICSI/AOA) (p<0.001). The clinical pregnancy rate and live birth rate with AOA were both 40% per initiated cycle. Youden index analysis revealed that the cut-offs below which infertile males were likely to benefit from AOA were 71% for the proportion of sperm expressing PLCζ and 15.57 arbitrary units for mean PLCζ level. Conclusion:PLCζ analysis is a useful diagnostic tool to determine patient eligibility for subsequent AOA treatment.

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Section: Discussionsupporting

confidence: 44%

Use of phospholipase C zeta analysis to identify candidates for artificial oocyte activation: a case series of clinical pregnancies and a proposed algorithm for patient management

Meng

Melo

Jones

et al. 2020

Fertility and Sterility

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“…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.…”

Section: Successful Fertilisation Is Associated With Higher Total Lmentioning

confidence: 99%

“…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 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Background Oocyte activation is driven by intracellular calcium (Ca2+) oscillations induced by sperm‐specific PLCζ, abrogation of which causes oocyte activation deficiency in humans. Clinical PLCζ investigations have been limited to severe male infertility conditions, while PLCζ levels and localisation patterns have yet to be associated with general sperm viability. Materials and Methods PLCζ profiles were examined within a general population of males attending a fertility clinic (65 patients; aged 29‐53), examining PLCζ throughout various fractions of sperm viability. Male recruitment criteria required a minimum sperm count of 5 × 106 spermatozoa/mL, while all female patients included in this study yielded at least five oocytes for treatment. Sperm count, motility and semen volume were recorded according to standard WHO reference guidelines and correlated with PLCζ profiles examined via immunoblotting and immunofluorescence. Appropriate fertility treatments were performed following routine clinical standard operating protocols, and fertilisation success determined by successful observation of second polar body extrusion. Results and Discussion Four distinct PLCζ patterns were observed at the equatorial, acrosomal + equatorial regions of the sperm head, alongside a dispersed pattern, and a population of spermatozoa without any PLCζ. Acrosomal + equatorial PLCζ correlated most to sperm health, while dispersed PLCζ correlated to decreased sperm viability. Total levels of PLCζ exhibited significant correlations with sperm parameters. PLCζ variance corresponded to reduced sperm health, potentially underlying cases of male sub‐fertility and increasing male age. Finally, significantly higher levels of PLCζ were exhibited by cases of fertilisation success, alongside higher proportions of Ac + Eq, and lower levels of dispersed PLCζ. Conclusions PLCζ potentially represents a biomarker of sperm health, and fertilisation capacity in general cases of patients seeking fertility treatment, and not just cases of repeated fertilisation. Further focused investigations are required with larger cohorts to examine the full clinical potential of PLCζ.

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“…It has been shown that PLCZ1 is heat-sensitive; therefore, this condition may disrupt the final translation of the protein ( Sanusi et al 2015 ). Accordingly, sperm from infertile males with teratozoospermia (abnormal head morphology) have previously been demonstrated to exhibit abnormal localization or the absence of PLCZ1 but showed a variance in PLCZ1 expression in comparison to controls ( Azad et al 2018 ). However, in another report, involving patients with asthenoteratozoospermia, in which motility and morphology are abnormal, showed no difference in PLCZ1 localization ( Rahimizadeh et al 2020 ).…”

Section: What Is Known About the Localization Patterns And Expression...mentioning

confidence: 99%

SPERM FACTORS AND EGG ACTIVATION: Phospholipase C zeta (PLCZ1) and the clinical diagnosis of oocyte activation deficiency

2022

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Oocyte activation deficiency (OAD) remains the predominant cause of total/low fertilization rate in assisted reproductive technology (ART). Phospholipase C zeta (PLCζ) is the dominant sperm-specific factor responsible for triggering oocyte activation in mammals. OAD has been linked to numerous PLCζ abnormalities in patients experiencing failed in-vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI) cycles. While significant efforts have enhanced our understanding of the clinical relevance of PLCζ, and the potential effects of genetic variants upon functionality, our ability to apply PLCζ in a diagnostic or therapeutic role remains limited. Artificial oocyte activation (AOA) is the only option for patients experiencing OAD but lacks a reliable diagnostic approach. Immunofluorescence analysis has revealed that the levels and localization patterns of PLCζ within sperm can help us to indirectly diagnose a patient’s ability to induce oocyte activation. Screening of the gene encoding PLCζ protein is also critical if we are to fully determine the extent by which genetic factors might play a role in the aberrant expression and/or localization patterns observed in infertile patients. Collectively, these findings highlight the clinical potential of PLCζ, both as a prognostic indicator of OAD, and eventually as a therapeutic agent. In this review, we focus on our understanding of the association between OAD and PLCζ by discussing the localization and expression of this key protein in human sperm, the potential genetic causes of OAD, and the diagnostic tools that are currently available to us to identify PLCζ deficiency and select patients that would benefit from targeted therapy.

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Phospholipase C zeta parameters in sperm from polymorphic teratozoospermic men

Cited by 16 publications

References 35 publications

Use of phospholipase C zeta analysis to identify candidates for artificial oocyte activation: a case series of clinical pregnancies and a proposed algorithm for patient management

Use of phospholipase C zeta analysis to identify candidates for artificial oocyte activation: a case series of clinical pregnancies and a proposed algorithm for patient management

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

SPERM FACTORS AND EGG ACTIVATION: Phospholipase C zeta (PLCZ1) and the clinical diagnosis of oocyte activation deficiency

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