Characterization of two heterozygous mutations of the oocyte activation factor phospholipase C zeta (PLCζ) from an infertile man by use of minisequencing of individual sperm and expression in somatic cells

Protein phospholipase C Zeta1 expression in patients with failed ICSI but with normal sperm parameters

“…In one case, after careful analysis of the PLCZ1 gene sequence, point mutations that undermined the activity of the enzyme were found in the catalytic region of PLCZ1, providing a molecular explanation for the lack of egg activation and infertility observed in the patient [31,15]. Here, we found 3 patients that despite displaying normal gross sperm morphology and SA parameters failed or had low fertilization after ICSI.…”

Single Ca2+ transients vs oscillatory Ca2+ signaling for assisted oocyte activation: limitations and benefits

“…Of note, low and high levels of PLCζ were associated with low oocyte activation potential and embryo development arrest, respectively (Yu et al 2008). Moreover, the direct injection of recombinant human PLCζ at a concentration of 80 fg allowed mouse blastocyst formation in a proposed prototype for male infertility based on failed fertilization observed after the injection of PLCζ cRNA encoding known point mutations (Kashir et al 2012, Nomikos et al 2013. A definite protocol describing whether exogenous PLCζ would induce a real benefit for human oocyte activation and embryo development has not been yet established.…”

“…MOAT groups range from low-to-high activation potential. MOAT group 1 (0-20% of 2-cell embryos 24 h after ICSI) includes patients with a sperm-related activation deficiency, such as cases with globozoospermia (Heytens et al 2010) or carriers of mutations in the PLCζ gene (Heytens et al 2009, Kashir et al 2012. MOAT 2 (21-84%) includes patients showing diminished activation capacity and MOAT 3 (>85%) includes patients indicating a normal activation capacity, comparable to a positive control and consequently pointing more to an oocyterelated activation deficiency (Heindryckx et al 2005).…”

Total levels, localization patterns, and proportions of sperm exhibiting phospholipase C zeta are significantly correlated with fertilization rates after intracytoplasmic sperm injection

“…Therefore, development of a novel or additional biological tool is fundamental to being able to predict the fertilizing ability of a given sperm sample, as this study sought to do. Since the discovery of the sperm-soluble oocyte activation factor, PLCz (20), a strong body of both biochemical and clinical evidence has steadily accumulated in support of the fundamental role of PLCz as a universal trigger for oocyte activation in mammalian (19,20,24,40,41) and nonmammalian species (42)(43)(44)(45). Despite this evidence, recent studies suggest that a postacrosomal sperm protein found in the perinuclear theca, and known as PAWP (postacrosomal WW binding protein), elicits calcium oscillations similar to those seen during fertilization in mammalian (46,47) and nonmammalian oocytes (48).…”