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Levels of the oocyte activator PLCζ may be linked to male age

Levels of the oocyte activator PLCζ may be linked to male age
Ramadan, WR; Jones, C; Kashir, J; Navarro, C; Díaz, JC; Coleman L; Coward, K
Introduction: The fundamental process of mammalian oocyte activation is regulated by the sperm-specific protein phospholipase C zeta (PLCζ). When introduced into the oocyte at gamete fusion, PLCζ initiates a series of signalling mechanisms which initiate oocyte activation and early embryogenesis. Absence, reduced levels, or abnormal localisation patterns of PLCζ in human sperm have been linked to certain types of infertility. Previous studies have identified multiple localisation patterns for PLCζ in mouse and human sperm, suggesting differential functional roles. In the mouse, PLCζ has been detected in both acrosomal and post-acrosomal regions. In human sperm, PLCζ has additionally been identified in the equatorial segment. Our previous work revealed notable variability in both total level and localisation pattern of PLCζ in human fertile controls, but whether these important parameters change with male age remains untested. Such a relationship may provide important clues as to whether oocyte activation capacity also varies with age. In the present study, we describe pilot data acquired from both a mouse model and fertile human donors.
Materials and methods: Quantitative immunofluorescent analysis of PLCζ protein in (1) swim-out sperm from the cauda epididymus [n=15] in mice aged 6, 16 and 32 weeks of age, and (2) sperm from fertile human donors [n=9] obtained with informed written consent and categorised into four age groups [20-25, 26-30, 31-35 and 36+ years of age]. Analysis involved 100 sperm per subject.
Results: Preliminary analyses from a laboratory mouse model indicated that the total level of PLCζ in the sperm head does not change significantly with male age. However, statistically significant changes in specific localisation pattern appear to occur with progressive male age (p<0.0004) with the post-acrosomal pattern becoming more dominant with advanced age. Conversely, we detected a significant reduction (p<0.0007) in the total level of PLCζ in human sperm with advancing age, but with no apparent relationship with localisation pattern.
Conclusions: Our findings are indicative of subtle species-specific relationships between PLCζ and advancing male age. Of particular note is the detection of a statistically significant reduction in the total level of PLCζ in human sperm with advancing male age. Whether this indicates an associated reduction in oocyte activation capacity remains to be tested. Current studies aim to both increase the number of human donors recruited and to incorporate physiological tests of oocyte activation ability.
Keywords: Sperm, oocyte activation, PLCζ, age, infertility



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