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

BACKGROUND: Oocyte activation is driven by intracellular calcium (Ca(2+) ) oscillations induced by sperm specific PLCzeta, abrogation in which causes oocyte activation deficiency in humans. Clinical PLCzeta investigations have been limited to severe male infertility conditions, while PLCzeta levels and localisation patterns have yet to be associated with general sperm viability. MATERIALS AND METHODS: PLCzeta profiles were examined within a general population of males attending a fertility clinic (65 patients; aged 29-53), examining PLCzeta throughout various fractions of sperm viability. Male recruitment criteria required a minimum sperm count of 5x10(6) sperm/ml, while all female patients included in this study yielded at least 5 oocytes for treatment. Sperm count, motility, and semen volume were recorded according to standard WHO reference guidelines and correlated with PLCzeta profiles obtained via immunoblotting and immunofluorescence. Appropriate fertility treatments all were performed in the clinic at the KFSHRC following routine standard operating protocols, and fertilisation success determined by successful observation of second polar body extrusion. RESULTS AND DISCUSSION: Four distinct PLCzeta patterns were observed at the equatorial, acrosomal+equatorial regions of the sperm head, alongside a dispersed pattern, and a population of sperm without any PLCzeta. Acrosomal+equatorial PLCzeta correlated most to sperm health, while dispersed PLCzeta correlated to decreased sperm viability. Total levels of PLCzeta exhibited significant correlations with sperm parameters. PLCzeta variance corresponded to reduced sperm health, potentially underlying cases of male subfertility and increasing male age. Finally, significantly higher levels of PLCzeta were exhibited by cases of fertilisation success, alongside higher proportions of Ac+Eq, and lower levels of dispersed PLCzeta. CONCLUSIONS: PLCzeta potentially represents a biomarker of sperm health, and fertilisation capacity in general cases of patients seeking fertility treatment, and not just cases of repeated fertilization. Further focused investigations are required with larger cohorts to examine the full clinical potential of PLCzeta.