Abstract
Background Oocyte activation is driven by intracellular calcium (Ca2+) oscillations induced by sperm-specific PLC zeta, abrogation of which causes oocyte activation deficiency in humans. Clinical PLC zeta investigations have been limited to severe male infertility conditions, while PLC zeta levels and localisation patterns have yet to be associated with general sperm viability.
Materials and Methods PLC zeta profiles were examined within a general population of males attending a fertility clinic (65 patients; aged 29-53), examining PLC zeta throughout various fractions of sperm viability. Male recruitment criteria required a minimum sperm count of 5 x 10(6) 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 PLC zeta 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 PLC zeta patterns were observed at the equatorial, acrosomal + equatorial regions of the sperm head, alongside a dispersed pattern, and a population of spermatozoa without any PLC zeta. Acrosomal + equatorial PLC zeta correlated most to sperm health, while dispersed PLC zeta correlated to decreased sperm viability. Total levels of PLC zeta exhibited significant correlations with sperm parameters. PLC zeta variance corresponded to reduced sperm health, potentially underlying cases of male sub-fertility and increasing male age. Finally, significantly higher levels of PLC zeta were exhibited by cases of fertilisation success, alongside higher proportions of Ac + Eq, and lower levels of dispersed PLC zeta.
Conclusions PLC zeta 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 PLC zeta.