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

Oocyte activation is driven by intracellular calcium (Ca ) 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. 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 × 10 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. 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. 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.Healthcare Research Fellowship Award (HF-14-16) made by Health and Care Research Wales (HCRW). JK was supported by a Healthcare Research Fellowship Award (HF‐14‐16) made by Health and Care Research Wales (HCRW). This study was also supported by a National Science, Technology and Innovation plan (NSTIP) project grant (15‐MED4186‐20) awarded by the King Abdulaziz City for Science and Technology (KACST) to JK, AMA and FAL

Advancing male age differentially alters levels and localization patterns of PLCzeta in sperm and testes from different mouse strains

Sperm-specific phospholipase C zeta (PLC) initiates intracellular calcium (Ca2+) transients which drive a series of concurrent events collectively termed oocyte activation. Numerous investigations have linked abrogation and absence/reduction of PLC with forms of male infertility in humans where oocyte activation fails. However, very few studies have examined potential relationships between PLC and advancing male age, both of which are increasingly considered to be major effectors of male fertility. Initial efforts in humans may be hindered by inherent PLC variability within the human population, alongside a lack of sufficient controllable repeats. Herein, utilizing immunoblotting, immunofluorescence, and quantitative reverse transcription PCR (qRT-PCR) we examined for the first time PLC protein levels and localization patterns in sperm, and PLC mRNA levels within testes, from mice at 8 weeks, 12 weeks, 24 weeks, and 36 weeks of age, from two separate strains of mice, C57BL/6 (B6; inbred) and CD1 (outbred). Collectively, advancing male age generally diminished levels and variability of PLC protein and mRNA in sperm and testes, respectively, when both strains were examined. Furthermore, advancing male age altered the predominant pattern of PLC localization in mouse sperm, with younger mice exhibiting predominantly post-Acrosomal, and older mice exhibiting both post-Acrosomal and acrosomal populations of PLC. However, the specific pattern of such decline in levels of protein and mRNA was strain-specific. Collectively, our results demonstrate a negative relationship between advancing male age and PLC levels and localization patterns, indicating that aging male mice from different strains may serve as useful models to investigate PLC in cases of male infertility and subfertility in humans

Launching COVID-19 vaccination in Saudi Arabia: Lessons learned, and the way forward

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV- 2) emerged in Wuhan City, China. The SARS-CoV-2 crossed borders and quickly transformed into a "Public health emergency of international concern". Countries around the globe are in the race to achieve herd immunity. We describe the steps taken by Saudi Arabia to achieve this goal