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

Sperm-specific phospholipase C zeta (PLCζ) 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 PLCζ with forms of male infertility in humans where oocyte activation fails. However, very few studies have examined potential relationships between PLCζ 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 PLCζ 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 PLCζ protein levels and localization patterns in sperm, and PLCζ 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 PLCζ protein and mRNA in sperm and testes, respectively, when both strains were examined. Furthermore, advancing male age altered the predominant pattern of PLCζ localization in mouse sperm, with younger mice exhibiting predominantly post-acrosomal, and older mice exhibiting both post-acrosomal and acrosomal populations of PLCζ. 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 PLCζ levels and localization patterns, indicating that aging male mice from different strains may serve as useful models to investigate PLCζ in cases of male infertility and subfertility in humans.

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

BACKGROUND: Oocyte activation is driven by intracellular calcium (Ca2+ ) 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. MATERIALS AND METHODS: 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 × 106 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. RESULTS AND DISCUSSION: 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. CONCLUSIONS: 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.

Comparative analysis of quantity and quality of biomedical publications in Gulf Cooperation Council countries from 2011-2013.

OBJECTIVES:   To compare the research productivity of different Gulf Cooperation Council (GCC) countries in the field of biomedical sciences from 2011-2013.  METHODS: This is a retrospective study conducted in the College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. Data on the biomedical publications originating from GCC countries published between January 2011 to December 2013 was searched via MEDLINE using PubMed. The total number of publications emanating from each country was normalized with the country's population. The mean impact factor (IF) of all the publications in a year was calculated for comparative analysis.  RESULTS: A total of 11,000 publications were retrieved via MEDLINE using PubMed, out of which, 9222 were selected for analysis. A successive increase in the number of publications by every country was observed. The most striking increase in the number of publications was from Saudi Arabia. However, after normalization with population, the performance of Oman, Qatar, and Kuwait looks far better than Saudi Arabia in terms of research productivity. Data on mean IF showed that the overall mean IF of all GCC countries has remained largely unchanged except Oman. Although Oman had a comparatively low mean IF value in 2011, they recorded a tremendous improvement in successive years.  CONCLUSION: All GCC countries underwent an increase in quantitative research productivity over the last 3 years. However, no increase in quality of research publications was noted based on the proxy reports of mean journal IF.

Research-oriented series: a portal into the culture of biomedical research for junior medical students at Alfaisal University in Saudi Arabia.

Student contributions to research have been shown to effectively reflect on their communication and critical thinking skills. Short-term research courses offer opportunities for medical students to advance their research experience in subsequent high-demanding long-term research opportunities. The purpose of the present study was to describe the development, implementation, and evaluation of a research-oriented series (ROS) on undergraduate students at Alfaisal University in Saudi Arabia. The ROS was designed to comprise eight sessions. Each session addressed core principles and the practice of research concepts and was based on theoretical morning sessions supplemented by afternoon practical sessions delivered by experienced senior medical students and faculty members. Students were assessed comprehensively by the end of the ROS. The series was conducted twice, and 35 students were involved each time. A total of 70 enrolled students (35 men and 35 women) with grade point averages of >3.5 and <3.5 were asked to fill out an anonymous, online, self-administered questionnaire assessing their perception of knowledge, skills, and confidence after attending the ROS and evaluating their senior peers. Ninety percent of the medical students responded to the online survey and rated the ROS highly in improving their research knowledge, skills, and confidence. Male students reported significant gains compared with their female peers (P<0.05). Grade point averages did not play a role in student gains after attending the ROS. Qualitative responses were in support of three recurring themes favoring the unique learning environment in the ROS. In conclusion, the ROS offers a short-term systematic approach to fundamental steps and concepts of biomedical research.