Project Summary

Infertility is a rising health issue with approximately 1 in 6 people of the adult population is affected globally, according to a 2023 World Health Organization (WHO) report. Males are estimated to contribute in approximately half of the overall infertility cases. Assisted Reproductive technology (ART) including IVF and ICSI plays a major role in helping infertile patients to have children. Despite advancement in ART, success rate ranges between 30-40%/cycle in terms of live birth, reflecting major gaps in our knowledge of molecular mechanisms governing successful fertilization and early embryonic development.

PLCζ (Phospholipase C-zeta) is known as the sperm factor and required for calcium oscillation, a critical process for oocyte activation and fertilization. Data from human and mice has shown that PLCζ expression level and sperm localization are important for successful fertilization and pregnancy. Moreover, we created PLCζ knockout mouse models using CRISPR/CAS9 technology to model its function in mouse oocyte fertilization and early embryonic development. The PLCζ knockout mouse models revealed a novel roles in early events of embryos cellular division. We believe that PLCζ protein is an excellent biomarker for sperm health and male fertility and potential infertility therapeutic.

Collaborators

Junaid Kashir, Serdar Coskun, Islam Saadeldin, Naif alhathal.

Figures

Representative PLCζ immunofluorescence microscopy in mouse sperm. (A) Observed PLCζ localization patterns (green fluorescence; left column) alongside corresponding brightfield images (right column) in sperm from wildtype and Plcζ knockout (KO) mouse strains. (B) Histogram indicating quantification of PLCζ fluorescence in sperm from wildtype and Plcζ knockout (KO) mouse strains. (Figure from Kashir J, Mistry BV, Rajab MA, et al. The mammalian sperm factor phospholipase C zeta is critical for early embryo division and pregnancy in humans and mice. Hum Reprod. 2024;39(6):1256-1274.
Histograms representing embryogenic efficacy of embryos generated following IVF experiments using oocytes from wildtype (WT) females and sperm of WT (red) or Plcζ knockout (KO) (grey) strains of mice indicating (A) proportions of embryos generated at specific developmental milestones, and (B) time taken (h) to reach specific developmental morphokinetic milestones. Asterisk (*) indicates a statistically significant (P ≤ 0.05) difference. (Figure from Kashir J, Mistry BV, Rajab MA, et al. The mammalian sperm factor phospholipase C zeta is critical for early embryo division and pregnancy in humans and mice. Hum Reprod. 2024;39(6):1256-1274.
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