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AuthorSaleh, Alaaeldin
AuthorThanassoulas, Angelos
AuthorAliyev, Elnur
AuthorSwann, Karl
AuthorNaija, Azza
AuthorYalcin, Huseyin C.
AuthorLai, F. Anthony
AuthorNomikos, Michail
Available date2024-05-28T11:06:31Z
Publication Date2024-05-27
Publication NameBiomedicines
Identifierhttp://dx.doi.org/10.3390/biomedicines12061183
CitationSaleh, A.; Thanassoulas, A.; Aliyev, E.; Swann, K.; Naija, A.; Yalcin, H.C.; Lai, F.A.; Nomikos, M. Development of Recombinant PLC-Zeta Protein as a Therapeutic Intervention for the Clinical Treatment of Oocyte Activation Failure. Biomedicines 2024, 12, 1183. https://doi.org/10.3390/biomedicines12061183
URIhttp://hdl.handle.net/10576/55584
AbstractThe sperm-specific phospholipase C zeta (PLCζ) protein is widely considered as the predominant physiological stimulus for initiating the Ca2+ release responsible for oocyte activation during mammalian fertilization. The increasing number of genetic and clinical reports that directly link PLCζ defects and/or deficiencies with oocyte activation failure (OAF) necessitates the use of a powerful therapeutic intervention to overcome such cases of male factor infertility. Currently, in vitro fertilization (IVF) clinics treat OAF cases after intracytoplasmic sperm injection (ICSI) with Ca2+ ionophores. Despite their successful use, such chemical agents are unable to trigger the physiological pattern of Ca2+ oscillations. Moreover, the safety of these ionophores is not yet fully established. We have previously demonstrated that recombinant PLCζ protein can be successfully used to rescue failed oocyte activation, resulting in efficient blastocyst formation. Herein, we produced a maltose binding protein (MBP)-tagged recombinant human PLCζ protein capable of inducing Ca2+ oscillations in mouse oocytes similar to those observed at fertilization. Circular dichroism (CD) experiments revealed a stable, well-folded protein with a high helical content. Moreover, the recombinant protein could retain its enzymatic properties for at least up to 90 days after storage at −80 °C. Finally, a chick embryo model was employed and revealed that exposure of fertilized chicken eggs to MBP-PLCζ did not alter the embryonic viability when compared to the control, giving a first indication of its safety. Our data support the potential use of the MBP-PLCζ recombinant protein as an effective therapeutic tool but further studies are required prior to its use in a clinical setting.
SponsorThis study was performed according to the guidelines of the Qatar University ethical committee. All procedures were ethically approved by the Qatar University Institutional Animal Care and Use Committee (QU-IACUC) (IACUC REFERENCE number: QU-IACUC 007/2021-REN1).
Languageen
PublisherMDPI
Subjectmale infertility
phospholipase C
PLC-zeta
sperm
IVF
ICSI
fertilization
OAF
TitleDevelopment of Recombinant PLC-Zeta Protein as a Therapeutic Intervention for the Clinical Treatment of Oocyte Activation Failure
TypeArticle
Issue Number6
Volume Number12
ESSN2227-9059
dc.accessType Open Access


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