Phospholipase C? rescues failed oocyte activation in a prototype of male factor infertility  

Oleh:

Nomikos, Michail ; Yu, Yuansong ; Elgmati, Khalil ; Theodoridou, Maria

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Fertility and Sterility (keterangan: ada di ClinicalKey) vol. 99 no. 01 (Jan. 2013), page 76-85.
Topik: ANDROLOGY; Fertilization; male infertility; oocyte activation; phospholipase C; PLC-zeta

Ketersediaan

Perpustakaan FK Nomor Panggil: F02.K.2013.03 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Objective To determine the effect of infertility-linked sperm phospholipase C? (PLC?) mutations on their ability to trigger oocyte Ca2+ oscillations and development, and also to evaluate the potential therapeutic utility of wild-type, recombinant PLC? protein for rescuing failed oocyte activation and embryo development. Design Test of a novel therapeutic approach to male factor infertility. Setting University medical school research laboratory. Patient(s) Donated unfertilized human oocytes from follicle reduction. Intervention(s) Microinjection of oocytes with recombinant human PLC? protein or PLC? cRNA and a Ca2+-sensitive fluorescent dye. Main Outcome Measure(s) Measurement of the efficacy of mutant and wild-type PLC?-mediated enzyme activity, oocyte Ca2+ oscillations, activation, and early embryo development. Result(s) In contrast to the wild-type protein, mutant forms of human sperm PLC? display aberrant enzyme activity and a total failure to activate unfertilized oocytes. Subsequent microinjection of recombinant human PLC? protein reliably triggers the characteristic pattern of cytoplasmic Ca2+ oscillations at fertilization, which are required for normal oocyte activation and successful embryo development to the blastocyst stage. Conclusion(s) Dysfunctional sperm PLC? cannot trigger oocyte activation and results in male factor infertility, so a potential therapeutic approach is oocyte microinjection of active, wild-type PLC? protein. We have demonstrated that recombinant human PLC? can phenotypically rescue failed activation in oocytes that express dysfunctional PLC?, and that this intervention culminates in efficient blastocyst formation.

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