Transgenic RNA Interference Reveals Role for Mouse Sperm Phospholipase Cζ in Triggering Ca2+ Oscillations During Fertilization1

Knott, Jack H.; Kurokawa, Manabu; Fissore, Rafael A.; Schultz, Richard M.; Williams, Carmen J.

doi:10.1095/biolreprod.104.036244

Cited by 166 publications

(102 citation statements)

References 20 publications

(16 reference statements)

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“…For instance, immunodepletion of PLC in sperm extracts prevents those extracts from inducing Ca 2ϩ release in eggs (Saunders et al, 2002). Furthermore, eggs fertilized with sperm from transgenic mice expressing short hairpin RNAs targeting PLC exhibit a shortened duration of Ca 2ϩ release, resulting in a lower rate of egg activation (Knott et al, 2005). However, the phenotype of a knock-out mouse lacking PLC has not yet been reported.…”

Section: Triggers Of Egg Activation Spermmentioning

confidence: 99%

Transitioning from egg to embryo: Triggers and mechanisms of egg activation

Horner

Wolfner

2008

Developmental Dynamics

181

177

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The transition from mature oocyte to developing embryo requires a coordinated series of events, collectively known as egg activation. Egg activation includes changes to egg coverings to prevent polyspermy, release of oocyte meiotic arrest, generation of haploid female and male pronuclei, changes in maternal mRNAs and protein populations, and cytoskeletal rearrangements. In many animals, egg activation is triggered by fertilization, which increases intracellular calcium within the oocyte and thereby regulates molecular events of egg activation. In other animals, fertilization-independent external signals, including mechanical stimulation of eggs and/or changes in ionic milieu, trigger activation. Recent studies have clarified the upstream portion of pathways leading to eggshell changes and cell cycle resumption and have identified activation-induced changes in maternal mRNA and protein profiles that can identify molecular players in the downstream events of egg activation. We review signals that trigger activation and how they link to subsequent molecular events of egg activation. Developmental Dynamics 237:527-544, 2008.

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Section: Triggers Of Egg Activation Spermmentioning

confidence: 99%

Transitioning from egg to embryo: Triggers and mechanisms of egg activation

Horner

Wolfner

2008

Developmental Dynamics

181

177

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“…spermatogenesis hinders Ca 2+ oscillations and subsequent oocyte activation [18,19]. Furthermore, human sperm devoid of PLCζ fail to induce Ca 2+ oscillations [20], and two point mutations, H233L and H398P, have been characterized to affect PLCζ functionality.…”

Section: Introductionmentioning

confidence: 99%

PLCζ sequence, protein levels, and distribution in human sperm do not correlate with semen characteristics and fertilization rates after ICSI

Ferrer-Vaquer¹,

Barragán²,

Fréour

et al. 2016

J Assist Reprod Genet

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Purpose Sperm-borne PLCζ protein induces Ca 2+ oscillations in the oocyte and is believed to play a major role during oocyte activation. However, its implication in fertilization failure following ICSI is still debated. We analyzed PLCζ gene sequence, protein expression level, and localization in both patients with previous failed fertilization by ICSI and sperm donors with proven fertility in order to assess the association of PLCζ with both sperm characteristics and ability to fertilize. Methods Semen from 15 patients and 13 sperm donors with proven fertility was included in the study. Analysis of the PLCζ gene sequence, protein expression through Western blot, and protein localization by immunofluorescence were performed. Results Two patients with total fertilization failure presented mutations in heterozygosis in the PLCζ gene. Comparison with donor sample sequences displayed comparable SNP allele frequency. Distribution pattern of PLCζ did not vary significantly between donor and patient samples. Levels of PLCζ protein in sperm cells showed an interindividual variability both in patient and donor samples. Several SNPs previously reported in infertile patients were also present in fertile men. ConclusionFailed fertilization occurs even when levels and distribution of PLCζ protein are within normal range. PLCζ seems to be a necessary but not sufficient factor in determining the molecular pathway involved in oocyte activation.

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“…reticulum (ER) leading to oocyte activation and zygote formation [2][3][4][5][6]. Furthermore, absence of PLC-ζ from sperm extracts, or inhibition of PLC-ζ expression in sperm by RNA interference, impairs cytosolic Ca 2+ release and reduces the amplitude and duration of Ca 2+ oscillations [2,3,7].…”

Section: Introductionmentioning

confidence: 99%

Phospholipase C-zeta deficiency as a cause for repetitive oocyte fertilization failure during ovarian stimulation for in vitro fertilization with ICSI: a case report

Chithiwala

Lee

Hill

et al. 2015

J Assist Reprod Genet

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Purpose The purpose of this study is to describe impaired oocyte fertilization from phospholipase C-zeta (PLC-ζ) deficiency in normal-appearing sperm that was successfully treated using calcium (Ca 2+ ) ionophore with intracytoplasmic sperm injection (ICSI) of oocytes matured in vitro. Methods An infertile couple undergoing in vitro fertilization (IVF) experienced failed oocyte fertilization following ICSI with normal-appearing sperm. A semen sample collected from the patient was used to assess the expression of sperm PLC-ζ protein by Western blot analysis and immunofluorescence and PLC-ζ bioactivity by an in vitro model of Ca 2+ release. A second IVF cycle was performed using Ca 2+ ionophore with ICSI to enhance Ca 2+ -induced oocyte activation of oocytes matured in vitro.Results Sperm PLC-ζ protein deficiency was demonstrated by Western blot analysis and immunofluorescence and confirmed by reduced PLC-ζ bioactivity using an in vitro model of Ca 2+ release. Nevertheless, with this sperm and supplementation of Ca 2+ ionophore following ICSI, fertilization of four of six oocytes matured in vitro was obtained. In addition, four embryos underwent cleavage and two of them reached the blastocyst stage. Transfer of these blastocysts into the uterus led to a single pregnancy and live birth. Conclusions Deficiency of PLC-ζ in normal-appearing human sperm is associated with impaired Ca 2+ -dependent oocyte activation during ICSI. Under this condition, use of Ca 2+ ionophore following ICSI of oocytes matured in vitro improves embryo developmental competence, possibly through the activation of Ca 2+ -dependent mechanisms governing fertilization and preimplantation embryogenesis.

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Transgenic RNA Interference Reveals Role for Mouse Sperm Phospholipase Cζ in Triggering Ca2+ Oscillations During Fertilization1

Cited by 166 publications

References 20 publications

Transitioning from egg to embryo: Triggers and mechanisms of egg activation

Transitioning from egg to embryo: Triggers and mechanisms of egg activation

PLCζ sequence, protein levels, and distribution in human sperm do not correlate with semen characteristics and fertilization rates after ICSI

Phospholipase C-zeta deficiency as a cause for repetitive oocyte fertilization failure during ovarian stimulation for in vitro fertilization with ICSI: a case report

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