Variance in total levels of phospholipase C zeta (PLC-ζ) in human sperm may limit the applicability of quantitative immunofluorescent analysis as a diagnostic indicator of oocyte activation capability

Kashir, Junaid; Jones, Céline; Mounce, Ginny; Ramadan, Walaa M.; Lemmon, Bernadette; Heindryckx, Björn; Sutter, Petra De; Parrington, John; Turner, Kevin B.; Child, Tim; McVeigh, Enda; Coward, Kevin

doi:10.1016/j.fertnstert.2012.09.001

Cited by 70 publications

(121 citation statements)

References 54 publications

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“…This finding is consistent with a recent report where PLCζ was significantly reduced in patients with previous fertilization failures, even taking into account the variability in PLCζ levels among controls [24]. The source of lower expression of PLCζ remains to be established; altered transcription, translation, or turnover are all possible mechanisms, which so far have not been addressed.…”

Section: Icsi Failure and Plcζ Presence/distributionsupporting

confidence: 90%

“…The source of lower expression of PLCζ remains to be established; altered transcription, translation, or turnover are all possible mechanisms, which so far have not been addressed. Together with its abundance, PLCζ localization can also be related to fertilization failures [17,24]. In consistence with these reports, we found altered localization of PLCζ in the patient sperm.…”

Section: Icsi Failure and Plcζ Presence/distributionsupporting

confidence: 89%

“…One of the most agreed upon factors related to fertilization failure of male origin is PLCζ [22,23]. PLCζ alterations can be due to gene mutations, altered protein expression or cellular localization, absence (globozoospermia), and functionality [16,15,17,24]. The molecular analysis of PLCζ revealed significantly lowered amount and altered distribution of the protein, with no mutations detected.…”

Section: Discussionmentioning

confidence: 99%

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PLCζ disruption with complete fertilization failure in normozoospermia

Durbán¹,

Barragán²,

Colodrón³

et al. 2015

J Assist Reprod Genet

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Purpose Intracytoplasmic sperm injection (ICSI) is widely used to achieve fertilization in the presence of severe male factor, resulting in high fertilization rates. Nevertheless, 1-3 % of couples experience complete fertilization failure after ICSI. When a male factor is identified, assisted oocyte activation (AOA) can help overcome fertilization failures. The objective of this study is to describe a case of repeated complete fertilization failures after ICSI with donor oocytes, and to investigate the molecular and functional aspects of phospholipase C zeta (PLCζ) protein in the patient semen. Methods The patient was a normozoospermic male who had previously fathered, through natural conception, four children by a different partner. Molecular and functional analysis of sperm-specific PLCζ in the patient and control samples by means of gene sequencing, immunocytochemistry, Western blot, mouse oocyte activation test (MOAT), and mouse oocyte calcium analysis (MOCA) were used.Results PLCζ expression levels and distribution were significantly disrupted, although MOAT and MOCA did not indicate a decrease in activation ability. Conclusions Normozoospermic males can have disrupted expression and distribution of PLCζ, and reduced activation ability after ICSI in human oocytes, despite their normal activation potential in functional testing using mouse oocytes. Discrepancy among molecular and functional data might exist, as mutations in the gene sequence may not be the only cause of alteration in PLCζ protein related to activation failures.

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Section: Icsi Failure and Plcζ Presence/distributionsupporting

confidence: 90%

Section: Icsi Failure and Plcζ Presence/distributionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

PLCζ disruption with complete fertilization failure in normozoospermia

Durbán¹,

Barragán²,

Colodrón³

et al. 2015

J Assist Reprod Genet

Self Cite

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“…Specifically, the sperm from these men showed PLC-ζ protein levels that were 40-80 % lower than those of normal-appearing control sperm that were capable of oocyte fertilization [8]. Interestingly, PLC-ζ in the sperm of our patient was either absent or located in the post-acrosomal region and showed a punctate pattern rather than a uniform band in the equatorial region, which is the most consistent location in fertile males [5,24,25]. Nevertheless, it is worth noting that several distribution patterns of PLC-ζ have been reported within sperm without a history of failed oocyte fertilization [25].…”

Section: Discussionmentioning

confidence: 51%

“…Under this circumstance, detecting sperm PLC-ζ deficiency implicates the sperm, rather than the oocyte, as the cause of failed oocyte fertilization, thereby avoiding unnecessary oocyte donation. A critical amount of PLC-ζ in sperm may be required for optimal Ca 2+ -dependent oocyte activation, below which low rates of oocyte fertilization after ICSI are observed (i.e., <30 %) [14], although variable sperm PLC-ζ expression between samples and patients may limit quantitative analysis of PLC-ζ as a diagnostic indicator of oocyte activation [25].…”

Section: Discussionmentioning

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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Comparative biology of sperm factors and fertilization‐induced calcium signals across the animal kingdom

Kashir

Deguchi

Jones

et al. 2013

Molecular Reproduction Devel

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SUMMARYFertilization causes mature oocytes or eggs to increase their concentrations of intracellular calcium ions (Ca 2þ ) in all animals that have been examined, and such Ca 2þ elevations, in turn, provide key activating signals that are required for non-parthenogenetic development. Several lines of evidence indicate that the Ca 2þ transients produced during fertilization in mammals and other taxa are triggered by soluble factors that sperm deliver into oocytes after gamete fusion. Thus, for a broad-based analysis of Ca 2þ dynamics during fertilization in animals, this article begins by summarizing data on soluble sperm factors in non-mammalian species, and subsequently reviews various topics related to a sperm-specific phospholipase C, called PLCz, which is believed to be the predominant activator of mammalian oocytes. After characterizing initiation processes that involve sperm factors or alternative triggering mechanisms, the spatiotemporal patterns of Ca 2þ signals in fertilized oocytes or eggs are compared in a taxon-by-taxon manner, and broadly classified as either a single major transient or a series of repetitive oscillations. Both solitary and oscillatory types of fertilization-induced Ca 2þ signals are typically propagated as global waves that depend on Ca 2þ release from the endoplasmic reticulum in response to increased concentrations of inositol 1,4,5-trisphosphate (IP 3 ). Thus, for taxa where relevant data are available, upstream pathways that elevate intraoocytic IP 3 levels during fertilization are described, while other less-common modes of producing Ca 2þ transients are also examined. In addition, the importance of fertilization-induced Ca 2þ signals for activating development is underscored by noting some major downstream effects of these signals in various animals.Mol. Reprod. Dev. 80: 787À815,

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Variance in total levels of phospholipase C zeta (PLC-ζ) in human sperm may limit the applicability of quantitative immunofluorescent analysis as a diagnostic indicator of oocyte activation capability

Cited by 70 publications

References 54 publications

PLCζ disruption with complete fertilization failure in normozoospermia

PLCζ disruption with complete fertilization failure in normozoospermia

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

Comparative biology of sperm factors and fertilization‐induced calcium signals across the animal kingdom

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