Phospholipase C zeta (PLCζ): Oocyte activation and clinical links to male factor infertility

Amdani, Siti Nornadhirah; Jones, Céline; Coward, Kevin

doi:10.1016/j.jbior.2013.07.005

Cited by 64 publications

(52 citation statements)

References 84 publications

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“…That is why a correlation between certain types of male infertility and the aberrant expression, localization, structure, and function of PI-PLC in human sperm has been determined. The potential therapeutic role of PI-PLC could therefore be linked to the identifi cation of male patients that are defi cient in PI-PLC , and for them an alternative therapeutic approach, based on assisted reproductive technology, could be useful for rescuing the impaired oocyte activation ( 92 ).…”

Section: Splicing Variants Of Pi-plcmentioning

confidence: 99%

Phosphoinositide-specific phospholipase C in health and disease

Cocco

Follo

Manzoli

et al. 2015

Journal of Lipid Research

134

100

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Section: Splicing Variants Of Pi-plcmentioning

confidence: 99%

Phosphoinositide-specific phospholipase C in health and disease

Cocco

Follo

Manzoli

et al. 2015

Journal of Lipid Research

134

100

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“…The patient ultimately conceived by AOA, and a healthy baby girl was born. 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].…”

Section: Discussionmentioning

confidence: 99%

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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“…Protein relocation/ translocation is not an unusual event in sperm biology as demonstrated for IZUMO that translocates from the acrosomal membrane to the equatorial segment plasma membrane and MN13 that diffuses from the acrosome to the PAS . MN13 is one of the numerous candidates to be the sperm factor that triggers oocyte activation (for a review, see ex Amdani et al (2013)). Currently, however, the most quoted is PLCz, the sperm-specific phospholipase C that generates repetitive Ca 2C transients into the ooplasm of the fertilized oocyte, thus leading to oocyte activation (Saunders et al 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Currently, however, the most quoted is PLCz, the sperm-specific phospholipase C that generates repetitive Ca 2C transients into the ooplasm of the fertilized oocyte, thus leading to oocyte activation (Saunders et al 2002). A key, as yet unanswered, question is, however, how the enzyme, inactive within sperm, is activated into the oocyte (Amdani et al 2013).…”

Section: Discussionmentioning

confidence: 99%

USP8/UBPy-regulated sorting and the development of sperm acrosome: the recruitment of MET

Berruti

Paiardi

2015

Reproduction

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The acrosome is a peculiar vacuole that at fertilization undergoes the acrosome reaction (AR), an event unique in the sperm life. Contents released promote sperm penetration through oocyte's investments; membranous components are involved in sperm-egg interaction/fusion. Therefore, both constituents play a role in fertilization. The biogenesis of this vacuole, however, has not been clarified yet; recently, it has been proposed as a novel lysosome-related organelle (LRO). Our research focuses on the involvement of the endosomal pathway in acrosomogenesis starting from the early phases. The trafficking sorted by USP8/UBPy, an endosomal regulator recently described as a compelling candidate for male fertility gene, was investigated in comparison to that of SP56, a marker of the biosynthetic pathway. Mouse spermatids were double/triple immunolabeled and examined by confocal microscopy. The contribution of the vesicular traffic assisted by the cortical microtubule array was also evaluated in nocodazole-treated spermatids. USP8/UBPy-sorted cargo contributes early to acrosomogenesis and its trafficking is microtubule mediated. It was identified, through co-immunoprecipitation/co-immunolocalization assays, that the membrane receptor MET, described herein for the first time in spermatids, as an USP8/UBPy-target substrate is delivered to the acrosome. MET and USP8/UBPy still colocalize in epididymal spermatozoa. Following the AR, MET and USP8/UBPy show a distinct fate. MET, in particular, translocates at the PAS, the post acrosomal segment known to harbor sperm-borne factors involved in oocyte activation. Overall, our results support the concept of the acrosome as a LRO and provide evidence for the identification of MET as a tyrosine kinase receptor that may play a role in fertilization.

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Phospholipase C zeta (PLCζ): Oocyte activation and clinical links to male factor infertility

Cited by 64 publications

References 84 publications

Phosphoinositide-specific phospholipase C in health and disease

Phosphoinositide-specific phospholipase C in health and disease

PLCζ disruption with complete fertilization failure in normozoospermia

USP8/UBPy-regulated sorting and the development of sperm acrosome: the recruitment of MET

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