Sperm‐derived WW domain‐binding protein, PAWP, elicits calcium oscillations and oocyte activation in humans and mice

Aarabi, Mahmoud; Bałakier, Hanna; Bashar, Siamak; Moskovtsev, Sergey I.; Šutovský, Peter; Librach, Clifford L.; Oko, Richard

doi:10.1096/fj.14-256495

Cited by 107 publications

(121 citation statements)

References 40 publications

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“…Among these factors, PLCf has emerged as the strongest candidate and several studies have shown the correlation between absence or deficiency of PLCf with failed fertilization in globozoospermic men (Heytens et al, 2009;and Aghajanpour et al, 2011). However, a growing body of evidence has challenged the importance of PLCf as the key SOAF and proposed other candidate proteins, particularly PAWP and TR-KIT, as the major SOAFs (Muciaccia et al, 2010;Aarabi et al, 2014b;Amdani et al, 2015;Nomikos et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Expression profile ofPLCζ,PAWP,andTR-KITin association with fertilization potential, embryo development, and pregnancy outcomes in globozoospermic candidates for intra-cytoplasmic sperm injection and artificial oocyte activation

Tavalaee

Nasr-Esfahani

2016

Andrology

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SUMMARYSperm-mediated oocyte activation critically depends upon appropriate expression and assembly of sperm-borne oocyte-activating factors (SOAFs) during spermiogenesis. Several factors have been considered as candidate for SOAFs over the recent years. However, little is known about the expression profile of these candidates and their potential contribution to the clinical outcomes of intra-cytoplasmic sperm injection (ICSI), particularly in globozoospermia. This study investigated the expression profile of PLCf, PAWP, and TR-KIT and clinical outcomes of ICSI in 12 men with total globozoospermia and compared with 12 fertile individuals. Levels of PLCf, PAWP, and TR-KIT mRNA in the spermatozoa of fertile men were significantly higher than the corresponding values of the globozoospermic subjects. Interestingly, at protein level, expressions of these factors in the cases assessed were low in globozoospermic individuals. Fertilization rates following artificial oocyte activation (AOA) in the majority of globozoospermic couples were higher than the expected 30% cut-off value reported for individuals with failed or low fertilization rate. Clinical outcomes of ICSI-AOA were dependent on inter-individual variation in globozoospermic couples. None of the SOAFs assessed could provide a greater prediction value with respect to fertilization rate in globozoospermic couples which underwent ICSI-AOA. High fertilization (56.06%) and pregnancy (41.7%) rates accomplished in this study following ICSI-AOA indicated that expression profiles of PLCf, PAWP, and TR-KIT were low in globozoospermic individuals, and ICSI combined with artificial oocyte activation could mimic physiological calcium changes which occur during fertilization.

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Section: Introductionmentioning

confidence: 99%

Expression profile ofPLCζ,PAWP,andTR-KITin association with fertilization potential, embryo development, and pregnancy outcomes in globozoospermic candidates for intra-cytoplasmic sperm injection and artificial oocyte activation

Tavalaee

Nasr-Esfahani

2016

Andrology

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“…We need further systematic studies to identify the best method to activate human ROSI oocytes. Other oocyte-activating agents to be considered include: Ca 2+ ionophore (20,45,46), phosphatidyl inositol (47,48), phospholipase Cζ (49-51), 4-(diemethylamino) pyridine (52), and postacrosomal protein PAWP (53)(54)(55).…”

Section: Possible Reasons For Previous Failures Of Human Rosimentioning

confidence: 99%

Fourteen babies born after round spermatid injection into human oocytes

Tanaka

Nagayoshi

Takemoto

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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During the human in vitro fertilization procedure in the assisted reproductive technology, intracytoplasmic sperm injection is routinely used to inject a spermatozoon or a less mature elongating spermatid into the oocyte. In some infertile men, round spermatids (haploid male germ cells that have completed meiosis) are the most mature cells visible during testicular biopsy. The microsurgical injection of a round spermatid into an oocyte as a substitute is commonly referred to as round spermatid injection (ROSI). Currently, human ROSI is considered a very inefficient procedure and of no clinical value. Herein, we report the birth and development of 14 children born to 12 women following ROSI of 734 oocytes previously activated by an electric current. The round spermatids came from men who had been diagnosed as not having spermatozoa or elongated spermatids by andrologists at other hospitals after a first Micro-TESE. A key to our success was our ability to identify round spermatids accurately before oocyte injection. As of today, all children born after ROSI in our clinic are without any unusual physical, mental, or epigenetic problems. Thus, for men whose germ cells are unable to develop beyond the round spermatid stage, ROSI can, as a last resort, enable them to have their own genetic offspring.

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“…We cannot exclude the presence and relevance for the phenotype observed of alteration in other candidate activation molecules, such as PAWP [27,28], however, due to the limited amount of patient sample available for study, we elected to focus on PLCζ.…”

Section: Icsi Failure and Plcζ Presence/distributionmentioning

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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Sperm‐derived WW domain‐binding protein, PAWP, elicits calcium oscillations and oocyte activation in humans and mice

Cited by 107 publications

References 40 publications

Expression profile ofPLCζ,PAWP,andTR-KITin association with fertilization potential, embryo development, and pregnancy outcomes in globozoospermic candidates for intra-cytoplasmic sperm injection and artificial oocyte activation

Expression profile ofPLCζ,PAWP,andTR-KITin association with fertilization potential, embryo development, and pregnancy outcomes in globozoospermic candidates for intra-cytoplasmic sperm injection and artificial oocyte activation

Fourteen babies born after round spermatid injection into human oocytes

PLCζ disruption with complete fertilization failure in normozoospermia

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