Expression of a truncated form of KIT tyrosine kinase in human spermatozoa correlates with sperm DNA integrity

Muciaccia, Barbara; Sette, Claudio; Paronetto, Maria Paola; Barchi, Marco; Pensini, Simona; D’Agostino, Angela; Gandini, L.; Geremia, Raffaele; Stefanini, Mario; Rossi, Pellegrino

doi:10.1093/humrep/deq168

Cited by 40 publications

(36 citation statements)

References 66 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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“…Later on, a truncated Kit product, TR-KIT (an intracellular protein corresponding to the carboxy-terminal portion of the kinase domain), is specifically expressed in post-meiotic stages of spermatogenesis, and is accumulated in mature spermatozoa both in mice and humans (Sorrentino et al, 1991;Rossi et al, 1992;Albanesi et al, 1996;. Sette et al, 1997;Muciaccia et al, 2010). In human spermatozoa TR-KIT is located in the equatorial region, the area involved in sperm-egg fusion (Muciaccia et al, 2010).…”

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confidence: 99%

“…Sette et al, 1997;Muciaccia et al, 2010). In human spermatozoa TR-KIT is located in the equatorial region, the area involved in sperm-egg fusion (Muciaccia et al, 2010). Indeed, TR-KIT is a candidate as one of the sperm-borne factors required for egg activation at fertilization (Sette et al, 1997(Sette et al, , 1998(Sette et al, , 2002.…”

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confidence: 99%

“…While it is known that TR-KIT expression in spermatids depends on the activation of a cell and developmental stage-specific promoter within intronic regions of both the mouse and the human Kit gene (Albanesi et al, 1996;Paronetto et al, 2004;Muciaccia et al, 2010), much less information has been available for long time about the transcriptional mechanisms which control expression of the full-length receptor in mitotic germ cells and in oocytes.…”

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confidence: 99%

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Transcriptional control of KIT gene expression during germ cell development

Rossi¹

2013

Int. J. Dev. Biol.

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The characterization of the mechanisms that regulate KIT expression in germ cells at different times of their development is important not only in the field of reproduction, but also for a better understanding of the biology of testicular germ cell tumors (TGCTs). Indeed this tyrosine kinase receptor, besides being essential for the survival and proliferation of primordial germ cells (PGCs) and for postnatal spermatogenesis and oogenesis, is also frequently overexpressed or constitutively active due to activating mutations in carcinoma in situ of the testis and in seminomas. In this review, I will summarize available data about the transcriptional mechanisms involved in the control of Kit expression in the germline. Variable mechanisms, involving different germ cell-specific transcription factors, are operating in the various developmental stages: SOX2 and SOHLH1/2 act as direct positive regulators in PGCs and in postnatal spermatogonia, respectively, whereas PLZF suppresses KIT expression in spermatogonial stem cells. DMRT1, acting through indirect mechanisms, suppresses KIT transcription in fetal gonocytes, while activating it in differentiating spermatogonia.

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“…The truncated c-kit protein is present in primary tumors and shows a correlation between Tr-kit expression and activation of the Src pathway in the advanced stages of human prostate cancer (Paronetto et al 2004). Recently it was shown that Tr-kit is present in the equatorial region of human spermatozoa, which are the first sperm components that enter into the oocyte cytoplasm after fusion with the egg (Muciaccia et al 2010). …”

Section: Tr-kitmentioning

confidence: 99%

Phospho-Signaling at Oocyte Maturation and Fertilization: Set Up for Embryogenesis and Beyond Part II. Kinase Regulators and Substrates

Hasan¹,

Mutoh²,

Kihira³

et al. 2012

Embryogenesis

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Expression of a truncated form of KIT tyrosine kinase in human spermatozoa correlates with sperm DNA integrity

Cited by 40 publications

References 66 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

Transcriptional control of KIT gene expression during germ cell development

Phospho-Signaling at Oocyte Maturation and Fertilization: Set Up for Embryogenesis and Beyond Part II. Kinase Regulators and Substrates

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