Assisted oocyte activation overcomes fertilization failure in globozoospermic patients regardless of the DPY19L2 status

Kuentz, Paul; Meerschaut, Frauke Vanden; ElInati, Elias; Nasr-Esfahani, Mohammad Hossein; Gürgan, Timur; Iqbal, Naeem; Carré-Pigeon, F.; Brugnon, Florence; Gitlin, Susan; Calle, Juan Velez de la; Kilani, Zaid; Sutter, Petra De; Viville, Stéphane

doi:10.1093/humrep/det005

Cited by 57 publications

(44 citation statements)

References 6 publications

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“…Another reason for different clinical manifestations between these couples could be because of other genetic defects which have been reported along with DPY19L2 deletion (Chianese et al, 2015). While we did not assess DPY19L2 deletion in these 12 cases, as it was not our aim, but based on our previous study (Kuentz et al, 2013) we expect 70% of cases having DPY19L2 deletion. Recently, we compared physical and mental health of children between couples undergoing ICSI-AOA using ionomycin and conventional ICSI.…”

Section: Discussionmentioning

confidence: 94%

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: Discussionmentioning

confidence: 94%

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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“…Fertilization failures in the patients with globozoospermia have been attributed to a deficiency in oocyte activation capacity [ 16 ] . A recent study of a large cohort of globozoospermic patients has shown that the fertilization rates after ICSI with assisted oocyte activation (AOA) are restored to normal when compared with conventional ICSI in globozoospermic patients with and without a mutations in the DPY19L2 gene [ 17 ] . Thus, it was proposed that the first-line therapeutic approach for complete globozoospermia should include ICSI with AOA regardless of the DPY19L2 status.…”

Section: Discussionmentioning

confidence: 99%

A Homozygous Deletion of the DPY19L2 Gene is a Cause of Globozoospermia in Men From the Republic of Macedonia

Noveski

Madjunkova

Maleva

et al. 2013

Balkan Journal of Medical Genetics

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Globozoospermia is a rare but severe teratozoospermia, characterized by ejaculates consisting completely of round-headed spermatozoa that lack an acrosome or, in partial globozoospermia, containing a variable proportion (20.0–90.0%) of acrosomeless spermatozoa. Men that are affected with total globozoospermia are infertile, and even the application of intracytoplasmic sperm injection (ICSI) has met with disappointingly low success rates. In humans, several case reports of globozoospermia have demonstrated that two or more siblings were affected in each family, which suggested a genetic component to this disease. Currently, three genes are known to be associated with total globozoospermia in humans, SPATA16 , PICK1 and DPY19L2 genes. Mutations in SPATA16 and PICK1 are rare causes of globozoospermia, found in only one patient each. Several studies have suggested that DPY19L2 mutations are the major cause of globozoospermia in patients from different ethnic origins and different geographic regions. The most common DPY19L2 mutation is the 200 kb deletion arising from a nonallelic homologous recombination (NAHR) between the flanking low copy repeats (LCRs). Here we describe the presence of a homozygous deletion of the DPY19L2 gene in two infertile Macedonian patients with 100.0% round headed spermatozoa, thus suggesting that this deletion represents a major cause of globozoospermia among Macedonian men.

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“…Moreover, Kuentz and colleagues showed that in a series of 66 cycles, in case of mutations of DPY19L2, and in the absence of AOA, the fertilization rate remains very low. The fertilization rate was restored completely through AOA [39]. Although the function of DPY19L2 is unknown, the absence of the protein produces a destabilization of the link between the acrosome and the nuclear envelope, indicating that the subcellular location of PLCζ in human sperm is consistent with its role as the sperm-borne activating factor.…”

Section: Plcζ Protein Localization and Fertilization Abilitymentioning

confidence: 91%

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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Assisted oocyte activation overcomes fertilization failure in globozoospermic patients regardless of the DPY19L2 status

Cited by 57 publications

References 6 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

A Homozygous Deletion of the DPY19L2 Gene is a Cause of Globozoospermia in Men From the Republic of Macedonia

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

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