title: PLCζ disruption with complete fertilization failure in normozoospermia.
abstract: OBJECTIVE
  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.
authors.affiliation: Clínica EUGIN, Travessera de les Corts 322, 08029, Barcelona, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Durban
authors.forename: Montserrat
authors.initials: M
authors.lastname: Barragán
authors.forename: Marta
authors.initials: M
authors.lastname: Colodron
authors.forename: Minerva
authors.initials: M
authors.lastname: Ferrer-Buitrago
authors.forename: Petra
authors.initials: P
authors.lastname: De Sutter
authors.forename: Björn
authors.initials: B
authors.lastname: Heindryckx
authors.forename: Valérie
authors.initials: V
authors.lastname: Vernaeve
authors.forename: Rita
authors.initials: R
authors.lastname: Vassena
mesh_terms: D000818:Animals; D061207:Calcium Ionophores / Q000494:pharmacology; D005260:Female; D005306:Fertilization; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009865:Oocytes / Q000187:drug effects; D054801:Phosphoinositide Phospholipase C / Q000235:genetics* / Q000378:metabolism; D055101:Semen Analysis; D020554:Sperm Injections, Intracytoplasmic
chemical_list: D061207:Calcium Ionophores; C499235:PLCZ1 protein, human; D054801:Phosphoinositide Phospholipase C