OOCYTE ACTIVATION · Oocyte activation and human infertility: Identification and characterisation of a critical oocyte-borne receptor, and effects of laboratory procedures upon key proteins involved in oocyte activation

Oocyte activation and human infertility: Identification and characterisation of a critical oocyte-borne receptor, and effects of laboratory procedures upon key proteins involved in oocyte activation

The present project aimed at gaining new insights into the mechanisms underlying the activation of the mammalian oocyte. As widely known, mammalian oocytes are arrested at metaphase-II when ovulated and may only be released from this state when fertilised by a spermatozoon. Over years, the nature of the sperm protein accounting for oocyte activation was unknown and three different theories were proposed. However, over the last decade, mounting evidence has been supporting the crucial role of sperm-specific protein, phospholipase C ζ on the activation of the oocyte. In spite of this, other sperm proteins, such as post-acrosomal sperm protein (PAWP) have also been claimed to account for the activation of the oocyte. Because most of data supporting the role of PLCζ came from animal models, further research involving clinical samples was required. Against this background, the present project studied the presence and localization patterns of PLCζ in human sperm samples coming from fertile and non-fertile men, and found that the presence and localization patterns of PLCζ in human sperm are correlated to fertilisation rates following intracytoplasmic injection (ICSI). In contrast, proportions of sperm exhibiting PLCζ are not able to predict fertilising ability following conventional in vitro fertilisation (IVF). These data indicate that PLCζ may be used as a prognostic marker in specific cases of idiopathic infertility linked to male origin. This is a very important result, which emphasises the clinical relevance of this protein as the study conducted herein was that involved, thus far, the highest number of cases. Another part of the project was the study of how extrinsic and intrinsic factors could affect the localization patterns and expression of PLCζ. In this context, we found that iatrogenic damage could affect the localization of PLCζ. However, the most interesting result came from the evaluation of the relationship between advancing male age and expression and localization of PLCζ. While conventional spermiogram parameters such as motility were seen to be decreased concomitantly with advancing male age, no impact of age was observed on the proportions and expression of PLCζ. In conclusion, the present project has shown, by publishing their data in high impact factor journals, the relevance of the presence and localization patterns of PLCζ on the activation and fertilisation of the oocyte, and thus provides evidence for prognostic value of this protein. This may have a high impact upon the diagnostic tools of idiopathic infertility and may contribute to develop new therapeutic strategies for those men diagnosed with PLCζ deficiency. Given that, 1 in 7 couples suffer from infertility, the socio-economic impact of these findings is also high.

Data: CORDIS, © European Union