Sperm Factors and Oocyte Activation: Current Controversies and Considerations1

Abstract

The beginning of embryogenesis is preceded by a sequence of events mediated by the release of intracellular calcium in the ooplasm, a multifaceted process known as oocyte activation. It is now well established that a sperm protein factor introduced into the oocyte at the time of gamete fusion is responsible for initiating the cascade of signaling events involved. Several sperm proteins have been hypothesized as the sperm oocyte-activating factor (SOAF) over the years, with phospholipase C zeta 1 (PLCZ1 or PLCzeta) emerging as the strongest candidate. A large body of consistent and reproducible evidence, from both biochemical and clinical settings, has accumulated in support of PLCzeta, and data clearly demonstrate that oocyte activation ability can be rescued in PLCzeta-deficient sperm by either PLCzeta cRNA or recombinant PLCzeta protein. However, a series of recent publications has challenged the dominance of PLCzeta and proposed an alternative candidate protein, WBP2 N-terminal like (WBP2NL or PAWP). These events have led to significant debate, fueled by the opposing views of two independent laboratories, each defending its own respective SOAF candidate. This raises important questions with regards to the relative importance of these two proteins in diagnostic and therapeutic medicine, and invites urgent research attention. Here, it is our intention to reflect upon this now very controversial area in order to engage the scientific and clinical communities in addressing the true importance of these two sperm proteins.

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

“…Failed fertilization post-ICSI is attributed to the lack or deficiency of sperm-associated oocyte-activating factors (SOAF) (Amdani et al, 2015). SOAF(s) compartmentalize as part of the post-acrosomal sheath of sperm perinuclear theca (PAS-PT) and trigger intracellular Ca 2+ -release upon fusion of spermatozoa/oocyte membranes or insemination of spermatozoa into oocyte (Sutovsky et al 2003).…”

“…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).…”

Aide à l’activation ovocytaire

“…Une hypothèse reposerait sur la possibilité d'une liaison de la phospholipase C gamma (PLCγ) à une protéine ovocytaire YAP (yes-associated protein) qui interagirait avec le domaine SH3 (SRC homology 3 domain) de la PLCγ, permettant la synthèse d'IP 3 ( Figure 2). Cependant cette hypothèse reste controversée [4]. En effet, d'autres chercheurs n'arrivent pas à obtenir de telles oscillations calciques avec PAWP [15].…”

“…Ces oscillations seraient déclenchées par un facteur cytosoluble d'origine spermatique, libéré dans le cytoplasme ovocytaire au moment de la fusion des gamètes. Les Anglo-Saxons utilisent le terme SOAF pour sperm oocyte-activating factor, mais l'identité de ce facteur est restée élusive durant de nombreuses années [4]. En 2002, on a proposé la phospholipase C Zeta (PLCζ), une protéine qui chez les mammifères est exclusivement exprimée dans les spermatozoïdes [5].…”

Contrasting effects of heat shock during in vitro maturation on development of in vitro‐fertilized and parthenogenetic bovine embryos

“…Some sperm factors, such as PLC zeta 1 and post-acrosomal WW-domain binding protein, are considered to play an important role in oocyte activation (Amdani, Yeste, Jones, & Coward, 2015;Ross et al, 2008;Yeste, Jones, Amdani, & Coward, 2017). Sperm can also deliver microRNAs or mRNAs to the fertilized oocyte and influence further embryo development (Boerke, Dieleman, & Gadella, 2007;Hamatani, 2012).…”