Distinct pathways drive anterior hypoblast specification in the implanting human embryo.

Development requires coordinated interactions between the epiblast, which generates the embryo proper; the trophectoderm, which generates the placenta; and the hypoblast, which forms both the anterior signalling centre and the yolk sac. These interactions remain poorly understood in human embryogenesis because mechanistic studies have only recently become possible. Here we examine signalling interactions post-implantation using human embryos and stem cell models of the epiblast and hypoblast. We find anterior hypoblast specification is NODAL dependent, as in the mouse. However, while BMP inhibits anterior signalling centre specification in the mouse, it is essential for its maintenance in human. We also find contrasting requirements for BMP in the naive pre-implantation epiblast of mouse and human embryos. Finally, we show that NOTCH signalling is important for human epiblast survival. Our findings of conserved and species-specific factors that drive these early stages of embryonic development highlight the strengths of comparative species studies.

Human recombinant hyaluronidase (Cumulase) improves intracytoplasmic sperm injection survival and fertilization rates.

The cumulus-corona-oocyte complex, composed of cumulus granulosa cells embedded in a matrix of hyaluronan oligosaccharide chains cross-linked by hyaluronan binding proteins and proteoglycans, surrounds each oocyte and must be removed prior to intracytoplasmic sperm injection (ICSI). This is traditionally achieved using enzymatic digestion of the matrix with a bovine-derived hyaluronidase followed by mechanical denudation through pipetting. A human recombinant hyaluronidase (Cumulase) has been developed with the intent of circumventing the problems and concerns associated with the animal origin and lack of purity of the bovine-derived form of the enzyme. In order to compare the effect of Cumulase with that of the bovine enzyme on the rates of normal fertilization and oocyte damage, a retrospective study using four experienced practitioners was performed. In 2006, using Cumulase, a significantly increased rate of normal fertilization (P = 0.0003) and a significantly decreased rate of oocyte damage (P < 0.0001) were observed compared with 2005, during which time bovine-derived hyaluronidase was predominantly used. This study indicates that Cumulase is safe and effective for use in the removal of the cumulus-corona-oocyte complex prior to ICSI, and may have several distinct advantages over the animal-derived form of the enzyme in terms of safety and efficacy.