Maturation of cortical endoplasmic reticulum clusters in the mouse oocyte: changes at fertilization

Oocytes from many invertebrate and vertebrate species exhibit unique endoplasmic reticulum specializations (cortical ER clusters) thought be essential for egg activation. In examination of cortical ER clusters, we observed they were tethered to previously unreported fenestrae within the cortical actin layer. Further, studies demonstrated sperm preferentially bind to plasma membrane overlying the fenestrae, establishing close proximity to underlying ER clusters. Moreover, following sperm-oocyte fusion, cortical ER clusters undergo a previously unrecognized global maturational change in volume, shape, and calreticulin content that persists through sperm incorporation, before dispersing at the pronuclear stage. These changes did not occur in oocytes from females mated with Izumo1 -/- males demonstrating that gamete fusion plays an important role in ER cluster maturation. In addition to these global changes seen at sites distant to the sperm, highly localized ER modifications were noted at the sperm binding site as cortical ER clusters surround the sperm head during incorporation, then form a diffuse cloud surrounding the decondensing sperm nucleus. This study provides the first evidence that cortical ER clusters interact with the fertilizing sperm, indirectly through a previous unknown lattice work of actin fenestrae, then directly during sperm incorporation. These observations raise the possibility that oocyte ER cluster-sperm interactions provide a competitive advantage to the oocyte, which may not occur during assisted reproductive technologies such as intracytoplasmic sperm injection. Summary Statement Sperm-oocyte interactions stimulate global changes in cortical endoplasmic reticulum cluster structure as well as localized responses at the sperm binding site.