Cell volume regulation in mammalian oocytes and preimplantation embryos

The earliest stages of preimplantation embryos are particularly sensitive to increased osmolarity, even within the physiological range. This sensitivity contributed to persistent developmental arrest, even when embryos were cultured in vitro in older, conditioned culture media, and seems to arise when embryos at the 1- and 2-cell stages accumulate inorganic ions used for cell volume homeostasis at too high a level, through activation of coupled Na+/H+ and HCO?3-/Cl- exchange. Such accumulation of inorganic ions can be disruptive since, above a certain level, the increased ionic strength disrupts cellular biochemistry and macromolecular functions and alters membrane potential. To counter this, embryos have evolved mechanisms of cell volume regulation that are unique to early preimplantation embryogenesis. The primary role of these is glycine accumulation via the GLYT1 transporter, with a secondary contribution by betaine accumulation via the SIT1 transporter. Independent cell-volume regulation first arises in the oocyte only after ovulation is triggered, when the strong oocyte-zona pellucida adhesion present in germinal vesicle stage oocytes in the ovarian follicle is released and GLYT1 becomes activated to begin accumulating glycine. Open questions still remain regarding how these processes are regulated. Mol. Reprod. Dev. 79: 821831, 2012. (C) 2012 Wiley Periodicals, Inc.