Bernhardt 2015 Abstract MiPschool Greenville 2015
|Regulation of Ca2+ entry during oocyte maturation and following fertilization.|
Event: MiPschool Greenville 2015
Activation of mammalian embryonic development relies on a series of fertilization-induced increases in intracellular Ca2+. Full egg activation also requires influx of extracellular Ca2+, but the channel or channels mediating this influx remain unknown. In these studies we examined whether T-type Ca2+ channels, including CACNA1H subunit-containing CaV3.2 channels, mediate Ca2+ entry after fertilization. We found that female mice lacking CACNA1H have reduced litter size. Careful analysis of Ca2+ oscillation patterns following in vitro fertilization (IVF) of Cacna1h-/- eggs revealed shortening of the first Ca2+ transient length and reduction in Ca2+ oscillation persistence. Both total and endoplasmic reticulum (ER) Ca2+ stores in Cacna1h-/- eggs were reduced, showing an impairment of Ca2+ accumulation during oocyte maturation in Cacna1h-/- eggs. Pharmacological inhibition of T-type channels during in vitro maturation also reduced Ca2+ store accumulation, indicating that T-type channels are responsible for mediating Ca2+ entry and ER store accumulation during meiotic maturation. T-type channel inhibition also reduced oscillation persistence, frequency, and duration following IVF in wild-type eggs. Together, these data support previously unrecognized roles for T-type Ca2+ channels in mediating the maturation-associated increase in ER Ca2+ stores and allowing Ca2+ influx required for the activation of embryo development. In future studies, we plan to investigate how fluxes in oocyte Ca2+ and Zn2+ influence mitochondrial function, which is a critical determinant of oocyte and embryo quality. Developing better understanding of the interplay between these pathways may translate into clinical application to improve assisted reproductive technologies.
• O2k-Network Lab: CN Tianjin Zhang Y
Labels: MiParea: Developmental biology
Reproductive Developm Biol Lab, Nat Inst Health, Nat Inst Health, Research Triangle Park, NC, USA. - [email protected]