Bernhardt 2015 Abstract MiPschool Greenville 2015

Regulation of Ca2+ entry during oocyte maturation and following fertilization.

Link:

Bernhardt ML, Padilla-Banks E, Zhang Y, McDonough CE, Miao YL, Williams CJ (2015)

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 

Organism: Mouse 

Event: Poster 

Affiliations

Reproductive Developm Biol Lab, Nat Inst Health, Nat Inst Health, Research Triangle Park, NC, USA. - miranda.bernhardt@nih.gov