Effect of calcium-modifying drugs on mouse in vitro fertilization and preimplantation development.

Calcium ions are required for normal in vitro fertilization and preimplantation development in the mouse. This study examined the effects of alterations in Ca2+ flux and distribution on sperm penetration of eggs and embryo cleavage. Compounds used included diltiazem, a Ca2+ channel blocker, and 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), an antagonist of intracellular calcium release. Incubation of sperm and eggs with diltiazem at 30 and 10 microM and TMB-8 at 30, 10, and 3 microM resulted in depressed fertilization compared with controls. Motility was not inhibited at these concentrations of either drug. Both drugs also depressed progression of mouse embryos from 2-cell to blastocyst at 30 and 3-microM concentrations. This study suggests that both Ca2+ flux and distribution to specific cellular sites are required for normal mouse in vitro fertilization and early preimplantation development.