inositol-1-4-5-trisphosphate and Infertility

We have discovered that a single sperm protein, phospholipase C-zeta (PLCζ), can stimulate intracellular Ca(2+) signalling in the unfertilized oocyte ('egg') culminating in the initiation of embryonic development. Upon fertilization by a spermatozoon, the earliest observed signalling event in the dormant egg is a large, transient increase in free Ca(2+) concentration. The fertilized egg responds to the intracellular Ca(2+) rise by completing meiosis. In mammalian eggs, the Ca(2+) signal is delivered as a train of long-lasting cytoplasmic Ca(2+) oscillations that begin soon after gamete fusion and persist beyond the completion of meiosis. Sperm PLCζ effects Ca(2+) release from egg intracellular stores by hydrolyzing the membrane lipid PIP(2) and consequent stimulation of the inositol 1,4,5-trisphosphate (InsP(3) ) receptor Ca(2+) -signalling pathway, leading to egg activation and early embryogenesis. Recent advances have refined our understanding of how PLCζ induces Ca(2+) oscillations in the egg and also suggest its potential dysfunction as a cause of male infertility.

Topics: Animals; Calcium; Calcium Signaling; Embryonic Development; Female; Fertilization; Humans; Infertility; Inositol 1,4,5-Trisphosphate; Male; Meiosis; Mice; Oocytes; Phosphoinositide Phospholipase C; Pregnancy; Sperm-Ovum Interactions; Spermatozoa

Signals from germ and myoepithelial sheath cells initiate ovulation in Caenorhabditis elegans. The coordinated dilation and contraction of spermatheca lead to subsequent fertilization of oocyte. Either the dominant negative mutant pat-3 beta integrin or disruption of talin expression block ovulation. Talin loss-of-function uncovers roles in cell contractility and migration in C. elegans. Role of beta pat-3 integrins in development and function of Caenorhabditis elegans muscles and gonads, suggesting that the interaction between the cell and the extracellular matrix (ECM) is also important for ovulation. Here, we report that integrin plays an essential role in fertility via IP(3) signaling. Sterility caused by RNAi of pat-3 and ECM molecules was suppressed by increased IP(3) signaling. Our data suggest that the cell-ECM interaction controls ovulation via IP(3) signaling.

Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Calcium Channels; Extracellular Matrix; Fertility; Gonads; Infertility; Inositol 1,4,5-Trisphosphate; Inositol 1,4,5-Trisphosphate Receptors; Integrin beta Chains; Ovulation; Phospholipase C gamma; Receptors, Cytoplasmic and Nuclear; RNA Interference; RNA, Small Interfering; Signal Transduction; Type C Phospholipases