Lipid rafts: keys to sperm maturation, fertilization, and early embryogenesis

Abstract

Cell membranes are composed of many different lipids and protein receptors, which are important for regulating intracellular functions and cell signaling. To orchestrate these activities, the cell membrane is compartmentalized into microdomains that are stably or transiently formed. These compartments are called "lipid rafts". In gamete cells that lack gene transcription, distribution of lipids and proteins on these lipid rafts is focused during changes in their structure and functions such as starting flagella movement and membrane fusion. In this paper, we describe the role of lipid rafts in gamete maturation, fertilization, and early embryogenesis.

Figure 1

Schematic of lipid rafts in gamete formation, function, fertilization, and early embryogenesis. (a) Sperm mature, gaining motility and fertilizing abilities, during epididymis transit. The extracellular factors, epididymosome and HE1, dynamically change the components of the sperm plasma membrane. (GPI, glycosylphoshphatidylinositol; SM, sphingomyelin; PFA, polyunsaturated membranous fatty acids). (b) Ejaculated sperm are temporally bound to SVS2 (decapacitation). SVS2 binds to GM1 of the sperm head in the uterus, resulting in the inhibition of the fertilizing ability of sperm. Subsequently, the sperm that migrate to the oviduct undergo capacitation. Capacitation causes an efflux of cholesterol and G_M1 from the plasma membrane and an increase of membrane fluidity and protein tyrosine phosphorylation (PTP). (c) Sperm recognize and adhere to UpIII/UpIb of Xenopus oocyte and fuse with CD9/CD81 of murine oocyte plasma membrane. These molecules are enriched in lipid rafts, and oocytes treated with cyclodextrin prevent the sperm from fertilization. (d) In early embryogenesis, SSEAs are colocalized with cholesterol and G_M1 plays an important role in the compaction of an embryo, leading to the decision of cell fate and its pluripotency.

Figure 2

Distribution of cholesterol during sperm maturation in murine epididymis. (a) Sperm collected from caput epididymis reveal filipin signal on the whole head. After epididymal transit (cauda epididymis), the signal is not detected in the postacrosomal region (PA). Scale bar = 5 μm. (b) Densitometric analysis shows a significant decrease of filipin signal at the postacrosomal region. AA, apical acrosome; ES, equatorial segment; PA, postacrosomal.

Figure 3

Distribution and function of CD9 and CD81 in murine oocyte. (a) The distribution of CD9 (green) is distinct from that of CD81 (red). CD9 localizes over the entire surface membrane, except for the MII plate, whereas CD81 shows patches with a low frequency. Scale bar = 10 μm. (b) Cell surface-bound sperm shows colocalization of CD9 and CD81 with sperm nuclei (blue). Scale bar = 10 μm. (c) Pretreatment of an oocyte with cyclodextrin (CD) prevents sperm from fusing and fertilizing the oocyte. The same phenomenon is observed in the treatment of filipin.