A Short-Chain Analogue of Seminolipid: Synthesis and Inhibitory Effect on Mouse Fertilization.

Seminolipid (sulfogalactosylglycerolipid (SGG)) is abundantly present on the sperm surface and its roles in sperm-egg interaction are well-documented. SGG liposomes have direct affinity for the zona pellucida (ZP), the egg extracellular matrix. SGG is also integral to the formation of sperm lipid rafts, which are platforms on the sperm surface for ZP binding. Our objective was to chemically synthesize a short-chain analog of SGG (SC-SGG with a C6 acyl chain instead of C16 in the natural lipid), which is solubilized in an aqueous environment, and to determine the inhibitory effects of SC-SGG in mouse sperm-egg interaction, and thus fertilization. SC-SGG was synthesized from a 3--galactopyranosyl--glycerol intermediate protected on the sugar moiety through the acylation of glycerol with caproic acid, deprotection and regioselective 3--sulfation of the galactose residue. SC-SGG solubilized in a medium was used to treat sperm-egg co-incubates or to pretreat sperm or eggs before co-incubating sperm with eggs or vice versa. Sperm-ZP binding and fertilization (scoring eggs with two pronuclei) were microscopically assessed. SC-SGG was efficiently synthesized with a 78% overall yield. SC-SGG inhibited sperm-ZP binding and fertilization of mouse gametes in a concentration-dependent manner, and at 6 µM SC-SGG, the mouse fertilization was zero. SC-SGG inhibited the fertilizing ability of both sperm and eggs, as shown in the pretreatment experiments. SC-SGG was an effective inhibitor of mouse fertilization in vitro. It warrants development to be a non-hormonal contraceptive.