Human Contraceptives: Current Status, Sperm Antigen Inhibitors and an Insight into PCSK4

Abstract

Rapid growth of global human population has been implicating to food shortage, social problems and environmental degradation. Contraceptive devices have long been applied as a major method to reduce natality. Current application of this technology relies upon hormonal administration, condom, withdrawal and recently hormonal vaccino-contraceptive. Discoveries of antisperm proteins have been directing current researches toward developments of antisperm antibody (ASA) contraceptions. Actions of ASA are targeting antigens either on the head or on the tail of sperm. Antibodies targeting head antigens aimed at blocking gamete fusion, ZP penetration and/or acrosome reaction. Molecules working on sperm tails are aimed to block sperm motility or energy production. PCSK4 is one sperm antigen firstly expressed on the human sperm acrosome during its initial development on the round spermatid and retains on the acrosome until sperm is matured. It is known to contribute to the postcapacitational hyperactivation of sperm essential for zona penetration. Rat models injected with rabbit-anti human PCSK4 developed incompetent sperm and allowance of these male rats to fertile female rats resulted significant reduction of conception rate. Apart from antibody, synthetic inhibitors of PCSK4 have also been developed. Future developments of ASA contraception are discussed.