Role of zona pellucida glycoproteins during fertilizationin humansSatish

Abstract

tIn the last decade, scientific investigations pertaining to the role of zona pellucida (ZP) gly-coproteins during fertilization in humans have led to new insights. This has been achievedusing purified native/recombinant human zona proteins and transgenic mice expressinghuman ZP glycoproteins. The proposed model in mice of ZP glycoprotein-3 (ZP3) actingas primary sperm receptor and ZP glycoprotein-2 (ZP2) as secondary sperm receptor hasbeen modified for sperm–egg binding in humans. ZP glycoprotein-1 (ZP1), ZP3, and ZPglycoprotein-4 (ZP4) have been shown to bind to the capacitated human sperm. ZP2 bindsto the acrosome-reacted human spermatozoa. Further, the eggs obtained from transgenicmice expressing human ZP2 alone or in conjunction with other human instead of mousezona proteins showed binding of human sperm, suggesting that ZP2 might also play a rolein sperm–egg binding. This function has been mapped to a domain corresponding to aminoacid residues 51–144 of ZP2. In contrast to mice, where ZP3 is the primary agonist for induc-ing the acrosome reaction, in humans, the acrosome reaction can be mediated by ZP1, ZP3,and ZP4. The effect of mutations in the genes encoding zona proteins on the ZP morphol-ogy and infertility has not been established. Further, the role of autoantibodies against ZPin women with ‘unexplained infertility’ leading to poor outcome of in vitro fertilization iscurrently controversial and needs further investigations. Understanding the role of ZP gly-coproteins during human fertilization facilitates the development of new contraceptivesand strategies to overcome the problem of infertility.