Human zona pellucida (ZP) matrix is composed of four
glycoproteins designated as ZP
glycoprotein -1 (ZP1), -2 (ZP2), -3 (ZP3), and -4 (ZP4). Mutations in the genes encoding human ZP
glycoproteins are one of the causative factors leading to abnormal ZP matrix and
infertility in women. Relevance of the human ZP
glycoproteins in 'sperm-oocyte' binding has been delineated by using either transgenic animal models expressing human
zona proteins or purified native/recombinant human
zona proteins. Studies based on the purified native/recombinant human
zona proteins revealed that ZP1, ZP3, and ZP4 primarily bind to the capacitated acrosome-intact human spermatozoa whereas ZP2 binds to acrosome-reacted spermatozoa. On the contrary, human spermatozoa binds to the eggs obtained from transgenic mouse lines expressing human ZP2 but not to those expressing human ZP1, ZP3, and ZP4 suggesting that ZP2 has an important role in human 'sperm-oocyte' binding. Further studies using transgenic mouse lines showed that the N-terminus of human ZP2 mediate the taxon-specific human sperm-oocyte binding. Both
glycans and
protein-
protein interactions have a role in human gamete interaction. Further studies have revealed that the purified native/recombinant human ZP1, ZP3, and ZP4 are competent to induce acrosome reaction. Human sperm binds to the mouse transgenic eggs expressing human ZP1-4 instead of mouse ZP1-3
proteins, penetrated the ZP matrix and accumulated in the perivitelline space, which were acrosome-reacted suggesting that human ZP2 in transgenic mouse model also induce acrosome reaction. In humans N-linked glycosylation of
zona proteins have been shown to play an important role in induction of the acrosome reaction. Hence in humans, based on studies using transgenic mouse model as well as purified native/recombinant
zona proteins, it is likely that more than one
zona protein is involved in the 'sperm-oocyte' binding and induction of the acrosome reaction.