Hyal3: Redefined as a Reproductive Hyaluronidase

Fertilization in mammals requires the successful completion of cumulus cell dispersion, zona pellucida binding, and perivitelline space penetration. The digestion of hyaluronan, abundant in the cumulus matrix and zona pellucida, is essential for permeating the vestment of the oocyte and is performed by reproductive hyaluronidases. HYAL3/Hyal3, located on human chromosome 3p21/mouse 9F1 and previously thought to be a somatic hyaluronidase, shares great similarity to reproductive hyaluronidases, yet there have been no studies to document a role in fertilization. Recently it has been shown that sperm lacking functional Spam1 are able to penetrate an oocyte, indicating related hyaluronidases can functionally contribute to fertilization. Interestingly, humans lack a functional reproductive hyaluronidase other than SPAM1. Hyal3 has the highest amino acid identity to its human homolog and shares high testicular expression as SPAM1. Therefore, it is important to investigate the potential role in the fertilization process of humans in addition to or absence of a functional SPAM1 protein. Here, we demonstrate that Hyal3 is also present on the head of sexually mature sperm and is involved in acrosomal exocytosis. Hyal3 is also present in the epididymis and uterine luminal fluid of females in estrus. Based on the tissue expression patterns of Hyal3, its functional domain similarities, and involvement in acrosomal exocytosis, a redefinition of this protein is in order.