Identification of a hyaluronidase, Hyal5, involved in penetration of mouse sperm through cumulus mass

Kim, Ekyune; Baba, Daichi; Kimura, Masanori; Yamashita, Misuzu; Kashiwabara, Shin‐ichi; Baba, Tadashi

doi:10.1073/pnas.0506825102

Cited by 121 publications

(185 citation statements)

References 43 publications

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“…It is the hydrolytic enzymes released following the AR that ensure sperms to disperse the cumulus mass and reach the zona layer (Talbot, 1985;Yanagimachi, 1988). Unfortunately, this hypothesis is challenged by the observation that the expression of hydrolytic enzymes thought to facilitate sperm penetration of the cumulus, PH-20 and Hyal5, were found on the surface of sperm membrane but not within the acrosome (Lin et al, 1994;Kim et al, 2005;Kimura et al, 2009), which means sperm do not necessarily undergo AR to release hydrolytic enzymes when passing through the cumulus layer. Recent results obtained from PH-20 null mice have revealed that mouse sperm lacking PH-20 are still fertile with only delayed penetration through the cumulus (Baba et al, 2002), while sperm lacking both PH-20 and Hyal5 have not yet been studied.…”

Section: Status Of Sperm Acrosome In the Cumulus: The Controversymentioning

confidence: 97%

Acrosome reaction in the cumulus oophorus revisited: involvement of a novel sperm-released factor NYD-SP8

2011

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Fertilization is a process involving multiple steps that lead to the final fusion of one sperm and the oocyte to form the zygote. One of the steps, acrosome reaction (AR), is an exocytosis process, during which the outer acrosome membrane fuses with the inner sperm membrane, leading to the release of acrosome enzymes that facilitate sperm penetration of the egg investments. Though AR has been investigated for decades, the initial steps of AR in vivo, however, remain largely unknown. A well elucidated model holds the view that AR occurs on the surface of the zona pellucida (ZP), which is triggered by binding of sperm with one of the ZP glycosylated protein, ZP3. However, this model fails to explain the large number of 'falsely' acrosome-reacted sperms found within the cumulus layer in many species examined. With the emerging evidence of cross-talk between sperm and cumulus cells, the potential significance of AR in the cumulus oophorus, the outer layer of the egg, has been gradually revealed. Here we review the acrosome status within the cumulus layer, the cross-talk between sperm and cumulus cells with the involvement of a novel spermreleased factor, NYD-SP8, and re-evaluate the importance and physiological significance of the AR in the cumulus in fertilization.

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Section: Status Of Sperm Acrosome In the Cumulus: The Controversymentioning

confidence: 97%

Acrosome reaction in the cumulus oophorus revisited: involvement of a novel sperm-released factor NYD-SP8

2011

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“…The most common application is in ophthalmic surgery, in which it is used in combination with local anesthetics. Some bacteria, such as Staphylococcus aureus, Streptococcus pyogenes et pneumoniae and Clostridium perfringens, produce hyaluronidase as a means of increasing mobility through the body's tissues and as an antigenic disguise that prevents their recognition by phagocytes of the immune system (Ponnuraj and Jedrzejas, 2000;Lin and Stern, 2001;Lokeshwar et al, 2002;Hajjaji et al, 2005;Kim et al, 2005;Girish and Kemparaju, 2006).…”

Section: Degradationmentioning

confidence: 99%

Hyaluronic acid (hyaluronan): a review

Nečas¹,

Bartošíková²,

Brauner³

et al. 2008

Vet. Med.

838

646

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Hyaluronic acid (HA) is a high molecular weight biopolysacharide, discovered in 1934, by Karl Meyer and his assistant, John Palmer in the vitreous of bovine eyes. Hyaluronic acid is a naturally occurring biopolymer, which has important biological functions in bacteria and higher animals including humans. It is found in most connective tissues and is particularly concentrated in synovial fluid, the vitreous fluid of the eye, umbilical cords and chicken combs. It is naturally synthesized by a class of integral membrane proteins called hyaluronan synthases, and degraded by a family of enzymes called hyaluronidases. This review describes metabolisms, different physiological and pathological functions, basic pharmacological properties, and the clinical use of hyaluronic acid. Keywords: hyaluronic acid; metabolism; toxicityList of abbreviations CD44 = cell surface glycoprotein; CDC37 = intracellular HA-binding protein; Da = dalton; DNA = deoxynucleotid acid; ECM = extracellular matrix; EM = electron microscopy; GHAP = glial hyaluronate-binding protein; GIT = gastrointestinal tract; HA = hyaluronic acid; HARE = hyaluronic acid receptor for endocytosis; HAS1, HAS2, and HAS3 = types of hyaluronan synthases 1, 2 and 3; IHABP = intracellular HA-binding protein; IMP = integral membrane protein; IL-1 = interleukine 1; LM = light microscopy; LYVE-1 = lymphatic vessel endocytic receptor; MRHD = maximum recommended human dose; NS = normal saline; OA = osteoarthrosis; P-32 = protein-32; RHAMM = receptor for hyaluronic acid mediated mobility; RHAMM/IHABP = receptor for hyaluronic acid mediated mobility/intracellular HA-binding protein; TDLo = toxic dose low; TIMP-1 = tissue inhibitor of matrix metalloproteiness 1;TNF-α = tumor necrosis factor alpha; TSG-6 = tumor necrosis factor-α-stimulated gene-6; t 1/2 = half-life; UDP = uridine diphosphate

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“…The abundance of HA in the ECM is regulated by the local-regional balance between HA synthase activity and degradation by membrane-associated and lysosomal hyaluronidases. PH20 is unique as a membrane-bound, neutral active enzyme with high specific activity toward HA in vitro and in vivo, which is capable of degrading matrix-associated megadalton HA polymers to small tetrasaccharide and hexasaccharide products (16)(17)(18)(19). Given the rapid endogenous turnover of HA, accumulation in tumors could involve disequilibrium between the enzymes that synthesize HA and the enzymes that catabolize HA or receptors for cellular uptake, which subsequently mediate intracellular metabolism (20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Enzymatic Depletion of Tumor Hyaluronan Induces Antitumor Responses in Preclinical Animal Models

Thompson

Shepard²,

O’Connor³

et al. 2010

Molecular Cancer Therapeutics

257

278

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Hyaluronan (HA) is a glycosaminoglycan polymer that often accumulates in malignancy. Megadalton complexes of HA with proteoglycans create a hydrated connective tissue matrix, which may play an important role in tumor stroma formation. Through its colloid osmotic effects, HA complexes contribute to tumor interstitial fluid pressure, limiting the effect of therapeutic molecules on malignant cells. The therapeutic potential of enzymatic remodeling of the tumor microenvironment through HA depletion was initially investigated using a recombinant human HA-degrading enzyme, rHuPH20, which removed HA-dependent tumor cell extracellular matrices in vitro. However, rHuPH20 showed a short serum half-life (t 1/2 < 3 minutes), making depletion of tumor HA in vivo impractical. A pegylated variant of rHuPH20, PEGPH20, was therefore evaluated. Pegylation improved serum half-life (t 1/2 = 10.3 hours), making it feasible to probe the effects of sustained HA depletion on tumor physiology. In high-HA prostate PC3 tumors, i.v. administration of PEGPH20 depleted tumor HA, decreased tumor interstitial fluid pressure by 84%, decreased water content by 7%, decompressed tumor vessels, and increased tumor vascular area >3-fold. Following repeat PEGPH20 administration, tumor growth was significantly inhibited (tumor growth inhibition, 70%). Furthermore, PEGPH20 enhanced both docetaxel and liposomal doxorubicin activity in PC3 tumors (P < 0.05) but did not significantly improve the activity of docetaxel in low-HA prostate DU145 tumors. The ability of PEGPH20 to enhance chemotherapy efficacy is likely due to increased drug perfusion combined with other tumor structural changes. These results support enzymatic remodeling of the tumor stroma with PEGPH20 to treat tumors characterized by the accumulation of HA. Mol Cancer Ther; 9(11); 3052-64. ©2010 AACR.

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Identification of a hyaluronidase, Hyal5, involved in penetration of mouse sperm through cumulus mass

Cited by 121 publications

References 43 publications

Acrosome reaction in the cumulus oophorus revisited: involvement of a novel sperm-released factor NYD-SP8

Acrosome reaction in the cumulus oophorus revisited: involvement of a novel sperm-released factor NYD-SP8

Hyaluronic acid (hyaluronan): a review

Enzymatic Depletion of Tumor Hyaluronan Induces Antitumor Responses in Preclinical Animal Models

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