Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.36 (hyaluronidase)
4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acrosin and acrosomal hyaluronidase were inhibited by tetradecyl sodium sulphate (TDSS) in vitro at concentrations of less than 10(-4) M. TDSS prevented the removal in vitro of the cumulus oophorus by testicular hyaluronidase and the zona pellucida by acrosin. TDSS had a contraceptive effect in rabbits when administered intravaginally before coitus or released at levels of 1-3 micrograms/day from intrauterine silicone rubber devices.
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PMID:Antifertility effects of tetradecyl sodium sulphate in rabbits. 634 64

A study was designed to determine whether tetradecyl sodium sulfate (TDSS), a potent inhibitor of both acrosin and hyaluronidase, would have a contraceptive effect in rabbits when a controlled level of TDSS was released from a vaginal delivery system over a 4-week period. The toroidal shaped delivery system was composed of a core of TDSS incorporated in polyurethane surrounded by a rate-limiting membrane of polyurethane. These devices were found to have a sustained in vitro TDSS release rate of equal to or greater than 400 mcg/day for over 30 days and had a complete contraceptive effect in 15 rabbits bred weekly for 4 weeks. No toxic effects were noted at 20 mg/day doses, but slight to moderate vaginal irritation was observed in the 50 and 100 mg/day groups. These results clearly demonstrate that TDSS is a useful intravaginal contraceptive agent when incorporated in a delivery system that continuously releases the compound into the vagina. 175 corpora lutea were found in the ovaries of the study rabbits, indicating that TDSS has no effect on ovulation. It remains unknown whether the TDSS binds to all the spermatozoa at the point of TDSS release in the vagina or whether some TDSS finds its way into the oviduct after release into the vagina and finally binds there to the few spermatozoa that reach this site. The vaginal delivery system shown in this study to be efficacious in rabbits could lead to the development of a similar device for human contraception. The advantages of this system are that it frees users from daily or postcoital administration, is capable of self-insertion, and uses a nonhormonal agent as the active ingredient.
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PMID:An intravaginal contraceptive device for the delivery of an acrosin and hyaluronidase inhibitor. 636 1

The effect of in vitro capacitation (events that occur before the acrosome reaction) on the acrosomal enzymes of human spermatozoa was determined. Capacitation of human spermatozoa was assessed by their ability to penetrate denuded hamster oocytes. The activities of a number of enzymes commonly associated with the sperm acrosome, including nonzymogen acrosin, proacrosin, inhibitor-bound acrosin, hyaluronidase, acid phosphatase, beta-glucuronidase, beta-glucosidase, beta-N-acetylglucosaminidase, beta-galactosidase and beta-N-acetylgalactosaminidase were assessed. With the exception of acid phosphatase, no alteration in enzyme activity occurred after 4 h of incubating the spermatozoa under capacitation conditions although gamete fusion took place. The acid phosphatase levels decreased twofold, presumably due to the loss of seminal (prostatic acid phosphatase that loosely adheres to spermatozoa. After 8 h of capacitation, a large decrease in sperm enzyme levels took place only in the case of hyaluronidase, although small decreases were also noted in total acrosin, proacrosin and inhibited acrosin. No new electrophoretically migrating forms of acrosin were observed. Decreases in total acrosin and proacrosin, but not in inhibited acrosin, also occurred when spermatozoa were incubated under noncapacitating conditions for 8 h, indicating that capacitation may specifically cause the release of some acrosin inhibitor from human spermatozoa. It is concluded that, with the possible exception of hyaluronidase, the in vitro capacitation of human spermatozoa does not cause a major change in its acrosomal enzyme content so that these hydrolases are fully present before the acrosome reaction takes place during gamete fusion. Serum albumin appears to protect against the loss of some of these enzymes since the activity of several glycosidases was significantly reduced when the spermatozoa were incubated for 8 h in human serum albumin-free medium.
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PMID:Acrosomal enzymes of human spermatozoa before and after in vitro capacitation. 640 71

Histochemical procedures for the mouse sperm enzymes hyaluronidase, esterase and acrosin were used to test the inhibitory effects of the low molecular weight hyaluronidase inhibitor sodium aurothiomalate (Myocrisin): hyaluronidase and esterase, but not acrosin, were inhibited. These enzymes were also inhibited in testis homogenates when assayed spectrophotometrically. These results suggest that the antifertility effects of sodium aurothiomalate may be due to the inhibition of several sperm enzymes including both hyaluronidase and esterase. These histochemical assays may be useful for in-vivo detection of chemicals that affect male fertility.
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PMID:Histochemical evaluation of sodium aurothiomalate inhibition of mouse sperm enzymes. 642 May 52

This article reviews new advances in biochemistry, biotechnology, and immunology relevant to antifertility vaccine development and evaluates the current status and future prospects of contraceptive vaccines and other immunologic approaches to fertility regulation. Contraceptive vaccine candidates include human chorionic gonadotropin, human luteinizing hormone and luteinizing hormone releasing hormone, and reproductive steroid hormones. Sperm enzymes are attractive for a contraceptive vaccine; among the sperm antigens studied are antibodies to hyaluronidase, acrosin, and lactate dehydrogenase-C4. Several laboratories have developed monoclonal antibodies to a variety of sperm antigens and are using them to identify and characterize new sperm proteins and their roles in fertility. Considerable progress has been made toward biochemical characterization of unique glycoproteins constituting the zona pellucida. Zona pellucida antigens are good candidates because antizona antibodies may block both fertilization and implantation, and low amounts of antibody would be sufficient because of the small number of mature eggs with zona present at any time. Studies are underway to identify human embryonic antigens through examination of the protein profile of human teratocarcinoma cell lines at various stages of differentiation and through analysis of antibodies in human pregnancy and infertility sera. Placental and extraembryonic membranes produce several tissue-specific antigens that have been considered for antifertility vaccines, but concern that they could produce late or incomplete abortion has prevented their serioud consideration. Because of possibly serious systemic side effects, presence of the blood-testis barrier, and large number of sperm produced daily, it is unlikely that sperm vaccines can be safely administered to men. Nautural protective mechanisms will probably render some immunocontraceptive approaches ineffective. The possibility of serious pathogenic side effects of contraceptive vaccines demands vaccines demands a cautious approach to their development.
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PMID:A new look at antifertility vaccines. 657 34

Ovulated opossum oocytes are surrounded by a zona pellucida, but not by cumulus cells. Opossum sperm carry at least four acrosomal hydrolases (hyaluronidase, acrosin, N-acetylhexosaminidase, and arylsulfatase); the functions of these enzymes in opossum fertilization are uncertain. To identify possible substrates for these hydrolases, the ultrastructure of opossum oocytes was examined after fixation in the presence of ruthenium red which stabilizes extracellular matrices. This oocyte is unusual in having a wide perivitelline space containing a highly structured extracellular matrix (ECM). The ECM is comprised of granules and filaments, and it resembles matrices known to contain hyaluronic acid in other systems. Hydrolases, known to be present in opossum acrosomes, were tested for their effect on the ultrastructure of the zona pellucida and matrix of the perivitelline space. Trypsin dissolved the zona pellucida and decreased the size of the granules in the perivitelline space. Streptomyces hyaluronidase, which specifically attacks hyaluronic acid, removed only matrix filaments. Arylsulfatase, N-acetylhexosaminidase, and beta-glucuronidase did not affect the zona pellucida or ECM in our assay. These observations are consistent with the ideas that (1) opossum sperm must penetrate two oocyte investments, the zona pellucida and ECM of the perivitelline space; (2) the ECM contains hyaluronic acid (filaments) and protein (granules); (3) opossum sperm acrosin may function in penetration of the zona pellucida and ECM; and (4) opossum sperm hyaluronidase may function in penetration of the ECM by degrading hyaluronic acid (filaments). Dissolution of the granules and filaments from oocyte microvilli is probably necessary to permit close apposition and fusion of the sperm and oocyte membranes. The evolutionary significance of these results is discussed.
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PMID:Ultrastructure of opossum oocyte investing coats and their sensitivity to trypsin and hyaluronidase. 671 16

Pronase-resistant low molecular weight stimulators for the activation of proacrosin to acrosin were found in rhesus monkey oviduct fluid collected before, during and after ovulation, but the presence of high concentrations of acrosin inhibitors before and after ovulation partly masked the stimulation in unfractionated fluid. This low molecular weight fraction of oviduct fluid had no detectable esterase or amidase activity by itself, and the stimulating factors were sensitive to digestion by hyaluronidase and chondroitin ABC lyase and were presumed to be glycosaminoglycans. Heparin and hyaluronic acid had similar effects. The presence of soluble glycosaminoglycans at the site of fertilization suggests that they may have a role in capacitation and fertilization.
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PMID:Stimulation of rhesus monkey (Macaca mulatta) proacrosin activation by oviduct fluid. 700 Oct 8

A high molecular weight antifertility factor (AF-1) was obtained in a high degree of purity from human seminal plasma by ultracentrifugation, CM-cellulose and concanavalin A chromatography, and Sepharose 6B gel filtration. A final purification step involving preparative disc electrophoresis was occasionally required. AF-1 showed a dose-dependent inhibition of the in vitro fertilizing ability of capacitated mouse spermatozoa, causing 50% inhibition of fertilization at approximately 27.5 micrograms/10(6) spermatozoa. Removal of the follicle cell layer of the oocyte did not decrease the antifertility effect of AF-1 but inhibition of fertilization was no longer observed after dispersal of the zona pellucida. The effect of AF-1 was on the spermatozoa and not on the oocytes. These results show that AF-1 treatment prevents capacitated spermatozoa from penetrating the zona pellucida and possibly the follicle cell layer. The mechanism by which AF-1 does so is not known because AF-1 did not prevent the in vitro acrosome reaction of guinea pig spermatozoa, nor did it inhibit the activity of human acrosin or bovine testicular hyaluronidase. The antifertility activity of AF-1 is reversed after recapacitation of the AF-1 treated spermatozoa and it can be assumed that AF-1 is either dissipated or loses activity during the transport of the spermatozoa through the female genital tract when capacitation takes place. AF-1 is heat labile. The properties of AF-1 are the same as those found previously for the pellet obtained by high-speed centrifugation of human seminal plasma, indicating that this is the primary, nonparticulate, high molecular weight factor with antifertility activity in human semen.
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PMID:Properties of a highly purified antifertility factor from human seminal plasma. 715 55

The effects of ingestion of sodium fluoride (NaF), 10 mg/kg body weight for 50 days, on the structure and metabolism of sperm of albino rats (Rattus norvegicus), were investigated. In different groups of rats, the reversible effects upon withdrawal of NaF treatment and by administering some therapeutic agents, viz., ascorbic acid and calcium alone and in combination with NaF (50 and 70 days), on sperm structure and metabolism were also studied. The results revealed that the sperm acrosomal hyaluronidase and acrosin were reduced after 50 days of NaF treatment. Sperm stained with acidic alcoholic silver nitrate revealed acrosomal damage and deflagellation, which might be causative factors for the reduced activity of the enzymes. These alterations also resulted in a decline in sperm motility. The cauda epididymal sperm count was decreased, perhaps because of spermatogenic arrest. Thus, the low sperm motility and count ultimately contributed toward reduction in fertility by NaF treatment. However, withdrawal of NaF treatment for 70 days produced incomplete recovery, while administration of ascorbic acid and calcium, individually and in combination, brought about significant recovery of fluoride-induced effects. Thus, the effects of fluoride on sperm structure and metabolism of rats are transient and reversible.
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PMID:Reversible effects of sodium fluoride ingestion on spermatozoa of the rat. 788 87

Insectivora are of special interest as the most primitive of the eutherian mammals, but essentially nothing is known of their gamete function. In this respect, the Asian musk shrew (Suncus murinus), investigated in the present study, displays many idiosyncrasies. In the epididymis, the giant acrosome undergoes further stabilization, its unusual resilience being especially evident in a "rim" created by a persistent close alignment of the outer acrosomal and overlying plasma membranes. However, until spermatozoa reached a gland on the vas deferens, no post-testicular change was demonstrable in the sperm head surface, the unusual nature of which was indicated by a dorso-ventral differentiation, by an inability to auto-agglutinate or to bind to the homologous zona pellucida, and by an insensitivity to anti-sperm immunoglobulin IgG in fresh serum. At mating, only about 1 x 10(6) spermatozoa are inseminated as far as the anterior vagina with plug formation. Within the small (6 mm) fallopian tube, the isthmus and ampulla are sharply delineated by their contractile activity and epithelial character; there is evidence of some sperm entry into isthmic crypts and a tendency for ipsilateral ovarian control of sperm transport to the tubal ampulla. The cumulus oophorus does not undergo preovulatory mucification and expansion, is characterized by persistent intercellular gap junctions, and is insensitive to hyaluronidase and trypsin. It is unclear how the compact cumulus is penetrated at fertilization. The giant acrosome contains acrosin and an unusually temperature-dependent cumulytic activity; it is intact in motile ampullary spermatozoa but appears to be discharged before reaching the zona pellucida. Since eggs were not penetrated in the presence of ampullary spermatozoa until 4-10 h after ovulation, Suncus spermatozoa spend a long period in the female before they can fertilize. The determinants of sperm function, including capacitation and the acrosome reaction (AR), may depend on a different set of controls in Suncus, perhaps as a legacy of the resilient giant acrosome. This possibility could be examined in other Crociduran and Soricine shrews selected according to acrosome size.
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PMID:Distinctive features of the gametes and reproductive tracts of the Asian musk shrew, Suncus murinus. 819 63


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