Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper presents morphological data on mouse oocyte maturation and fertilization, reviews evidence supporting the existence of a sperm receptor, and suggests future directions for this line of research. We used scanning electron microscopy to examine oocytes under a variety of conditions. The surfaces of mature mouse oocytes are seen to be similar whether maturation occurs in vivo or in vitro. Capacitated sperm (both acrosome-intact and acrosome-reacted) are observed to interact with the microvilli of the oocyte surface. Little is known about oocyte surface proteins that mediate fertilization in mammals. Data of ours and others show that enzyme treatment of live unfertilized eggs interferes with sperm binding. Enzyme treatment (trypsin, chymotrypsin treatment, or pronase) reduces the number of bound sperm, suggesting removal of a surface protein involved in fertilization. Trypsin treatment also causes some lengthening of surface microvilli in a belt surrounding the metaphase II region. After metabolic labeling, proteins of zona-free unfertilized eggs can be identified by SDS-PAGE and autoradiography. Comparison of 1-D gels from untreated and enzyme-treated eggs show the nearly complete disappearance of proteins of 263, 170, 137, 97, and 87 kD after digestion; an increase in a 66 kD protein after trypsin or chymotrypsin; and a major new band of 20 kD after chymotrypsin treatment. Fertilized eggs show the loss of a 255-265 kD band among other changes. Proteins of 97 kD and 87 kD were seen previously by surface labeling (Johnson and Calarco, 1980b), and our 97 kD and 66 kD bands are similar in molecular weight to those identified by Boldt et al. (1989). Taken together, these data identify a few candidate proteins for the role of sperm receptor on the egg surface. Future work should focus on identification of the surface protein(s) which functions physiologically in fertilization by developing fertilization-blocking antibodies. Relatedness to other mammalian sperm receptors and identification of the genes involved would provide valuable information to our understanding of fertilization and to the problems of infertility and contraception.
 ...
PMID:Fertilization of the mouse oocyte. 186 39

Three different micromanipulation procedures were used to assist human fertilization in cases of severe male factor infertility. Zona drilling was performed either with acid Tyrode's solution, mechanically following zona softening with chymotrypsin, or by partial zona dissection. The fertilization rate was lowest in the zona drilling/acid Tyrode's group (7/40; 17.5%), although no differences between groups (zona drilling/chymotrypsin: 21/84, 25%; partial zona dissection: 31/143, 21.7%) were significant. The fertilization rate was significantly increased relative to untreated eggs from the same patients only in the partial zona dissection group (31/143, 21.7% versus 4/102, 3.9%). Oocyte damage occurred at a high rate as a result of zona drilling with acid Tyrode's solution (13/41, 37%). Embryonic development was compromised after zona drilling with chymotrypsin: only 7/12 (58.3%) of the fertilized oocytes cleaved, and the morphology of many of the cleaved embryos was abnormal. Although only 61% (16/26) of the diploid embryos resulting from partial zona dissection cleaved, the embryonic morphology of these embryos was comparable with controls. No pregnancies resulted from the transfer of manipulated embryos. We conclude that although zona manipulation increases the fertilization rate, losses due to oocyte trauma, low rates of diploid fertilization, low rates of cleavage, and a high frequency of abnormal cleavage reduce the number of embryos available for transfer.
 ...
PMID:Clinical evaluation of three approaches to micromanipulation-assisted fertilization. 220 88

Failure of the human ejaculate to liquefy can be the cause of infertility. We report one such case in which liquefaction of the coagulated ejaculate was effected by alpha-chymotrypsin in-vitro and led to pregnancy after homologous in semination.
 ...
PMID:[Pregnancy after treatment of ejaculate with alpha-chymotripsine because of failure to liquefy]. 655 15

Fertilization of a mouse egg results in modification of the cytoplasmatic membrane (oolemma) which makes fusion with additional sperm impossible. CD9 is a transmembrane protein reported to be responsible for gamete fusion. Since the molecular mechanism of zygote membrane modification after fertilization remains unknown, we were interested to check whether lack of CD9 is the reason for non-penetrability of zona-free zygotes. We wanted also to determine the effect of different methods of zona pellucida removal on the presence of CD9 on the surface of unfertilized eggs and their ability to be fertilized afterwards. We demonstrated that CD9 is present on the surface of both zygotes and parthenogenotes. We showed also that the treatment of eggs with pronase completely removes CD9 from the membrane of eggs making them infertile. Eggs treated with chymotrypsin and acid Tyrode still posses CD9 on their surface and remain fertile. The results of our experiments indicate that modification of the zygote oolemma does not involve a lack of CD9. We cannot exclude however, that the amount of CD9 decreases after fertilization. In addition, our studies indicate that the previously reported infertility of eggs treated with different proteases may result from the decrease or removal of CD9 and probably other proteins responsible for gamete fusion from the surface of eggs.
 ...
PMID:Distinct mechanisms underlie sperm-induced and protease-induced oolemma block to sperm penetration. 1265 53

In vitro fertilization-embryo transfer seems to be an effective treatment for unexplained infertility. Some IVF centers always perform intracytoplasmic sperm injection in these circumstances being concerned that fertilization failure may occur by conventional oocyte insemination. However, other IVF centers perform intracytoplasmic sperm injection on half of the oocytes and do conventional insemination on the other half. However, if the group with conventional oocyte insemination had a good fertilization rate, in the future intracytoplasmic sperm injection would not be performed. Other IVF centers would inseminate all the oocytes with conventional insemination and not consider intracytoplasmic sperm injection in the future unless there were poor fertilization rates. The aforementioned studies suggest that prior to considering conventional insemination that as a minimum the simple inexpensive hypo-osmotic swelling test be performed and strong consideration also be given to the sperm stress test and SCSA. Similarly, even though IUI is less risky and costly than IVF-ET, there still is a moderate expense and risk involved, especially when superovulation is used. Thus, consideration for performing these tests should also be given even prior to IUI. This is especially important for subnormal HOST scores where pretreatment of the sperm with the protein digestive enzyme chymotrypsin when preparing the sperm has been demonstrated to markedly improve pregnancy rates.
 ...
PMID:Sperm may be associated with subfertility independent of oocyte fertilization. 1586 25

Animal venoms are small natural mixtures highly enriched in bioactive components. They are known to target at least two important pharmacological classes of cell surface receptors: ion channels and G protein coupled receptors. Since sperm cells express a wide variety of ion channels and membrane receptors, required for the control of cell motility and acrosome reaction, two functions that are defective in infertility issues, animal venoms should contain interesting compounds capable of modulating these two essential physiological functions. Herein, we screened for bioactive compounds from the venom of the Egyptian black snake Walterinnesia aegyptia (Wa) that possess the property to activate sperm motility in vitro from male mice OF1. Using RP-HPLC and cation exchange chromatography, we identified a new toxin of 6389.89 Da (termed walterospermin) that activates sperm motility. Walterospermin was de novo sequenced using a combination of matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/TOF MS/MS) and liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF MS/MS) following reduction, alkylation, and enzymatic proteolytic digestion with trypsin, chymotrypsin or V8 protease. The peptide is 57 amino acid residues long and contains three disulfide bridges and was found to be identical to the previously cloned Wa Kunitz-type protease inhibitor II (Wa Kln-II) sequence. Moreover, it has strong homology with several other hitherto cloned Elapidae and Viperidae snake toxins suggesting that it belongs to a family of compounds able to regulate sperm function. The synthetic peptide shows promising activation of sperm motility from a variety of species, including humans. Its fluorescently-labelled analog predominantly marks the flagellum, a localization in agreement with a receptor that controls motility function.
 ...
PMID:Identification, Characterization and Synthesis of Walterospermin, a Sperm Motility Activator from the Egyptian Black Snake Walterinnesia aegyptia Venom. 3309 70