Intracellular receptors and agents that induce activation in bovine oocytes

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INTRACELLULAR RECEPTORS AND AGENTS THAT INDUCE ACTIVATION IN BOVINEOOCYTES Kenneth L. White and Caiping Yue Department of Animal, Dairy, and Veterinary Sciences, Biotechnology Center, Utah State University, Logan, UT 84322-48 15 USA ABSTRACT At fertilization, a dramatic change in the intracellular physiology of the oocyte occurs. Intracellular calcium transients have been observed in various species of oocytes including the bovine. These calcium transients have been associated with the early events of oocyte activation. Several reports have evaluated the effects of inositol 1,4,5trisphosphate (IP3) on oocyte activation and its potential role in the events of fertilization. Recent results indicate the existance of both IP3 and ryanodine receptors in bovine oocytes. The events associated with activation and the existance of specific receptors within bovine oocytes will be discussed. OOCYTE ACTIVATION Upon sperm-egg fusion, dramatic physiological changes take place within the fertilized egg. Striking alterations in membrane potential and free intracellular Ca” concentration ([Ca”],) have been observed in various invertebrate and vertebrate species (7, 10, 21). One of the first events observed in the fertilized egg is a propagating Ca*’ wave that begins at the fertilization site and migrates through the cytoplasm to the opposite pole (22, 42). The propagating wave and its corresponding rise in [Ca2’], triggers cortical granule exocytosis and initiates events leading to egg activation, defined as the resumption of second meiosis and second polar body formation (22,30). In the sea urchin, sperm-egg fusion causes a change in membrane potential which is important for an immediate electrical block to polyspermy. A subsequent increase in [Ca”], induces cortical granule exocytosis and development of the fertilization envelope (permanent block to polyspermy; 22). In mammalian eggs, membrane potential changes do not elicit an electrical block to polyspermy (32, 21, 28). However, changes in membrane potential are observed and are manifested as recurring transient hyperpolarization responses (18, 28, 33, 43). These hyperpolarization responses initiated at fertilization are induced by a Ca” activated K conductance and are elicited by periodic transient oscillations [Ca’+], (20). In the fcrtilizcd mammalian egg, periodic transient [Ca”], oscillations occur after sperm-egg fusion and these oscillations have been reported to occur for at least 4 h in the mouse (8) and at least 30 mm in the hamster (30). These periodic transient ]Ca2’], oscillations have also been reported to occur after fertilization in the yig (40) and cattle (11). Maintenance of these recurring oscillations is due to periodic Ca + release from intracellular stores (8, 20). INOSITOL 1,4,5_TRISPHOSPHATE RECEPTORS Data from our laboratory was the first to demonstrate the existence of inositol 1,4,5trisphosphate (IP3) sensitive receptors in bovine oocytes (45, 47). These data have been recently confirmed by Fissore et al. (12) relative to the effects of IP3 and ryanodine agonists and antagonists on induction of intracellular calcium transients in bovine oocytes. These data evaluating the effects of IP3 on intracellular Ca2’ levels in bovine oocytcs compare favorably with the data reported by Sun et al. (40) in which they evaluated intracellular Ca2+ levels after fertilization of porcine oocytes. These data indicate one type of Ca2+ transient that has repetitive peaks similar to those obtained in the mouse and hamster models (4.7 min between peaks vcrscs approximately an 8 min interval in our data). In addition, Sun ct al. (40) reported a second type of Ca” transient that appears similar to those renorted bv Fissore et al. (11) using bovine oocvtcs after fertilization. This second transient was characterized by regular peak: that occurred at intervals of 23.3 min. Experiments of this type are extremely difficult to carryout relative to the long exposure Theriogenology45:91-100, 8

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Theriogenology time required outside of culture conditions. These different Ca” patterns may reflect effects of maintenance conditions during the time course of the measurements or differences in the developmental potential of these oocytes rather than absolute physiological differences in Ca2+ response to fertilization. The results reported by Sun et al. (40) also closely mimic what has been previously described as an IP3 induced Ca2+ transient in all other species studied. It has long been established that increasing the cytosolic [Ca”], in oocytes causes parthenogenetic activation. Various agents and methods used in parthenogenetic activation, including ethanol (5,37), calcium ionophores (7), and microinjection of Ca” (13), elicit a rapid rise in Ca”],. However, these methods have not been shown to induce a series of z transient [Ca ‘Ii oscillations as those observed to occur in fertilized eggs. We have reported the electroporation of IP3 into the cytosol of murine oocytes causes a dramatic rise in [Ca”]. resulting from Ca” release from intracellular stores as well as periodic oscillations in [Ca’L’]ithat persist for a minimum of 20 min in Ca” -free medium (37). In addition, we have also demonstrated that increased [Ca”], levels resulted in higher activation and developmental rates post-fusion after nuclear transplantation (35, 36). We have reported data which indicates repetitive [Ca’+], oscillations, similar to those that have been reported to occur at fertilization, are induced m the bovine oocyte after electroporation of IP3 and result in oocyte activation (45,46).

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Figure 1. Intracellular calcium profiles of bovine oocytes after electroporation of 25 pM IP3. Oocytes were loaded with the calcium indicator Fluo-3. Activation rates of these bovine oocytes were 83% with approximately 35% parthenogenic development to blastocysts.

Ozil (34) reported a study of parthenogenetic activation in rabbit oocytes and described a method designed to mimic prolonged [Ca”], oscillations. Repeated increases in [Ca*+],levels were stimulated by applying a 1.8 kV*cm-1 electric pulse every 4 min for a durauon of 1.5 h. The 22 pulse treatment resulted in a significant increase in rate of development beyond the third cell cycle as compared to single pulse treatment. It was concluded that the process of oocyte activation is not a time limited event and, therefore, repeated increases in [Ca”], may be important in turning on critical cell processes necessary for normal embryonic development. These data also confirm the effect of a specific activation protocol on subsequent development. A similar protocol for activation in conjunction with nuclear transplantation was carried out by Collas and Rob1 (4) in the rabbit. These data reported a significant increase in activation rate and development to the blastocyst stage after multiple pulses as compared to the single pulse. Development was enhanced at both the morula (16% vs 72%) and blastocyst (5% vs 48%) stages following multiple pulses. Activation of recently ovulated (early) oocytes was significantly increased with multiple pulses as compared to a single pulse (85% vs 3%).

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DEVELOPMENTAL CHANGES ASSOCIATE WITH THE IP3 RECEPTORS Oocyte activation results in cell cycle resumption and is associated with a decrease in histone HI kinase activity. The reduction in histone HI kinase activity is an indicator of 3”dcZ/cyclinB kinase activity. Results of experiments evaluating the effects of IP3 on H 1 !&se activity and intracellular calcium release using various ages of in vitro matured bovine oocytes indicate age dependent modifications. Within 5 hours of insemination, HI kinase activity decreased to basal levels in IVF control oocytes (Figure 2A). 45 40 35 30 25 20 15 10 5 0

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kinase activity (Figure 2B). However, infusion of IP3 into 24 and 30 hpm oocytes resulted in an immediate and maintained decrease in Hl kinase activity similar to that observed in IVF oocytes (Figure 2C and 2D). Aged oocytes, 40 hpm, exhibited a much slower (Pc.05) decrease and higher (Pc.05) Hl kinase activity as compared to IVF, 24 hpm and 30 hpm oocytes (Figure 2E). The [Ca”], response of bovine oocytes following IP3 receptor stimulation also Data from our laboratory indicate appears to alter as the bovine oocyte matures. electroporation of 25 pM of IP3 into bovine oocytes after various maturation periods results in distinct differences in the rCaz+l,nrofiles recorded (Fieure 3). These data suerrest a modification in the ability of the oG$e to respond to‘ IF3 which is depender%“on maturation status of the oocyte. These data may further support the hypothesis that differences in bovine oocyte developmental competency may be manifested as alterations in IP3-induced [Ca”], profiles. In addition, these data appear to indicate either IP3 receptors are activated or synthesized as the oocyte matures and subsequent break down in the signal transduction pathway or desensitization of the receptors occurs as the oocyte ages.

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20hpmlIp3 bovine oocytes to IP3 based ““” 24hpm/IF’f on oocyte age. These data represent the average 28hpm/Ip3 response of 5 replicates of 8 oocytes/ maturation time. Oocytes were randomly distributed across all treatment times for each replicate. -

Time (Seconds) CALCIUM-INDUCED CALCIUM RELEASWRYANODINE RECEPTORS The mechanism by which sperm-egg fusion induces hyperpolarizing responses and prolonged [Ca” Ii oscillations remains unclear. One hypothesis is that sperm-egg binding activates receptors affiliated with GTP-binding proteins (G proteins) which in turn activate the phosphoinositide cascade resulting in an increase in the intracellular second messenger IP3 (29). IP3 acts on the endoplasmic reticulum to induce release of stored Ca” by binding to a receptor, thus opening channels for stored Ca*’ to exit into the cytosol. A second hypothesis suggests that IP3 triggers the initial release of Ca2+ from IP3 sensitive stores and this release of stored Ca’+ induces the [Ca2+], oscillations by functioning as a positive regulator for Ca2+induced Ca2+release (CICR) from IP3 insensitive stores (19, 1). Recently, cyclic adenosine diphosphate-ribose (cADPR) has been identified as a potent and powerful factor which induces intracellular calcium release in sea urchin eggs as well as mammalian cells in an IP3-independent mechanism (24,38,9). Microinjection of sperm extract(s) can also induce activation. Stice and Rob1 (39) have reported microinjection of an undefined sperm factor obtained from fractionated rabbit

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Theriogenology sperm induces oocyte activation which exhibits cortical granule exocytosis, pronuclear formation, and cleavages. Unlike most artificial activation methods that are only effective with aged oocytes, injection of this sperm fraction appeared to activate recently ovulated (early) oocytes. Repetitive [Ca”], oscillations that mimic those observed in fertilized oocytes have been elicited in hamster oocytes through microinjection of a sperm factor obtained from hamster and porcine sperm (43). This argues against me model that sperm binding to a receptor-G-protein system induces the repetitive [Ca”], oscillations. Instead, me microinjected sperm factor argues for the model of CICR m propagating [Ca”], oscillations. However, Jaffe (23) has suggested the possibility that the sperm may carry IP3 directly into the oocyte at fertilization and Swann’s data (43) may also support this __ hypothesis. Data from our laboratory indicates a similar response after microinjection of both IP3 and cADPR (47; Figure 4 and 5). These data also indicate IP3-induced oscillations are 4

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Time (Set) Figure 4. Identification of the existence of independent IP3 and ryanodine receptors in bovine oocytes. A, induction of periodic release of [Ca”], after injection of 50-250 nh4 of IP3; B, prior injection of 1 mg/ml of heparin completely inhibits IP3-induced [Ca*‘], release; C, prior injection of ruthenium red (RR, ryanodine antagonist) has no effect on lP3-induced [Ca”], release; D, control injection of vehicle medium (Vh4) has no effect (47). Concentrations are cytosolic after injection.

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inhibited by microinjection of 1 mg/ml concentration of heparin (Figure 4). IP3 appears to be the most potent inducer of [Ca”], release as indicated by its lower effective concentration (50 nM) and the immediate response of oocytes. Injection of IP3 alone induced periodic release of [Ca”], in bovine oocytes as reported in other species. This is in agreement with a previous report using electroporation (49, which strongly argues that the periodic release of [Ca”], was not due to experimental procedure, rather it is the exhibition of oocyte potential to periodically release the [Ca +li when exposed to IP3. It appears the IP3 receptor alone is responsible for the periodic release of [Ca2+], induced by IP3 in bovine oocytes, and CICR is not involved in the formation of a second peak. This conclusion is supported by the observation that the addition of 200 pM thimerosal, which only activates IP3 receptors in bovine oocytes (data not shown), to the culture medium induces [Ca”], oscillations in bovine oocytes preinjected with the ryanodine antagonist procaine at a concentration of 200 PM. It is more likely that the elevation of [Ca2’], may either feed back

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Time (Set) Figure 5. Identification of the existence of ryanodine receptors in bovine oocytes. A, injection of 4-8 uM cADPR induces [Ca”], release; B,Trior injection of 1 mg/ml of heparin has no effect on 100-200 pM ryanodine-induced [Ca +li release; C, induction of [Ca”], after injection of 100-200 pM ryanodine; D, indicates the independence of IP3 and ryanodine receptors, although these receptors may be associated with the same intracellular calcium pool (47).

Theriogenology and activate the IP3 production cascade (17) or it may lower the threshold of IP3 receptors, so that a lower level of IP3 is then able to trigger [Ca”], release from IP3 sensitive stores (2, 31). The appearance of periodic [Ca”], release may rely on the height of first peak which in turn depends on the amount of IP3 injected coupled to the competency of oocytes as indicated by the low proportion of oocytes exhibiting multiple peaks in some reports. Indeed the ability of IP3 to induce multiple peaks of [Ca ‘Ii in bovine oocytes may prove to be an important indication of developmental competence. Data reported by Sun et al. (41) indicate injection of 400 uM of heparin failed to block the formation of a calcium wave during fertilization, although in these experiments, the time between heparin injection and fertilization appeared to be at least 4 hours. Our studies indicate both the introduction of heparin (2 mg/ml) and IP3 (25 PM) into bovine oocytes by electroporation, or prior injection of heparin followed by IP3 resulted in no calcium transients, while lowering the concentration of electroporated heparin to 2 pg/ml, resulted in the same calcium transients as in oocytes without heparin (45, 46). Recent data reported by Fissore et al. (12) appear to contradict those of Sun et al. (41) regarding the effects of heparin on calcium transients in fertilized bovine oocytes. In the experiments by Fissore et al. (12), bovine oocytes were fertilized in vitro and calcium transients monitored. After several calcium transients were identified, oocytes were injected with heparin which resulted in an immediate inhibition of calcium transients. In addition, our data indicate IP3 stimulation of a previously heparin-injected bovine oocyle after 2 hours results in a decreased (0.5 x) calcium response and by 4 hours a normal calcium response depending on the type of heparin used (46). These data appear to indicate the results of Sun et al. (41) may be due to a loss of heparin inhibition. Together all these data indicate the IP3 receptors may not be the sole mechanism that induces calcium waves at fertilization. An alternative receptor may be the cADPR activated ryanodine receptor and further research is needed to evaluate this hypothesis. These data may have important implications for increasing the efficiency of nuclear transplantation in ruminant species. INDEPENDENCE OF IP3 AND RYANODINE RECEPTORS IN BOVINE OOCYTES Heparin at a concentration of 1 mg/ml will completely inhibit the effect of microinjection of W-250 nM IP3, and this inhibition is competitive (16), because injection of 1 uM IP3 overcame the effect of 1 mg/ml heparin (47). However, this inhibitory effect requires prior injection of heparin. A simultaneous injection of higher concentrations of heparin with IP3 failed to inhibit the action of IP3 (47). Ruthenium red (RR) and procaine are known ryanodine receptor antagonists and they, like prior injection of vehicle medium (VM), do not have a significant effect on IP3 receptors as indicated by their inability to affect Il%induced [Ca2’], release (Figure 4C). These results indicate the independence of IP3 and ryanodine receptors. [Ca2+], release upon injection of caffeine is regarded as the hallmark for the existence of ryanodine receptors. In sea urchin oocytes, the response to caffeine is graded in contrast to that in nongerminal cells (3). Experiments with bovine oocytes indicate they respond in a dose dependent manor to microinjection of 1.88-20 mM (47). However, unlike the data reported using sea urchin eggs, the increase in [Ca”], to caffeine was delayed as compared to that for ryanodine. It has been hypothesized that caffeine opens CICR channels, while ryanodine preferentially binds to open channels and locks them in this conformation (25). This hypothesis would suggest caffeine would induce a more rapid response than ryanodine as is the case in sea urchin eggs (14). These conflicting data may indicate the existence of a different type ryanodine receptor in bovine oocytes, which is also supported by the observation that culturing bovine oocytes with 200 uM thimerosal still induced [Ca ‘I, release in oocytes premjected with an inhibitory level of procaine but not in oocytes preinjected with 1 mg/ml heparin. Therefore, thimerosal only activates IP3 receptors in mature bovine oocytes. In contrast, thimerosal activates both IP3 and ryanodine receptors in sea urchin eggs (15,44).

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Theriogenology Freshly prepared cADPR (4-8 pM) also induced a significant [2Caz+], release (Figure 5A) while frozen-thawed cADPR solution was unable to induce [Ca +li release. Injection of 1% VM did not significantly change the [Ca”], level (Figure 4D), which also argues against the possibility that contaminating Ca” in VM or that the injection itself induced an artifact. However, the requirement for such a high concentration of cADPR and the observation that frozen-thawed cADPR solution failed to induce [Ca”], release in bovine oocytes, while the same frozen-thawed cADPR solution was still fully active on sea urchin egg homogenate (personal communication, H.C. Lee) leads to the following possibilities. First, the ryanodine receptor in bovine oocytes may be different from that in sea urchin eggs and has a decreased affinity for cADPR. Freeze-thawing may decrease the bioactivity of cADPR enough to prevent the activation of the ryanodine receptor in bovine oocytes. Second, it has been reported that in skeletal muscle cADPR binds to ryanodine receptors but does not elicit the release of [Ca’+], and that it may not be an effective endogenous modulator at the concentration of 2 pM (27). The same phenomenon may be applicable in bovine oocytes. Ryanodine antagonists such as ruthenium red and procaine were all able to competitively inhibit the effect of ryanodine agonists. Ryanodine antagonists had no effect on subsequent IP3-induced [Ca”], release (Figure 4C). Injection of heparin or VM did not significantly affect the [Ca”], release induced by ryanodine agonists (Figure 5B), which indicates the independent relationship between IP3 and ryanodine receptors. DESENSITIZATION OF II’3 AND RYANODINE RECEPTORS As reported in sea urchin eggs (6, 15, 26), desensitization is a major characteristic of IP3 and ryanodine receptors and has been used to distinguish these two receptor types. In bovine oocytes, a 15 minute refractory period was observed after the initiation of [Ca”], release induced by 200 nM IP3 or a 10 minute refractory period for 200 pM ryanodine and lo-20 n&l caffeine (47). The ability of caffeine and ryanodine to desensitized ryanodine receptors to each other reinforces the concept that they use the same receptor to mobilize [Ca ‘Ii. The independent relationship between IP3 and ryanodine receptors were further evaluated by injecting IP3 (or ryanodine) immediately after the initiation of [Ca2+], release induced by ryanodine (or IP3; Figure 5D). Since during this period the IP3 receptor is still desensitized to IP3, the release of [Ca2’], induced by ryanodine must be the result of activating ryanodine receptors which are not desensitized by the prior injection of IP3. The same is true for the reverse. The low amplitude of [Ca2’], peak induced by the second injection (Fig. 5F, G) may be due to either the possible overlapping of two stores as reported in sea urchin eggs (6) or to the down regulation of receptor sensitivity by [Ca’+], level (2). CONCLUSIONS The existence of both IP3 and ryanodine receptors in mature bovine oocytcs has been established. These receptors are independent and coexist in mature bovine oocytes; ryanodine receptors in bovine oocytes may be different from those found in sea urchin eggs. The identification of ryanodine receptors in bovine oocytes will provide impetus to screen other farm animals for its presence. It appears clear, IP3 plays a role in early events associated with activation in bovine oocytes. Further research is required to elucidate the effect and potential relationship of these dual receptors in the events associated with bovine fertilization. REFERENCES 1. 2.

Berridge MJ. Inositol triphosphate-induced membrane potential oscillations in Xenopus oocytes. J Physiol 1988;403:589-599. Berridge MJ. Inositol trisphosphate and calcium signalling. Nature 1993;361:315325.

Theriogenology

3. 4. 5. 6. I. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26.

Buck WR, Hoffmann EE, Rakow TL, Shen SS. Synergistic calcium release in the sea urchin egg by ryanodine and cyclic ADP ribose.bev Biol 1994;163: l-10. Collas P, Rob1 JM. Factors affecting efficiency of nuclear transplantation in the rabbit. Biol Reprod 1990; 43877-884. Colonna R, Tatone C, Malgaroli A, Eusebi F, Mangia F. Effects of protein kinase C stimulation and free Ca’+ rise in mammalian egg __ activation. Gamete Res 1989;24:171-183. Clapper DL, Lee HC. Inositol trisphosphate induces calcium release from nonmitochondrial stores in sea urchin egg homogenates. J Biol Chem 1985;260:13947-13954. Cuthbertson KSR, Whittingham DG, Cobbold PH. Free Ca” increases in exponential phases during mouse oocyte activation. Nature 198 1;294: 754-7.57 Cuthbertson KSR, Cobbold PH. Phorbol ester and sperm activate mouse oocytes by inducing sustained oscillations in cell Ca” Nature 1985;316:541-542. Dargie PJ, Agre MC, Lee HC. Comparison of Ca*’ mobilizing activities of cyclic ADP-ribose and inositol triphosphate. Cell Regul 1990;1:279-290. Epel D. The physiology and chemistry of calcium during the fertilization of eggs, In: Calcium and Cell Function. Academic Press, Inc, New York, 1982;Vol.I1:355-383. Fissore RA, Dobrinsky JR, Balise JJ, Duby RT, Robl. JM. Patterns of intracellular Ca*’ concentrations in fertilized bovine eggs, Biol Reprod 1992;47:960-969. Fissore RA, Pinto-Correia C, Rob1 JM. Inositol trisphosphate-induced calcium release in the generation of calcium oscillations in bovine eggs. Biol Reprod 1995;53:766774. Fulton BP, Whittingham DG. Activation of mammalian oocytes by intracellular injection of calcium. Nature 1978;273:149-151. Galione A, Lee HC, Busa W B. Ca*’ -induced CaZ’ release in sea urchin egg homogenates: modulation by cyclic ADP-Ribose. Science 1991; 253:1143-l 146. Galione A, McDougall A, Busa W B, Willmott N, Gillot I, Whitaker M. Redundant mechanisms of calcium-induced calcium release underlying calcium waves during fertilization of sea urchin eggs. Science 1993;261:348-352. Ghosh T K, Eis PS, Mullaney J M, Ebert C L, Gill DL. Competitive, reversible, and potent antagonism of inositol 1,4,5-trisphosphate-activated calcium release by heparin. J Biol Chem 1988;263: 11075-l 1079. Harootunian AT, Kao JPY, Paranjape S, Tsien RY. Generation of calcium oscillations in tibroblasts by positive feedback between calcium and IP3. Science 1991:251:75-78. Igusa Y, Miyazaki S, Yamashita N. Periodic hyperpolarizing responses in hamster and mouse eges fertilized with mouse sperm. J Phvsiol 1983:340:633-647. Igusa Y, Miy&aki S. Effects of altered extracellular and intracellular calcium concentration on hyperpolarization responses of the hamster egg. J Physiol 1983;340:611-632. Igusa Y, Miyazaki S. Periodic increase of cytoplasmic calcium in fertilized hamster eggs measured with calcium-sensitive electrodes, J Physiol 1986;377: 193-205. Jaffe LF. Sources of calcium in egg activation: A review and hypothesis. Dev Biol 1983;99:265-276, Jaffe LF. The role of calcium explosions, waves and pulses in activating eggs, In: Metz CB, Monroy A (eds) Biology of Fertilization. Academic Press, New York, 1985: 127-165. Jaffe LF. The roles of intermembrane calcium in polarizing and activating eggs. In: Dale B (ed). Mechanism of Fertilization. Springer-Verlag, New York, 1990;389417. Koshiyama H, Lee HC, Tashjian Jr AH. Novel mechanism of intracellular calcium release in nituitarv cells, J Biol Chem 1991:266:16985-16988. Lai F A, Meissner G. The muscle ryanodine receptor and its intrinsic Ca2+ channel activity. J Bioenerg Biomemb 1989;21:227-246, Lee H C, Aarhus R, Walseth TF. Calcium mobilization by dual receptors during fertilization of sea urchin eggs. Science 1993;261:352-355.

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Theriogenology

27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47.

MCszaros LG, Bak J, Chu A. Cyclic ADP-ribose as an endogenous regulator of the non-skeletal type ryanodine receptor Ca2+ channel. Nature 1993;364:76 79. McCulloh DH, Rexroad Jr CE, Levitan H. Insemination of rabbit eggs is associated with slow depolarization and repetitive diphasic membrane potentials. Dev Biol 1983;95:372-377. Miyazaki S. Inositol 1,4,5-triphosphate-induced calcium release guanine nucleotide binding protein-mediated periodic calcium rises in golden hamster eggs. J Cell Biol 1988;106:345 354. Miyazaki S, Hashimoto N, Yoshimoto Y, Kishimoto T, Igusa Y, Hiramoto Y. Temporal and spatial dynamics of the periodic increase in intracellular free calcium at fertilization of golden hamster eggs. Dev Biol 1986;118:259-267. Miyazaki S, Yuzaki M, Nakada K, Shirakawa H, Nakanishi S, Nakade S, Mikoshiba K. Block of Ca2+wave and Ca” oscillation by antibody to the inositol 1,4,5_trisphosphate receptor in fertilized hamster eggs. Science 1992;257:251-255. Miyazaki S, Igusa Y. Ca-mediated activation of a K current at fertilization of golden hamster eggs. Proc Nat1 Acad Sci USA 1982;79:931-935. Miyazaki S, Igusa Y. Fertilization potential in golden hamster eggs consists of recurring hyperpolarizations. Nature 198 1;290:702-704. Ozil JP. The parthenogenetic development of rabbit oocytes after repetitive pulsatile electrical stimulation. Development 1990;109:117-127. Rickords LF, White KL. Electrofusion induced intracellular Ca” flux and its effect on murine oocyte activation. Mol Reprod Dev 1992a;31:152-159. Rickords LF. White KL. Effect of electrofusion nulse in either electrolvte or nonelectrolyte fusion medium on subsequent murine embryonic development. Mol Reprod Dev 1992b;32:259-264. Rickords LF, White KL. Electroporation of inositol 1,4,5triphosphate induces repetitive calcium oscillations in murine oocytes. J Exp Zoo1 1993;265:178-184. Rusinko N, Lee HC. Widespread occurrence in animal tissues of an enzyme catalyzing the conversion of NAD+ into a cyclic metabolite with intracellular Ca*’ mobilizine activitv. J Biol Chem 1989:264:11725-l 173 1. Stice SL, Rob1 Jd. Activation of mammalian oocytes by a factor obtained from rabbit sperm. Biol Reprod 1990;25:272-280. Sun FZ, Hoyland 3, Huang H, Mason W, Moor RM. A comparison of intracellular changes in porcine eggs after fertilization and electroactivatioa Development 1992;115: 947-956. Sun F Z, Bradshaw JP, Galli C, Moor RM. Changes in intracellular calcium concentration in bovine oocytes following penetration by spermatozoa. J Reprod Fertil 1994;101:713-719, Swann K, Whitaker MJ. The parts played by inositol triphosphate and calcium in the propagation of the fertilization wave in sea urchin eggs. J Cell Biol 1986;103:2333-2342. Swarm K. A cytosolic sperm factor stimulates repetitive calcium increases and mimics fertilization in hamster eggs. Development 199O;llO: 1295-1302. Tanaka Y, Tashjian AJ. Thimero&i potentiates Ca2+ release mediated by both the inositol 1,4,5_trisphosphate and the ryanodine receptors in sea urchin eggs. J Biol Chem 1994;269:11247-11253. White KL, Bunch TD, Reed WA, Wang S, Yue C. Bovine oocyte activation is mediated by IP3-sensitive intracellular calcium pools. Annual Meetings of The Society For The Study of Reproduction, Fort Collins, CO, 1993;346. White KL, Bunch TD, Reed WA, Yue C. Bovine oocyte activation can be mediated bv IP3-sensitive intracellular calcium nools. 1995;Submitted. Y%e C, White KL, Reed WA, Bunch TD. The existence of inositol 1,4,5trisphosphate and ryanodine receptors in mature bovine oocytes. Development 1995;121:2645-2654.