Regulation of membrane stability and the acrosome reaction in mammalian sperm

Membrane destabilization is an essential step in the process of membrane fusion. In many cell types, exocytotic fusion may occur sporadically at microscopically localized sites on the surface of the cell, making it difficult to study the chemical and physical features of the membrane (or membranes) that promote fusion. In the sperm cell, exocytosis occurs synchronously at a distinct region on the sperm head. This localization of function makes the sperm cell a useful model to investigate the structural features of the bilayers that control membrane fusion. During sperm maturation, the anterior head membranes undergo a well‐defined series of chemical, physical, and functional changes that are necessary to produce a fertile gamete. These changes include the addition of highly unsaturated phosphatidylcholine, a decrease in general membrane stability, and an increase in the ability to respond to physiological and pharmacological inducers of exocytosis. Concomitant addition of cholesterol and an actively maintained asymmetric transmembrane phospholipid distribution modulate these effects to stabilize the membrane of the mature sperm for storage. The environment of the female tract provides conditions that promote efflux of cholesterol from the sperm plasma membrane as well as the loss of membrane asymmetry. The cholesterol‐poor, lipid‐symmetric plasma membrane has a destabilized inner leaflet that facilitates membrane fusion upon binding of the sperm to the appropriate egg coat receptors. We summarize these features in a mechanistic model in which the sperm membrane contains destabilizing components to confer fusogenic potential as well as stabilizing components organized to maximize membrane integrity. This combination prevents premature fusion in the male tract. After deposition in the female tract and removal of the stabilizing components, followed by reorganization of the fusogenic components, the membrane becomes poised to fuse upon receipt of the final biological stimulus.—Nolan, J. P., Hammerstedt, R. H. Regulation of membrane stability and the acrosome reaction in mammalian sperm. FASEB J. 11, 670–682 (1997)

[1]  M. B. Kelly,et al.  Contribution of hydrogen bonding to lipid-lipid interactions in membranes and the role of lipid order: effects of cholesterol, increased phospholipid unsaturation, and ethanol. , 1993, Biochemistry.

[2]  J. S. Agustin,et al.  The structure of caltrin, the calcium-transport inhibitor of bovine seminal plasma. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[3]  S. Meizel,et al.  Studies of phospholipase A2 related to the hamster sperm acrosome reaction. , 1982, The Journal of experimental zoology.

[4]  T. E. Thompson,et al.  Cholesterol-induced fluid-phase immiscibility in membranes. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[5]  T. Gadella,et al.  Visualization and quantification of glycolipid polarity dynamics in the plasma membrane of the mammalian spermatozoon. , 1994, Journal of cell science.

[6]  S. Meizel,et al.  Phosphatidylinositol 4,5-bisphosphate hydrolysis in human sperm stimulated with follicular fluid or progesterone is dependent upon Ca2+ influx. , 1989, The Biochemical journal.

[7]  D. Hoekstra,et al.  Evidence for the existence of lipid-diffusion barriers in the equatorial segment of human spermatozoa. , 1994, Biochemical Journal.

[8]  P. Blackmore,et al.  Cell surface-binding sites for progesterone mediate calcium uptake in human sperm. , 1991, The Journal of biological chemistry.

[9]  P. Manjunath,et al.  Major proteins of bovine seminal vesicles bind to spermatozoa. , 1994, Biology of reproduction.

[10]  P. Wassarman,et al.  O-linked oligosaccharides of mouse egg ZP3 account for its sperm receptor activity , 1985, Cell.

[11]  P. Wassarman,et al.  Profile of a mammalian sperm receptor. , 1990, Development.

[12]  R. Demel,et al.  The properties of polyunsaturated lecithins in monolayers and liposomes and the interactions of these lecithins with cholesterol , 1972 .

[13]  S. Rubinstein,et al.  Epidermal growth factor induces acrosomal exocytosis in bovine sperm , 1994, FEBS letters.

[14]  C. Ho,et al.  Hydration and order in lipid bilayers. , 1995, Biochemistry.

[15]  T. Gadella,et al.  Glycolipid migration from the apical to the equatorial subdomains of the sperm head plasma membrane precedes the acrosome reaction. Evidence for a primary capacitation event in boar spermatozoa. , 1995, Journal of cell science.

[16]  C. R. Austin,et al.  The ‘Capacitation’ of the Mammalian Sperm , 1952, Nature.

[17]  R. Hammerstedt,et al.  Evaluation of plasma membrane stability by detergent-induced rupture of osmotically swollen sperm. , 1992, Journal of biochemical and biophysical methods.

[18]  D. Babcock,et al.  Activation of voltage-dependent calcium channels of mammalian sperm is required for zona pellucida-induced acrosomal exocytosis. , 1992, Developmental biology.

[19]  R. Hammerstedt,et al.  Yield, characteristics, motility and cAMP content of sperm isolated from seven regions of ram epididymis. , 1982, Biology of reproduction.

[20]  A. D. Fleming,et al.  Effects of various lipids on the acrosome reaction and fertilizing capacity of guinea pig spermatozoa with special reference to the possible involvement of lysophospholipids in the acrosome reaction , 1981 .

[21]  B. T. Storey,et al.  Activation of a Gi protein in mouse sperm membranes by solubilized proteins of the zona pellucida, the egg's extracellular matrix. , 1992, The Journal of biological chemistry.

[22]  M. Straume,et al.  Equilibrium and dynamic structure of large, unilamellar, unsaturated acyl chain phosphatidylcholine vesicles. Higher order analysis of 1,6-diphenyl-1,3,5-hexatriene and 1-[4-(trimethylammonio)phenyl]- 6-phenyl-1,3,5-hexatriene anisotropy decay. , 1987, Biochemistry.

[23]  P. Devaux,et al.  Static and dynamic lipid asymmetry in cell membranes. , 1991, Biochemistry.

[24]  D. E. Wolf,et al.  Diffusion and regionalization in membranes of maturing ram spermatozoa , 1984, The Journal of cell biology.

[25]  Steven S. Vogel,et al.  Lysolipids reversibly inhibit Ca2+‐, GTP‐ and pH‐dependent fusion of biological membranes , 1993, FEBS letters.

[26]  J. Calvete,et al.  Quantitation of boar spermadhesins in accessory sex gland fluids and on the surface of epididymal, ejaculated and capacitated spermatozoa. , 1994, Biochimica et biophysica acta.

[27]  R. Hammerstedt,et al.  Changes in sperm surfaces associated with epididymal transit. , 2019, Journal of reproduction and fertility. Supplement.

[28]  D. Babcock,et al.  An adhesion-associated agonist from the zona pellucida activates G protein-promoted elevations of internal Ca2+ and pH that mediate mammalian sperm acrosomal exocytosis. , 1989, Developmental biology.

[29]  G. Kopf,et al.  Capacitation of mouse spermatozoa. I. Correlation between the capacitation state and protein tyrosine phosphorylation. , 1995, Development.

[30]  H. Florman.  Sequential focal and global elevations of sperm intracellular Ca2+ are initiated by the zona pellucida during acrosomal exocytosis. , 1994, Developmental biology.

[31]  E. Dratz,et al.  CHAPTER 16 – THE ROLE OF DOCOSAHEXAENOIC ACID (22:6ω3) IN BIOLOGICAL MEMBRANES: EXAMPLES FROM PHOTORECEPTORS AND MODEL MEMBRANE BILAYERS1 , 1986 .

[32]  J. Bentz.  Intermediates and kinetics of membrane fusion. , 1992, Biophysical journal.

[33]  M. Nikolopoulou,et al.  Changes in the lipid content of boar sperm plasma membranes during epididymal maturation. , 1985, Biochimica et biophysica acta.

[34]  P. Cullis,et al.  Modulation of membrane fusion by asymmetric transbilayer distributions of amino lipids. , 1994, Biochemistry.

[35]  R. Williams,et al.  Determination of the capacity of ram epididymal and ejaculated sperm to undergo the acrosome reaction and penetrate ova. , 1991, Biology of reproduction.

[36]  D. E. Wolf,et al.  Lateral regionalization and diffusion of a maturation-dependent antigen in the ram sperm plasma membrane , 1986, The Journal of cell biology.

[37]  A. Baracca,et al.  Dynamics of biological membranes. , 1988, Annali dell'Istituto superiore di sanita.

[38]  A. Herrmann,et al.  Protein-dependent translocation of aminophospholipids and asymmetric transbilayer distribution of phospholipids in the plasma membrane of ram sperm cells. , 1994, Biochemistry.

[39]  S. Singer,et al.  The fluid mosaic model of the structure of cell membranes. , 1972, Science.

[40]  D. E. Wolf,et al.  The Sperm Plasma Membrane A Little More Than Mosaic, a Little Less Than Fluid , 1990 .

[41]  J. Nolan,et al.  Effect of dilauroylphosphatidylcholine liposomes on motility, induction of the acrosome reaction, and subsequent egg penetration of ram epididymal sperm. , 1991, Biology of reproduction.

[42]  Steven S. Vogel,et al.  Lysophosphatidylcholine reversibly arrests exocytosis and viral fusion at a stage between triggering and membrane merger. , 1993, The Journal of biological chemistry.

[43]  D. Leckband,et al.  Role of calcium in the adhesion and fusion of bilayers. , 1993, Biochemistry.

[44]  J. Nolan,et al.  Artificial induction of exocytosis in bull sperm. , 1992, Archives of biochemistry and biophysics.

[45]  P. Devaux,et al.  ATP-dependent asymmetric distribution of spin-labeled phospholipids in the erythrocyte membrane: relation to shape changes. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[46]  J. Israelachvili,et al.  Role of hydrophobic forces in bilayer adhesion and fusion. , 1992, Biochemistry.

[47]  R. Foote,et al.  Lipids of plasma membrane and outer acrosomal membrane from bovine spermatozoa. , 1987, Biology of reproduction.

[48]  G S Kopf,et al.  Capacitation of mouse spermatozoa. II. Protein tyrosine phosphorylation and capacitation are regulated by a cAMP-dependent pathway. , 1995, Development.

[49]  L L van Deenen,et al.  The properties of polyunsaturated lecithins in monolayers and liposomes and the interactions of these lecithins with cholesterol. , 1972, Biochimica et biophysica acta.

[50]  D. Veeramachaneni,et al.  The epididymis and sperm maturation: a perspective. , 1993, Reproduction, fertility, and development.

[51]  R. Foote,et al.  Bovine oviductal fluid components and their potential role in sperm cholesterol efflux , 1990, Molecular reproduction and development.

[52]  M. Courot,et al.  Electron microscopic study of the in vivo zona pellucida binding ability of epididymal ram spermatozoa , 1986 .

[53]  C. Ho,et al.  Gramicidin conformational studies with mixed-chain unsaturated phospholipid bilayer systems. , 1992, Biochemistry.

[54]  R. Schlegel,et al.  Effect of transbilayer phospholipid distribution on erythrocyte fusion , 1989, Bioscience reports.

[55]  B. T. Storey,et al.  Selective activation of Gi1 and Gi2 in mouse sperm by the zona pellucida, the egg's extracellular matrix. , 1994, The Journal of biological chemistry.

[56]  R. Burgoyne,et al.  Regulated exocytosis. , 1993, The Biochemical journal.

[57]  G. Fairbanks,et al.  Post-testicular developmental changes in the ram sperm cell surface and their relationship to luminal fluid proteins of the reproductive tract. , 1980, Biology of reproduction.

[58]  J. Courtens,et al.  Acquisition of zona binding by ram spermatozoa during epididymal passage, as revealed by interaction with rat oocytes , 1982 .

[59]  P. Blackmore,et al.  Progesterone and 17 alpha-hydroxyprogesterone. Novel stimulators of calcium influx in human sperm. , 1990, The Journal of biological chemistry.

[60]  P. Bütikofer,et al.  Transbilayer mobility and distribution of red cell phospholipids during storage. , 1993, The Journal of clinical investigation.

[61]  R. Schlegel,et al.  Phospholipid asymmetry in human erythrocyte ghosts , 1985, Journal of cellular physiology.

[62]  S. Grimaldi,et al.  Effect of erythrocyte transbilayer phospholipid distribution on fusion with vesicular stomatitis virus. , 1990, Biochemistry.

[63]  Michael Edidin,et al.  Patches and fences: probing for plasma membrane domains , 1993, Journal of Cell Science.

[64]  G. Colas,et al.  Observations on the motility and fertilizing ability of ram epididymal spermatozoa , 1977 .

[65]  D. Siegel,et al.  Energetics of intermediates in membrane fusion: comparison of stalk and inverted micellar intermediate mechanisms. , 1993, Biophysical journal.

[66]  C. W. Browning,et al.  Use of merocyanine (MC540) in quantifying lipid domains and packing in phospholipid vesicles and tumor cells. , 1993, Biochimica et biophysica acta.

[67]  H. Florman,et al.  Caltrin, the calcium transport regulatory peptide of spermatozoa, modulates acrosomal exocytosis in response to the egg's zona pellucida. , 1993, The Journal of biological chemistry.

[68]  R. Koynova,et al.  The effect of nonideal lateral mixing on the transmembrane lipid asymmetry. , 1985, Biochimica et biophysica acta.

[69]  M. Eisenbach,et al.  Potential assays for sperm capacitation in mammals. , 1994, The American journal of physiology.

[70]  T. Stegmann,et al.  Inhibition of Influenza-induced Membrane Fusion by Lysophosphatidylcholine (*) , 1995, The Journal of Biological Chemistry.

[71]  J. Langlais,et al.  A molecular membrane model of sperm capacitation and the acrosome reaction of mammalian spermatozoa , 1985 .

[72]  G. Kopf,et al.  A guanine nucleotide‐binding regulatory protein in human sperm mediates acrosomal exocytosis induced by the human zona pellucida , 1992, Molecular reproduction and development.

[73]  R. Hammerstedt,et al.  Development changes occurring in the lipids of ram epididymal spermatozoa plasma membrane. , 1985, Biology of reproduction.

[74]  B. Roelofsen,et al.  Flip-flop rates of individual molecular species of phosphatidylcholine in the human red cell membrane. , 1986, Biochimica et biophysica acta.

[75]  G. Fairbanks,et al.  Studies on mechanisms of surface modifications in ram spermatozoa during the final stages of differentiation. , 1982, Biology of reproduction.

[76]  P. Morales,et al.  Studies of lysophospholipids related to the hamster sperm acrosome reaction in vitro. , 1993, The Journal of experimental zoology.

[77]  R. Posner,et al.  Flow cytometric analysis of transmembrane phospholipid movement in bull sperm. , 1995, Biochemistry.

[78]  G. Colas,et al.  Epididymal sperm maturation in the ram : motility, fertilizing ability and embryonic survival after uterine artificial insemination in the ewe , 1979 .

[79]  J. Baenziger,et al.  Molecular motions and dynamics of a diunsaturated acyl chain in a lipid bilayer: implications for the role of polyunsaturation in biological membranes. , 1992, Biochemistry.

[80]  P. Cullis,et al.  Lipid Polymorphism, Lipid Asymmetry and Membrane Fusion , 1988 .

[81]  L. Leyton,et al.  95 kd sperm proteins bind ZP3 and serve as tyrosine kinase substrates in response to zona binding , 1989, Cell.