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New insights into the regulation of cholesterol efflux from the sperm membrane.

Leahy T, Gadella BM - Asian J. Androl. (2015 Jul-Aug)

Bottom Line: How does a hydrophobic cholesterol molecule inserted in the sperm plasma membrane enter the energetically unfavorable aqueous surroundings?The overall aim is to better understand cholesterol redistribution in the sperm plasma membrane, its relation to the possible activation of a cholesterol transporter and the role of cholesterol acceptors.Armed with such knowledge, sperm handling techniques can be adapted to better prepare spermatozoa for in vitro and in vivo fertilization.

View Article: PubMed Central - PubMed

Affiliation: Department of Farm Animal Health and of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 2, 3584 CM Utrecht, The Netherlands.

ABSTRACT
Cholesterol is an essential component of the mammalian plasma membrane because it promotes membrane stability without comprising membrane fluidity. Given this important cellular role, cholesterol levels are tightly controlled at multiple levels. It has been clearly shown that cholesterol redistribution and depletion from the sperm membrane is a key part of the spermatozoon's preparation for fertilization. Some factors that regulate these events are described (e.g., bicarbonate, calcium) but the mechanisms underlying cholesterol export are poorly understood. How does a hydrophobic cholesterol molecule inserted in the sperm plasma membrane enter the energetically unfavorable aqueous surroundings? This review will provide an overview of knowledge in this area and highlight our gaps in understanding. The overall aim is to better understand cholesterol redistribution in the sperm plasma membrane, its relation to the possible activation of a cholesterol transporter and the role of cholesterol acceptors. Armed with such knowledge, sperm handling techniques can be adapted to better prepare spermatozoa for in vitro and in vivo fertilization.

No MeSH data available.


Orientation of cholesterol and desmosterol in a lipid bilayer. (a) The lipid-disordered membrane phase contains low levels of cholesterol. The membrane is fluid and has high lateral diffusion characteristics. At 4°C this membrane fraction is solubilized by detergents (detergent soluble membrane fraction). Most transmembrane proteins fit into this membrane fraction because of their α-helix transmembrane domain(s). (b) The lipid ordered phase of a membrane is still fluid but is stabilized by high levels of cholesterol. At 4°C this membrane is not solubilized by detergents and proteins and lipids can be purified in a so-called detergent-resistant membrane fraction. The exoplasmic lipid leaflet is enriched in sphingomyelin, gangliosides such as GM-1 and GPI-anchored proteins. The cytoplasmic side of this membrane fraction is characteristically enriched by the raft marker proteins caveolin and flotillin. (c) Structure of the free sterols embedded in the mammalian sperm lipid bilayer. Cholesterol and desmosterol are both oriented with the hydrophilic head group (red circle) in the polar head group region of the phospholipid bilayer and with the hydrophobic part oriented parallel to the fatty acid moieties of the phospholipid bilayer (see panels a and b). Note that biophysical studies showed that, beyond the lower lipid bilayer stability and higher fluidity, the Ld phase is also more permeable to water when compared with the Lo phase,9394 which could be relevant for the cryopreservation of spermatozoa.
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Figure 1: Orientation of cholesterol and desmosterol in a lipid bilayer. (a) The lipid-disordered membrane phase contains low levels of cholesterol. The membrane is fluid and has high lateral diffusion characteristics. At 4°C this membrane fraction is solubilized by detergents (detergent soluble membrane fraction). Most transmembrane proteins fit into this membrane fraction because of their α-helix transmembrane domain(s). (b) The lipid ordered phase of a membrane is still fluid but is stabilized by high levels of cholesterol. At 4°C this membrane is not solubilized by detergents and proteins and lipids can be purified in a so-called detergent-resistant membrane fraction. The exoplasmic lipid leaflet is enriched in sphingomyelin, gangliosides such as GM-1 and GPI-anchored proteins. The cytoplasmic side of this membrane fraction is characteristically enriched by the raft marker proteins caveolin and flotillin. (c) Structure of the free sterols embedded in the mammalian sperm lipid bilayer. Cholesterol and desmosterol are both oriented with the hydrophilic head group (red circle) in the polar head group region of the phospholipid bilayer and with the hydrophobic part oriented parallel to the fatty acid moieties of the phospholipid bilayer (see panels a and b). Note that biophysical studies showed that, beyond the lower lipid bilayer stability and higher fluidity, the Ld phase is also more permeable to water when compared with the Lo phase,9394 which could be relevant for the cryopreservation of spermatozoa.

Mentions: It is important to understand membrane cholesterol modulations because the sperm plasma membrane underlies its form and function.2 Sterols are a vital component of the plasma membrane in eukaryotic, but not prokaryotic, cells. It is thought that cellular sterols evolved in eukaryotic life forms to allow higher order functioning of multi-protein complexes in regionalized membrane domains such as transporters, and channels.7 The dominant cellular sterol is cholesterol of which most (approximately 90%) is located in the plasma membrane.8 Here, cholesterol is found in its free form. For intracellular storage, cholesterol must be neutralized via esterification to a fatty acid and is then stored in lipid droplets with triacylglycerol.9 Mammalian spermatozoa do not carry lipid droplets, and thus essentially lack neutral lipids such as triacylglycerol and cholesteryl esters, but other sterol forms are present. The cholesterol precursor desmosterol (for structures see Figure 1) typically accounts for about 10% of total sterols and trace amounts of their sulfated forms are also reported such as cholesterol sulfate and desmosterol sulfate.10111213


New insights into the regulation of cholesterol efflux from the sperm membrane.

Leahy T, Gadella BM - Asian J. Androl. (2015 Jul-Aug)

Orientation of cholesterol and desmosterol in a lipid bilayer. (a) The lipid-disordered membrane phase contains low levels of cholesterol. The membrane is fluid and has high lateral diffusion characteristics. At 4°C this membrane fraction is solubilized by detergents (detergent soluble membrane fraction). Most transmembrane proteins fit into this membrane fraction because of their α-helix transmembrane domain(s). (b) The lipid ordered phase of a membrane is still fluid but is stabilized by high levels of cholesterol. At 4°C this membrane is not solubilized by detergents and proteins and lipids can be purified in a so-called detergent-resistant membrane fraction. The exoplasmic lipid leaflet is enriched in sphingomyelin, gangliosides such as GM-1 and GPI-anchored proteins. The cytoplasmic side of this membrane fraction is characteristically enriched by the raft marker proteins caveolin and flotillin. (c) Structure of the free sterols embedded in the mammalian sperm lipid bilayer. Cholesterol and desmosterol are both oriented with the hydrophilic head group (red circle) in the polar head group region of the phospholipid bilayer and with the hydrophobic part oriented parallel to the fatty acid moieties of the phospholipid bilayer (see panels a and b). Note that biophysical studies showed that, beyond the lower lipid bilayer stability and higher fluidity, the Ld phase is also more permeable to water when compared with the Lo phase,9394 which could be relevant for the cryopreservation of spermatozoa.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492045&req=5

Figure 1: Orientation of cholesterol and desmosterol in a lipid bilayer. (a) The lipid-disordered membrane phase contains low levels of cholesterol. The membrane is fluid and has high lateral diffusion characteristics. At 4°C this membrane fraction is solubilized by detergents (detergent soluble membrane fraction). Most transmembrane proteins fit into this membrane fraction because of their α-helix transmembrane domain(s). (b) The lipid ordered phase of a membrane is still fluid but is stabilized by high levels of cholesterol. At 4°C this membrane is not solubilized by detergents and proteins and lipids can be purified in a so-called detergent-resistant membrane fraction. The exoplasmic lipid leaflet is enriched in sphingomyelin, gangliosides such as GM-1 and GPI-anchored proteins. The cytoplasmic side of this membrane fraction is characteristically enriched by the raft marker proteins caveolin and flotillin. (c) Structure of the free sterols embedded in the mammalian sperm lipid bilayer. Cholesterol and desmosterol are both oriented with the hydrophilic head group (red circle) in the polar head group region of the phospholipid bilayer and with the hydrophobic part oriented parallel to the fatty acid moieties of the phospholipid bilayer (see panels a and b). Note that biophysical studies showed that, beyond the lower lipid bilayer stability and higher fluidity, the Ld phase is also more permeable to water when compared with the Lo phase,9394 which could be relevant for the cryopreservation of spermatozoa.
Mentions: It is important to understand membrane cholesterol modulations because the sperm plasma membrane underlies its form and function.2 Sterols are a vital component of the plasma membrane in eukaryotic, but not prokaryotic, cells. It is thought that cellular sterols evolved in eukaryotic life forms to allow higher order functioning of multi-protein complexes in regionalized membrane domains such as transporters, and channels.7 The dominant cellular sterol is cholesterol of which most (approximately 90%) is located in the plasma membrane.8 Here, cholesterol is found in its free form. For intracellular storage, cholesterol must be neutralized via esterification to a fatty acid and is then stored in lipid droplets with triacylglycerol.9 Mammalian spermatozoa do not carry lipid droplets, and thus essentially lack neutral lipids such as triacylglycerol and cholesteryl esters, but other sterol forms are present. The cholesterol precursor desmosterol (for structures see Figure 1) typically accounts for about 10% of total sterols and trace amounts of their sulfated forms are also reported such as cholesterol sulfate and desmosterol sulfate.10111213

Bottom Line: How does a hydrophobic cholesterol molecule inserted in the sperm plasma membrane enter the energetically unfavorable aqueous surroundings?The overall aim is to better understand cholesterol redistribution in the sperm plasma membrane, its relation to the possible activation of a cholesterol transporter and the role of cholesterol acceptors.Armed with such knowledge, sperm handling techniques can be adapted to better prepare spermatozoa for in vitro and in vivo fertilization.

View Article: PubMed Central - PubMed

Affiliation: Department of Farm Animal Health and of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 2, 3584 CM Utrecht, The Netherlands.

ABSTRACT
Cholesterol is an essential component of the mammalian plasma membrane because it promotes membrane stability without comprising membrane fluidity. Given this important cellular role, cholesterol levels are tightly controlled at multiple levels. It has been clearly shown that cholesterol redistribution and depletion from the sperm membrane is a key part of the spermatozoon's preparation for fertilization. Some factors that regulate these events are described (e.g., bicarbonate, calcium) but the mechanisms underlying cholesterol export are poorly understood. How does a hydrophobic cholesterol molecule inserted in the sperm plasma membrane enter the energetically unfavorable aqueous surroundings? This review will provide an overview of knowledge in this area and highlight our gaps in understanding. The overall aim is to better understand cholesterol redistribution in the sperm plasma membrane, its relation to the possible activation of a cholesterol transporter and the role of cholesterol acceptors. Armed with such knowledge, sperm handling techniques can be adapted to better prepare spermatozoa for in vitro and in vivo fertilization.

No MeSH data available.