Limits...
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.


Related in: MedlinePlus

Redistribution of proteins and lipids of the sperm membrane during capacitation. (a) Lateral redistribution of cholesterol, seminolipid and partial exposure of phosphatidylethanolamine (PE) and phosphatidylserine (PS) are driven by calcium and bicarbonate ions. The nonresponsive cells are m540 negative and have lipids oriented as depicted in the sperm cartoon on the left. The responsive cells show high m540 fluorescence, a migration of seminolipid to the equatorial region, and a concentration of cholesterol in the apical area. At the apical region, a partial scrambling of PS and PE also takes place (as depicted in the middle spermatozoon). Only these responsive cells are prone to cholesterol efflux in the presence of fatty acid free-albumin and cause a loss of filipin staining as depicted in the cartoon on the right.22 (b) Capacitation is completed by the aggregation of membrane rafts in the apical ridge of the sperm head. This area also shows the formation of a trans-Soluble NSF Attachment REceptor protein complex, which facilitates the fusion of the outer acrosomal membrane to the sperm plasma membrane and the formation of a zona-binding protein complex.55
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4492045&req=5

Figure 2: Redistribution of proteins and lipids of the sperm membrane during capacitation. (a) Lateral redistribution of cholesterol, seminolipid and partial exposure of phosphatidylethanolamine (PE) and phosphatidylserine (PS) are driven by calcium and bicarbonate ions. The nonresponsive cells are m540 negative and have lipids oriented as depicted in the sperm cartoon on the left. The responsive cells show high m540 fluorescence, a migration of seminolipid to the equatorial region, and a concentration of cholesterol in the apical area. At the apical region, a partial scrambling of PS and PE also takes place (as depicted in the middle spermatozoon). Only these responsive cells are prone to cholesterol efflux in the presence of fatty acid free-albumin and cause a loss of filipin staining as depicted in the cartoon on the right.22 (b) Capacitation is completed by the aggregation of membrane rafts in the apical ridge of the sperm head. This area also shows the formation of a trans-Soluble NSF Attachment REceptor protein complex, which facilitates the fusion of the outer acrosomal membrane to the sperm plasma membrane and the formation of a zona-binding protein complex.55

Mentions: Bicarbonate and Ca2+ drive the lateral redistribution of sperm membrane lipids and proteins. In the lipid arena, this involves an enrichment of cholesterol in the apical region of the sperm head. It is here that cholesterol is exported from the sperm membrane to cholesterol acceptors in the extracellular fluid (e.g., FAF albumin). Bicarbonate has been shown to be a key effector of this efflux process because in its absence cholesterol levels are unaltered by FAF albumin. Cholesterol redistribution is driven by the bicarbonate dependent activation of cAMP production (by adenylate cyclase) and by a cAMP-dependent protein kinase A (PKA). Concomitant with the lateral translocation of sperm membrane sterols from the equatorial region of the sperm head to the apical ridge22 is the partial scrambling of the phospholipids phosphatidylethanolamine (PE) and phosphatidylserine (PS) in the same region, and the opposing retrograde movement of seminolipid (a sperm specific glycolipid) from the apical area to the equator.2324 These phenomena are independent of free radical induced apoptosis-like exposure of PS (commonly detected using annexin-V probes) at the mid-piece.25 The exposure of PE at the sperm surface allows intercalation of the fluorescent probe m540 because this membrane type displays higher fluidity.26 It is only after activation of this pathway and the resulting lateral remodeling of the sperm membrane lipids (see Figure 2a) that FAF albumin can specifically take up cholesterol (and desmosterol) from the sperm surface.102227


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

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

Redistribution of proteins and lipids of the sperm membrane during capacitation. (a) Lateral redistribution of cholesterol, seminolipid and partial exposure of phosphatidylethanolamine (PE) and phosphatidylserine (PS) are driven by calcium and bicarbonate ions. The nonresponsive cells are m540 negative and have lipids oriented as depicted in the sperm cartoon on the left. The responsive cells show high m540 fluorescence, a migration of seminolipid to the equatorial region, and a concentration of cholesterol in the apical area. At the apical region, a partial scrambling of PS and PE also takes place (as depicted in the middle spermatozoon). Only these responsive cells are prone to cholesterol efflux in the presence of fatty acid free-albumin and cause a loss of filipin staining as depicted in the cartoon on the right.22 (b) Capacitation is completed by the aggregation of membrane rafts in the apical ridge of the sperm head. This area also shows the formation of a trans-Soluble NSF Attachment REceptor protein complex, which facilitates the fusion of the outer acrosomal membrane to the sperm plasma membrane and the formation of a zona-binding protein complex.55
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Redistribution of proteins and lipids of the sperm membrane during capacitation. (a) Lateral redistribution of cholesterol, seminolipid and partial exposure of phosphatidylethanolamine (PE) and phosphatidylserine (PS) are driven by calcium and bicarbonate ions. The nonresponsive cells are m540 negative and have lipids oriented as depicted in the sperm cartoon on the left. The responsive cells show high m540 fluorescence, a migration of seminolipid to the equatorial region, and a concentration of cholesterol in the apical area. At the apical region, a partial scrambling of PS and PE also takes place (as depicted in the middle spermatozoon). Only these responsive cells are prone to cholesterol efflux in the presence of fatty acid free-albumin and cause a loss of filipin staining as depicted in the cartoon on the right.22 (b) Capacitation is completed by the aggregation of membrane rafts in the apical ridge of the sperm head. This area also shows the formation of a trans-Soluble NSF Attachment REceptor protein complex, which facilitates the fusion of the outer acrosomal membrane to the sperm plasma membrane and the formation of a zona-binding protein complex.55
Mentions: Bicarbonate and Ca2+ drive the lateral redistribution of sperm membrane lipids and proteins. In the lipid arena, this involves an enrichment of cholesterol in the apical region of the sperm head. It is here that cholesterol is exported from the sperm membrane to cholesterol acceptors in the extracellular fluid (e.g., FAF albumin). Bicarbonate has been shown to be a key effector of this efflux process because in its absence cholesterol levels are unaltered by FAF albumin. Cholesterol redistribution is driven by the bicarbonate dependent activation of cAMP production (by adenylate cyclase) and by a cAMP-dependent protein kinase A (PKA). Concomitant with the lateral translocation of sperm membrane sterols from the equatorial region of the sperm head to the apical ridge22 is the partial scrambling of the phospholipids phosphatidylethanolamine (PE) and phosphatidylserine (PS) in the same region, and the opposing retrograde movement of seminolipid (a sperm specific glycolipid) from the apical area to the equator.2324 These phenomena are independent of free radical induced apoptosis-like exposure of PS (commonly detected using annexin-V probes) at the mid-piece.25 The exposure of PE at the sperm surface allows intercalation of the fluorescent probe m540 because this membrane type displays higher fluidity.26 It is only after activation of this pathway and the resulting lateral remodeling of the sperm membrane lipids (see Figure 2a) that FAF albumin can specifically take up cholesterol (and desmosterol) from the sperm surface.102227

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.


Related in: MedlinePlus