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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.


Formation of oxysterols during capacitation might enhance sperm reverse cholesterol transport. (a) Cholesterol is oriented in a parallel position to fatty acids and deeply embedded in both leaflets of the phospholipid bilayer. (b) Because of the additional hydroxyl groups of peroxidized cholesterol, the formed oxysterol no longer favors the original orientation of the parent cholesterol. Instead, it will line up the two (or three) hydroxyl groups (or derivatives thereof) in parallel with the phospholipid head groups. By doing this, the oxysterols might facilitate the transport of cholesterol either by activating the transporter directly or by lifting neighboring cholesterol partly out of the phospholipid layer91 where it is more accessible to sterol carriers (not depicted in this diagram: see Figures 2 and 3). The formation of oxysterols in the sperm membrane is dependent on bicarbonate and reactive oxygen species and can be prevented by antioxidants (Vitamin A or E). (c) Metabolic routes for the oxysterol formation in spermatozoa. The hydroxyl groups and derivatives thereof are indicated as red circles.
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Figure 4: Formation of oxysterols during capacitation might enhance sperm reverse cholesterol transport. (a) Cholesterol is oriented in a parallel position to fatty acids and deeply embedded in both leaflets of the phospholipid bilayer. (b) Because of the additional hydroxyl groups of peroxidized cholesterol, the formed oxysterol no longer favors the original orientation of the parent cholesterol. Instead, it will line up the two (or three) hydroxyl groups (or derivatives thereof) in parallel with the phospholipid head groups. By doing this, the oxysterols might facilitate the transport of cholesterol either by activating the transporter directly or by lifting neighboring cholesterol partly out of the phospholipid layer91 where it is more accessible to sterol carriers (not depicted in this diagram: see Figures 2 and 3). The formation of oxysterols in the sperm membrane is dependent on bicarbonate and reactive oxygen species and can be prevented by antioxidants (Vitamin A or E). (c) Metabolic routes for the oxysterol formation in spermatozoa. The hydroxyl groups and derivatives thereof are indicated as red circles.

Mentions: In other cell types, the formation of trace amounts of oxysterols is reported to facilitate RCT by regulating cholesterol availability in the membrane environment:89909192 for model see Figure 4. It is possible that bicarbonate induction of the oxysterol formation facilitates cholesterol efflux from sperm by one of these means. Interestingly, despite the more hydrophilic properties of oxysterols and their surface orientation they are not preferentially picked up by FAF-albumin under capacitation conditions when compared with cholesterol and desmosterol.10


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

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

Formation of oxysterols during capacitation might enhance sperm reverse cholesterol transport. (a) Cholesterol is oriented in a parallel position to fatty acids and deeply embedded in both leaflets of the phospholipid bilayer. (b) Because of the additional hydroxyl groups of peroxidized cholesterol, the formed oxysterol no longer favors the original orientation of the parent cholesterol. Instead, it will line up the two (or three) hydroxyl groups (or derivatives thereof) in parallel with the phospholipid head groups. By doing this, the oxysterols might facilitate the transport of cholesterol either by activating the transporter directly or by lifting neighboring cholesterol partly out of the phospholipid layer91 where it is more accessible to sterol carriers (not depicted in this diagram: see Figures 2 and 3). The formation of oxysterols in the sperm membrane is dependent on bicarbonate and reactive oxygen species and can be prevented by antioxidants (Vitamin A or E). (c) Metabolic routes for the oxysterol formation in spermatozoa. The hydroxyl groups and derivatives thereof are indicated as red circles.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Formation of oxysterols during capacitation might enhance sperm reverse cholesterol transport. (a) Cholesterol is oriented in a parallel position to fatty acids and deeply embedded in both leaflets of the phospholipid bilayer. (b) Because of the additional hydroxyl groups of peroxidized cholesterol, the formed oxysterol no longer favors the original orientation of the parent cholesterol. Instead, it will line up the two (or three) hydroxyl groups (or derivatives thereof) in parallel with the phospholipid head groups. By doing this, the oxysterols might facilitate the transport of cholesterol either by activating the transporter directly or by lifting neighboring cholesterol partly out of the phospholipid layer91 where it is more accessible to sterol carriers (not depicted in this diagram: see Figures 2 and 3). The formation of oxysterols in the sperm membrane is dependent on bicarbonate and reactive oxygen species and can be prevented by antioxidants (Vitamin A or E). (c) Metabolic routes for the oxysterol formation in spermatozoa. The hydroxyl groups and derivatives thereof are indicated as red circles.
Mentions: In other cell types, the formation of trace amounts of oxysterols is reported to facilitate RCT by regulating cholesterol availability in the membrane environment:89909192 for model see Figure 4. It is possible that bicarbonate induction of the oxysterol formation facilitates cholesterol efflux from sperm by one of these means. Interestingly, despite the more hydrophilic properties of oxysterols and their surface orientation they are not preferentially picked up by FAF-albumin under capacitation conditions when compared with cholesterol and desmosterol.10

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.