Effects of hepatic expression of the high-density lipoprotein receptor SR-BI on lipoprotein metabolism and female fertility

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dc.contributor.authorYesilaltay, A
dc.contributor.authorMorales, MG
dc.contributor.authorAmigo, L
dc.contributor.authorZanlungo, S
dc.contributor.authorRigotti, A
dc.contributor.authorKarackattu, SL
dc.contributor.authorDonahee, MH
dc.contributor.authorKozarsky, KF
dc.contributor.authorKrieger, M
dc.date.accessioned2024-01-10T12:38:36Z
dc.date.available2024-01-10T12:38:36Z
dc.date.issued2006
dc.description.abstractThe etiology of human female infertility is often uncertain. The sterility of high-density lipoprotein (HDL) receptor-negative (SR-BI-/-) female mice suggests a link between female infertility and abnormal lipoprotein metabolism. SR-BI-/- mice exhibit elevated plasma total cholesterol [ with normalsized and abnormally large HDL and high unesterified to total plasma cholesterol (UC:TC) ratio]. We explored the influence of hepatic SR-BI on female fertility by inducing hepatic SR-BI expression in SR-BI-/- animals by adenovirus transduction or stable transgenesis. For transgenes, we used both wild-type SR-BI and a double-point mutant, Q402R/Q418R (SR-BI-RR), which is unable to bind to and mediate lipid transfer from wild-type HDL normally, but retains virtually normal lipid transport activities with low-density lipoprotein. Essentially wild-type levels of hepatic SR-BI expression in SR-BI-/- mice restored to nearly normal the HDL size distribution and plasma UC: TC ratio, whereas approximately 7- to 40- fold overexpression dramatically lowered plasma TC and increased biliary cholesterol secretion. In contrast, SR-BI-RR overexpression had little effect on SR-BI-/- mice, but in SR-BI-/- mice, it substantially reduced levels of abnormally large HDL and normalized the UC: TC ratio. In all cases, hepatic transgenic expression restored female fertility. Overexpression in SR-BI-/- mice of lecithin: cholesterol acyl transferase, which esterifies plasma HDL cholesterol, did not normalize the UC: TC ratio, probably because the abnormal HDL was a poor substrate, and did not restore fertility. Thus, hepatic SR- BImediated lipoprotein metabolism influences murine female fertility, raising the possibility that dyslipidemia might contribute to human female infertility and that targeting lipoprotein metabolism might complement current assisted reproductive technologies.
dc.description.funderFOGARTY INTERNATIONAL CENTER
dc.description.funderNATIONAL HEART, LUNG, AND BLOOD INSTITUTE
dc.description.funderFIC NIH HHS
dc.description.funderNHLBI NIH HHS
dc.fechaingreso.objetodigital2024-05-15
dc.format.extent12 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1210/en.2005-1286
dc.identifier.eissn1945-7170
dc.identifier.issn0013-7227
dc.identifier.pubmedidMEDLINE:16410302
dc.identifier.urihttps://doi.org/10.1210/en.2005-1286
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/77070
dc.identifier.wosidWOS:000236045000002
dc.information.autorucMedicina;Rigotti A;S/I;68489
dc.information.autorucMedicina;Zanlungo S;S/I;72650
dc.issue.numero4
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final1588
dc.pagina.inicio1577
dc.publisherENDOCRINE SOC
dc.revistaENDOCRINOLOGY
dc.rightsacceso restringido
dc.subjectAPOLIPOPROTEIN-A-I
dc.subjectLECITHIN-CHOLESTEROL ACYLTRANSFERASE
dc.subjectCORONARY-HEART-DISEASE
dc.subjectFOLLICULAR-FLUID LIPOPROTEINS
dc.subjectSCAVENGER RECEPTOR
dc.subjectTRANSGENIC MICE
dc.subjectTARGETED DISRUPTION
dc.subjectDEFICIENT MICE
dc.subjectCARDIAC DYSFUNCTION
dc.subjectLIPID-METABOLISM
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleEffects of hepatic expression of the high-density lipoprotein receptor SR-BI on lipoprotein metabolism and female fertility
dc.typeartículo
dc.volumen147
sipa.codpersvinculados68489
sipa.codpersvinculados72650
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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