Ovarian cholesterol efflux: ATP-binding cassette transporters and follicular fluid HDL regulate cholesterol content in mouse oocytes

Alonso Quiroz, Paz Molina, Nicolás Santander, Daniel Gallardo, Attilio Rigotti, Dolores Busso*

*Autor correspondiente de este trabajo

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

7 Citas (Scopus)

Resumen

High density lipoproteins (HDL) take up cholesterol from peripheral tissues via ABC transporters and deliver it to the liver via scavenger receptor class B type I (SR-B1). HDL are the main lipoproteins present in follicular fluid (FF). They are thought to derive from plasma, but their origin is still controversial. SR-B1 knock-out (KO) mice have provided important evidence linking HDL metabolism and female fertility. These mice have cholesterol-rich circulating HDL and female infertility that can be restored by treating mice with the cholesterol-lowering drug probucol. Ovulated oocytes from SR-B1 KO females are dysfunctional and show excess cholesterol. The mechanisms explaining the contribution of FF HDL to oocyte cholesterol homeostasis are unknown. Here, using quantitation of filipin fluorescence we show that in SR-B1 KO ovaries, cholesterol excess is first observed in immature oocytes in antral follicles. By performing cross-transplant experiments between WT and apolipoprotein A-I deficient (ApoA-I KO) mice, which lack the main protein component of HDL, we provide evidence supporting the plasmatic origin of FF HDL. Also, we demonstrate that probucol treatment in SR-B1 KO females results in lowering of cholesterol content in their oocytes. Incubation of oocytes from SR-B1 KO mice with purified WT HDL reduces their cholesterol content, suggesting that HDL promote efflux of excess cholesterol from oocytes. In agreement with this hypothesis, we identified ABC transporters in oocytes and observed that ABCA1 KO oocytes have excess cholesterol and lower viability than WT oocytes.

Idioma originalInglés
Páginas (desde-hasta)348-361
Número de páginas14
PublicaciónBiology of Reproduction
Volumen102
N.º2
DOI
EstadoPublicada - 14 feb. 2020
Publicado de forma externa

Nota bibliográfica

Publisher Copyright:
© 2019 The Author(s). Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved.

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