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

Abstract

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.

Comparative Transcriptome Profiling of mRNA and lncRNA of Ovaries in High and Low Egg Production Performance in Domestic Pigeons (Columba livia)

“…The results showed that both of these lncRNAs and mRNAs were involved in the regulation of ATP binding, protein binding, cell differentiation and transcription by RNA polymerase II. For example, ATP binding has been shown to be involved in the regulation of oocyte formation (Quiroz et al, 2020). The RNA polymerase II involved in a combinatorial control of the timely regulated Spo11 splicing during the process of meiosis (Cesari et al, 2020).…”

Lipid Metabolic Process Involved in Oocyte Maturation During Folliculogenesis

“…Lipid metabolism disorders including a high plasma cholesterol level and high nonesterified cholesterol level in the extraovarian environment account for the infertility phenotype of Scarb1 -deficient ( Scarb1 −/− ) mice. When altering the structure or quantity of abnormal HDL by silencing the ApoA1 gene or lowering cholesterol levels in blood by feeding probucol, the fertility of Scarb1 -deficient mice was partially or completely restored ( Miettinen et al, 2001 ; Quiroz et al, 2020 ). Human plasma cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from HDL and LDL to VLDL, which in turn binds hepatic LDL receptor (LDLR) or VLDL receptor (VLDLR) to transport cholesterol from peripheral tissues to the liver (reverse cholesterol transport).…”

Mechanisms of Oogenesis-Related Long Non-coding RNAs in Porcine Ovaries Treated With Recombinant Pig Follicle-Stimulating Hormone

“…The results revealed that both of these DE mRNAs and DE lncRNAs were participated in the regulation of protein binding, ATP binding, cell differentiation, and transcription by RNA polymerase II. It can be illustrated that ATP binding has been reported to participate in the oogenesis regulation ( 34 ). The RNA polymerase II was reported to be involved in the combinatorial control of Spo11 splicing, which is timely regulated during meiosis ( 35 ).…”